HK1161292A

HK1161292A - Isoprene synthase variants for improved microbial production of isoprene

Info

Publication number: HK1161292A
Application number: HK12101541.8A
Authority: HK
Inventors: Marguerite A. Cervin; Gregory M. Whited; Andrei Miasnikov; Caroline M. Peres; Walter Weyler; Derek H. Wells; Richard R. Bott; Christopher Lee. Rife; Joseph C. Mcauliffe; James Kellis
Original assignee: Danisco Us Inc.; The Goodyear Tire & Rubber Company
Priority date: 2008-04-23
Filing date: 2009-04-23
Publication date: 2012-08-24

Description

Isoprene synthase variants for improved microbial production of isoprene

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. provisional application serial No. 61/125,336, filed on 23/4/2008, which is incorporated herein by reference in its entirety.

Technical Field

The present invention provides methods and compositions comprising at least one isoprene synthase enzyme with improved catalytic activity and/or solubility. In particular, the invention provides variant plant isoprene synthases for increasing isoprene production in microbial host cells. The biosynthetically produced isoprenes of the present invention are useful in the manufacture of rubbers and elastomers.

Background

Isoprenoids are isoprene polymers used in pharmaceutical, nutraceutical, flavoring, fragrance and rubber products. However, the natural isoprenoid supply is limited due to ecological concerns. For this reason and in order to provide isoprenoid compositions with fewer impurities and greater homogeneity, isoprenoids, such as rubbers, are often synthetically produced.

Isoprene (2-methyl-1, 3-butadiene) is a volatile hydrocarbon that is insoluble in water and soluble in alcohol. Commercially viable amounts of isoprene can be obtained by direct separation from the petroleum C5 cracked fraction or by dehydration of C5 isoalkanes or isoolefins (Weisselmel and Arpe, Industrial Organic Chemistry, 4 th edition, Wiley-VCH, pp. 117-122, 2003). The C5 backbone can also be synthesized from smaller subunits. However, it would be desirable to have a commercially viable process for producing isoprene that does not rely on non-renewable resources.

Biosynthetic production of isoprene occurs via two different metabolic pathways (Julising et al, Appl Microbiol Biotechnol, 75: 1377-1384, 2007). In eukaryotes and archaea (archae), isoprene is formed via the Mevalonate (MVA) pathway, while some eubacteria and higher plants produce isoprene via the methylerythritol phosphate (MEP) pathway. The emission of isoprene from plants is light and temperature dependent, and its increase is associated with leaf development. The enzyme producing isoprene (isoprene synthase) has been identified in trees of the genus Populus (Aspen) (Silver and Fall, Plant Physiol, 97: 1588-. Bacterial production of isoprene has also been described (Kuzma et al, Curr Microbiol, 30: 97-103, 1995; and Wilkins, Chemosphere, 32: 1427-. However, the levels of isoprene obtainable by the bacterial systems of the prior art are not sufficient for commercial use.

Thus, what is needed in the art is an efficient, large-scale, bacterial isoprene production process that provides a starting material for the manufacture of isoprenoids.

All patents, patent applications, articles and publications mentioned herein are expressly incorporated herein by reference.

Summary of The Invention

The present invention provides methods and compositions comprising at least one isoprene synthase enzyme with improved catalytic activity and/or solubility. In particular, the invention provides plant variant isoprene synthases for increasing isoprene production in microbial host cells. The biosynthetically produced isoprenes of the present invention are useful in the manufacture of rubbers and elastomers.

Specifically, the present invention provides isolated isoprene synthase variants comprising substitutions at positions corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues of pueraria isoprene synthase comprising the amino acid sequence of SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the isoprene synthase variant is a Pueraria species (Pueraria sp.) isoprene synthase variant or a poplar (Populus species (Populus sp.) isoprene synthase variant in some embodiments, the one or more residues are selected from, but not limited to, the group consisting of L26, E30, F31, Q33, L35, E36, N37, L39, K40, V41, K43, L44, R61, V62, D63, Q65, K87, E94, N95, L99, D100, N105, K137, E138, G143, E144, N182, L184, K185, G187, N189, T190, P225, H226, K247, T257, E258, M392, D392, N334, D353, S358, I I, I58398, G187, N189, T190, P225, H226, K259, K247, T533, Q4726, Q4753, Q53, Q4753, Q47, N25, Y309, D310, L377, F381, E384, Y399, N402, a403, S406, S407, G409, a411, L413, F449, a456, T457, S458, a459, a460, E461, L462, E463, R464, G465, E466, T467, T468, N469, M523, S527, and Y531. In some embodiments, the one or more residues are selected from the group consisting of, but not limited to, a20, N21, Y22, Q23, R271, W278, F299, V302, and S408. The present invention also provides isolated isoprene synthase variants having an a20G substitution in kudzu isoprene synthase having the amino acid sequence of SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In a subset of these embodiments, the variant comprises at least two substitutions (2, 3, 4, 5, 6, 7, 8, 9, or 10), wherein one of the substitutions is a polypeptide having the amino acid sequence of SEQ ID NO: 2, a20G substitution in pueraria isoprene synthase. The present invention also provides isolated isoprene synthase variants having the S408D substitution in kudzu isoprene synthase having the amino acid sequence of SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In a subset of these embodiments, the variant comprises at least two substitutions (2, 3, 4, 5, 6, 7, 8, 9, or 10), wherein one of the substitutions is a polypeptide having the amino acid sequence of SEQ ID NO: 2, or a substitution of S408D in pueraria isoprene synthase. In some preferred embodiments, the isoprene synthase variants have at least one improved property compared to wild-type isoprene synthase. In some particularly preferred embodiments, the at least one improved property is selected from, but not limited to, the group consisting of specific activity (production of isoprene from dimethylallyl diphosphate) and solubility.

In addition, the present invention also provides a polynucleotide sequence encoding the isoprene synthase variant. Also provided are expression vectors comprising a polynucleotide sequence encoding the isoprene synthase variant operably linked to a promoter. In other embodiments, the invention provides host cells comprising the expression vectors. Also provided is a lysate of the host cell, wherein the lysate further comprises lysozyme. In some embodiments, the lysate has a neutral pH (6.5 to 7.5), while in other embodiments, the lysate has a basic pH (above 7.5 and below 9.5). The present invention also provides a method of producing isoprene, comprising: (a) providing a host cell comprising the expression vector; and (b) culturing the host cell under conditions suitable for the production of isoprene. In some embodiments, the method further comprises (c) recovering the isoprene. In still other embodiments, the method further comprises (d) polymerizing the isoprene. The present invention also provides a method for detecting isoprene synthase activity, comprising: (a) culturing a host cell comprising the expression vector under conditions suitable for production of the isoprene synthase variant; (b) lysing the host cells with a lysis buffer comprising lysozyme to produce a cell lysate; and (c) detecting isoprene synthase activity in the cell lysate by measuring isoprene production from dimethylallyl Diphosphate (DMAPP). In some embodiments, the host is selected from the group consisting of, but not limited to, gram-positive bacterial cells, gram-negative bacterial cells, filamentous fungal cells, and yeast cells. In some preferred embodiments, the host is selected from the group consisting of, but not limited to, Escherichia species (e.col), pantoea species (pantoa sp.) (p.citrea), Bacillus species (Bacillus sp.) (Bacillus subtilis), Yarrowia species (Yarrowia sp.) (Yarrowia lipolytica), and Trichoderma (Trichoderma reesei). In some embodiments, the host cell is cultured in a medium comprising a carbon source selected from the group consisting of glucose, glycerol, dihydroxyacetone, yeast extract, biomass, molasses, sucrose and oil.

In addition, the present invention provides a method for detecting isoprene in a plurality of samples (high throughput screening method) comprising: (a) providing: i) a plurality of samples each comprising isoprene synthase; ii) a glass plate comprising a plurality of wells; and iii) a cover for the glass plate; (b) placing multiple samples in multiple wells of the glass plate; (c) sealing the glass plate with a cover to produce a sealed glass plate having a headspace associated with the sample in each of the plurality of wells; (d) incubating the glass plate under conditions in which isoprene synthase is active; (e) isoprene in the headspace was detected. In some embodiments, isoprene is detected by gas chromatography-mass spectrometry (GC-MS). In some embodiments, the plurality of samples comprises host cells comprising an expression vector comprising a polynucleotide sequence encoding an isoprene synthase variant operably linked to a promoter. In some embodiments, the multiple samples comprise host cell lysate, lysozyme, and dimethylallyl Diphosphate (DMAPP). In some preferred embodiments, the glass sheet is a deep hole glass block. In some preferred embodiments, the plurality of wells comprises at least 24 wells (preferably at least 48 wells, more preferably at least 96 wells, still more preferably at least 192 wells, and most preferably at least 384 wells). In a particularly preferred embodiment, the plurality of wells each comprise a volume comprising 2ml or less (preferably 2ml to 0.2 ml).

Additionally, the present invention provides a host cell comprising a heterologous polynucleotide sequence encoding an isoprene synthase variant operably linked to a promoter, wherein the isoprene synthase variant comprises a substitution at a position corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues of pueraria isoprene synthase comprising the amino acid sequence of SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In some embodiments, the one or more residues are selected from, but not limited to, the group consisting of L26, E30, F31, Q33, L35, E36, N37, L39, K40, V41, K43, L44, R61, V62, D63, Q65, K87, E94, N95, L99, D100, N105, K137, E138, G143, E144, N182, L184, K185, G187, N189, T190, P225, H226, K247, T257, E258, M259, D266, N334, D353, S358, I358I, E361, N389, I392, I393, K398, E401, C421, Q423, Q424, E425, D426, H430, L432, R433, S434, D437, R533, L4727, L2, R543, L2, R478, L47478, L2, R478, L2, L47478, L2, L53, L, and P478. In some embodiments, the one or more residues are selected from the group consisting of, but not limited to, P24, N25, Y309, D310, L377, F381, E384, Y399, N402, a403, S406, S407, G409, a411, L413, F449, a456, T457, S458, a459, a460, E461, L462, E463, R464, G465, E466, T467, T468, N469, M523, S527, and Y531. In some embodiments, the one or more residues are selected from the group consisting of, but not limited to, a20, N21, Y22, Q23, R271, W278, F299, V302, and S408. The present invention also provides isolated isoprene synthase variants having an a20G substitution and/or an S408D substitution in a pueraria isoprene synthase having the amino acid sequence of SEQ ID NO: 2, or a pharmaceutically acceptable salt thereof. In some preferred embodiments, the isoprene synthase variants have at least one improved property compared to wild-type isoprene synthase. In some particularly preferred embodiments, the at least one improved property is selected from, but not limited to, the group consisting of specific activity (production of isoprene from dimethylallyl diphosphate) and solubility. In some preferred embodiments, the polynucleotide sequence is contained within a plasmid. In other preferred embodiments, the polynucleotide sequence is integrated into the chromosome of the host cell. In some embodiments, the host is selected from the group consisting of, but not limited to, gram-positive bacterial cells, gram-negative bacterial cells, filamentous fungal cells, and yeast cells. In some preferred embodiments, the host is selected from the group consisting of, but not limited to, Escherichia species (e.coli), pantoea species (pantoa sp.) (p.citrea), Bacillus species (Bacillus sp.) (Bacillus subtilis), Yarrowia species (Yarrowia sp.) (Yarrowia lipolytica), and Trichoderma (Trichoderma reesei). In some embodiments, the host cell is cultured in a medium comprising a carbon source selected from the group consisting of glucose, glycerol, dihydroxyacetone, yeast extract, biomass, molasses, sucrose and oil. In some embodiments, the host cell further comprises a heterologous or native nucleic acid encoding an IDI polypeptide and/or a heterologous or native nucleic acid encoding a DXS polypeptide, sometimes in combination with the native DXP pathway (e.g., DXS and IDI are expressed in e. Alternatively, the entire DXP pathway (fig. 15) may be expressed on a plasmid or integrated on the chromosome as an operon with a single promoter regulating expression or multiple promoters regulating the different strengths of one or more of the individual genes (e.g., GI 1.20, GI 1.5, or GI 1.6). In some embodiments, the host cell further comprises one or more nucleic acids encoding an IDI polypeptide and a DXS polypeptide, while in some preferred embodiments, one vector encodes the isoprene synthase variant, the IDI polypeptide, and the DXS polypeptide. In some embodiments, the host cell further comprises a heterologous nucleic acid encoding a MVA pathway polypeptide, such as a MVA pathway polypeptide from Saccharomyces cerevisiae (Saccharomyces cerevisiae) or Enterococcus faecalis (Enterococcus faecalis). In some embodiments, the host cell further comprises one or more nucleic acids encoding a MVA pathway polypeptide and a DXS polypeptide, while in some preferred embodiments, one vector encodes the isoprene synthase variant, the MVA pathway polypeptide, and the DXS polypeptide. In some preferred embodiments, the host cell further comprises one or more nucleic acids encoding a DXS polypeptide, an IDI polypeptide, or one or more of the remaining DXP pathway polypeptides and an MVA pathway polypeptide. In some embodiments, the vector further comprises a selectable marker (e.g., an antibiotic resistance nucleic acid). Also provided are methods of producing isoprene, comprising: (a) culturing the host cell under suitable culture conditions for producing isoprene; and (b) producing isoprene. In some embodiments, the method further comprises (c) recovering the isoprene. In some preferred embodiments, the method further comprises (d) polymerizing the isoprene. The present invention also provides a method of producing isoprene synthase, comprising: (a) providing: (i) a host cell; and (ii) a nucleic acid encoding an isoprene synthase variant operably linked to a promoter, wherein the isoprene synthase variant comprises a substitution at a position corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues of pueraria lobata isoprene synthase comprising the amino acid sequence of SEQ ID NO: 2;

(b) Contacting a host cell with the nucleic acid to produce a transformed host cell; and (c) culturing the transformed host cell under suitable culture conditions for the production of isoprene synthase.

In another aspect, the present invention provides isolated poplar isoprene synthase variants. In one embodiment, the variant comprises a truncation in the amino-terminal portion of isoprene synthase. In another embodiment, the isoprene synthase variant has increased specific activity compared to a full-length isoprene synthase. In another embodiment, the isoprene synthase is SEQ ID NO: poplar isoprene synthase of 120. In another embodiment, the variant is selected from the group consisting of MEA variant (SEQ ID NO: 122), MSV variant (SEQ ID NO: 124), MVS variant (SEQ ID NO: 126), MTE variant (SEQ ID NO: 128), MNV variant (SEQ ID NO: 130). In another embodiment, the variant is an MEA variant (SEQ ID NO: 122). In another embodiment, the variant is selected from the group consisting of a TRC (-3) variant (SEQ ID NO: 136), a TRC (-4) variant (SEQ ID NO: 138), a TRC (-5) variant (SEQ ID NO: 140), a TRC (-6) variant (SEQ ID NO: 142), and a TRC (-7) variant (SEQ ID NO: 144). In another embodiment, the variant is a MET variant of Populus tremuloides isoprene synthase (SEQ ID NO: 146). In another embodiment, the variant is a MET variant of Populus tomentosa (P.trichocharpa) isoprene synthase (SEQ ID NO: 148).

In another aspect, the present invention provides an isolated poplar isoprene synthase variant, wherein the variant comprises a substitution of one or more amino acid residues of a wild-type isoprene synthase; and wherein the isoprene synthase variant has increased isoprene synthase activity compared to a wild-type isoprene synthase. In one embodiment, the increased isoprene synthase activity is exhibited by a host cell comprising an isoprene synthase variant that grows at a faster rate in the presence of dimethylallyl pyrophosphate (DMAPP) as compared to a host cell comprising a parent isoprene synthase. In another embodiment, the isoprene synthase is SEQ ID NO: poplar isoprene synthase of 120. In another embodiment, the variant comprises one of the amino acid substitutions selected from the group consisting of V10M, F12S, T15A, E18G, V58I, V58F, L70Q, L70V, T71V, V79V, E89V, G94V, S119V, F120V, G127V, E175V, T212V, S257V, R262V, a 266V, F280V, N297V, F305V, L319V, E323V, a 328V, D342V, a 359V, K366V, E368V, L374V, S396V, V418V, K438V, H440V, T36442, I V, a 36449V, K4672, K V, N507V, N507V, N. In another embodiment, the at least one amino acid substitution is an L70R substitution. In another embodiment, the variant comprises one of the amino acid substitutions selected from the group consisting of G127R/F511Y, L70Q/G94A/R262G/F305L, F12S/T15A/E18G/N297K, S396T/T442I, V10M/E323K, F120L/A266G, K438N/K500R, V79L/S509N, E175V/S257A/E368D/A469S, T71S/L36374, F280S/H440S, E89S/H440, V58S/A328S/N532S, S119S/D S/I449S and K S/G507.

In another aspect, the invention provides a polypeptide comprising SEQ ID NO: 120 (figure 19).

In another aspect, the present invention provides a method of producing isoprene, comprising: (a) providing a host cell comprising an expression vector comprising a polynucleotide sequence encoding an isoprene synthase variant; and (b) culturing the host cell under conditions suitable for the production of isoprene. In one embodiment, the method further comprises (c) recovering the isoprene. In another embodiment, the method further comprises (d) polymerizing the isoprene.

In another aspect, the present invention provides a method for detecting isoprene synthase activity, comprising: (a) culturing a host cell comprising an expression vector under conditions suitable for production of the isoprene synthase variant; (b) lysing the host cells with a lysis buffer comprising lysozyme to produce a cell lysate; and (c) detecting isoprene synthase activity in the cell lysate by measuring isoprene production from dimethylallyl Diphosphate (DMAPP). In one embodiment, the host cell is selected from the group consisting of a gram-positive bacterial cell, a gram-negative bacterial cell, a filamentous fungal cell, and a yeast cell. In another embodiment, the host cell is selected from the group consisting of an Escherichia species (E.coli), a Pantoea species (Pantoea citrea), a Bacillus species (Bacillus subtilis), a yarrowia species (yarrowia lipolytica), and a Trichoderma (Trichoderma reesei). In another embodiment, the host cell is cultured in a medium comprising a carbon source selected from the group consisting of glucose, glycerol, dihydroxyacetone, yeast extract, biomass, molasses, sucrose and oil.

In another aspect, the invention provides a host cell comprising a heterologous polynucleotide sequence encoding an isoprene synthase variant operably linked to a promoter, wherein the isoprene synthase variant comprises a substitution at a position corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues of poplar isoprene synthase. In one embodiment, the isoprene synthase is SEQ ID NO: poplar isoprene synthase of 120. In another embodiment, the variant is selected from the group consisting of MEA variant (SEQ ID NO: 122), MSV variant (SEQ ID NO: 124), MVS variant (SEQ ID NO: 126), MTE variant (SEQ ID NO: 128), MNV variant (SEQ ID NO: 130). In another embodiment, the variant is selected from the group consisting of a TRC (-3) variant (SEQ ID NO: 136), a TRC (-4) variant (SEQ ID NO: 138), a TRC (-5) variant (SEQ ID NO: 140), a TRC (-6) variant (SEQ ID NO: 142), and a TRC (-7) variant (SEQ ID NO: 144). In another embodiment, the variant is a MET variant of Populus tremuloides isoprene synthase (SEQ ID NO: 146). In another embodiment, the variant is a MET variant of lasiocarpus lanuginosus isoprene synthase (SEQ ID NO: 148). In another embodiment, the variant comprises one of the amino acid substitutions selected from the group consisting of V10M, F12S, T15A, E18G, V58I, V58F, L70Q, L70V, T71V, V79V, E89V, G94V, S119V, F120V, G127V, E175V, T212V, S257V, R262V, a 266V, F280V, N297V, F305V, L319V, E323V, a 328V, D342V, a 359V, K366V, E368V, L374V, S396V, V418V, K438V, H440V, T36442, I V, a 36449V, K4672, K V, N507V, N507V, N. In another embodiment, the at least one amino acid substitution is an L70R substitution. In another embodiment, the variant comprises one of the amino acid substitutions selected from the group consisting of G127R/F511Y, L70Q/G94A/R262G/F305L, F12S/T15A/E18G/N297K, S396T/T442I, V10M/E323K, F120L/A266G, K438N/K500R, V79L/S509N, E175V/S257A/E368D/A469S, T71S/L36374, F280S/H440S, E89S/H440, V58S/A328S/N532S, S119S/D S/I449S and K S/G507. In another embodiment, the polynucleotide sequence is contained within a plasmid. In another embodiment, the polynucleotide sequence is integrated into the chromosome of the host cell. In another embodiment, the host is selected from the group consisting of gram-positive bacterial cells, gram-negative bacterial cells, filamentous fungal cells and yeast cells. In another embodiment, the host is selected from the group consisting of an Escherichia species (E.coli), a Pantoea species (Pantoea citrea), a Bacillus species (Bacillus subtilis), a yarrowia species (yarrowia lipolytica), and a Trichoderma (Trichoderma reesei). In another embodiment, the host cell is cultured in a medium comprising a carbon source selected from the group consisting of glucose, glycerol, dihydroxyacetone, yeast extract, biomass, molasses, sucrose and oil. In another embodiment, the host cell further comprises a heterologous or native nucleic acid encoding an IDI polypeptide and/or a heterologous or native nucleic acid encoding a DXS polypeptide, optionally in combination with a native DXP pathway. In another embodiment, the host cell further comprises one or more nucleic acids encoding an IDI polypeptide and a DXS polypeptide. In another embodiment, the host cell comprises a vector encoding the isoprene synthase variant, the IDI polypeptide, and the DXS polypeptide. In another embodiment, the host cell further comprises a heterologous nucleic acid encoding a MVA pathway polypeptide selected from the group consisting of MVA pathway polypeptides from Saccharomyces cerevisiae (Saccharomyces cerevisiae) and Enterococcus faecalis (Enterococcus faecalis). In another embodiment, the host cell further comprises one or more nucleic acids encoding a MVA pathway polypeptide and a DXS polypeptide, and wherein one vector encodes the isoprene synthase variant, the MVA pathway polypeptide, and the DXS polypeptide. In another embodiment, the host cell further comprises one or more nucleic acids encoding a DXS polypeptide, an IDI polypeptide, or one or more of the remaining DXP pathway polypeptides and an MVA pathway polypeptide.

In another aspect, the present invention provides a method of producing isoprene, comprising: (a) culturing a host cell comprising a heterologous polynucleotide sequence encoding an isoprene synthase variant operably linked to a promoter under suitable culture conditions for the production of isoprene, wherein the isoprene synthase variant comprises a substitution at a position corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues of poplar isoprene synthase; and (b) producing isoprene. In one embodiment, the method further comprises (c) recovering the isoprene. In another embodiment, the method further comprises (d) polymerizing the isoprene.

In another aspect, the present invention provides a method of producing isoprene synthase, comprising: (a) providing: (i) a host cell; and (ii) a nucleic acid encoding an isoprene synthase variant operably linked to a promoter, wherein the isoprene synthase variant is mutated in a region that is complementary to a region of SEQ ID NO: 120 at positions corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues; (b) contacting a host cell with the nucleic acid to produce a transformed host cell; and (c) culturing the transformed host cell under suitable culture conditions for the production of isoprene synthase.

Brief Description of Drawings

FIG. 1 provides the coding sequence of a codon-optimized kudzu (Pueraria montana) isoprene synthase for expression in E.coli (SEQ ID NO: 1).

FIG. 2 provides the amino acid sequence of kudzu isoprene synthase (SEQ ID NO: 2).

FIG. 3 provides the coding sequence (SEQ ID NO: 6) for codon-optimized poplar (Populus alba x tremula) isoprene synthase for expression in E.coli.

FIG. 4 provides the amino acid sequence of poplar (Populus alba x Populus tremula) isoprene synthase (SEQ ID NO: 7).

Figure 5 provides a homology model for pueraria isoprene synthase with cysteine residues highlighted as space-filling molecules.

FIG. 6 provides a homology model for poplar isoprene synthase, with cysteine residues highlighted as space filling molecules (dark grey). In addition, the cysteine residues from the kudzu model of fig. 5 were superimposed as space filling molecules (light grey) onto the poplar model.

Figure 7 provides a graph showing the growth curve of the ge IspS cysteine mutant of example 5.

FIG. 8 shows the results of SDS-PAGE analysis of the Pueraria IspS cysteine mutants from lysed cells. The pellet and supernatant fractions were prepared by centrifugation.

FIG. 9 provides a map of plasmid MCM93 (pCR2.1-Kudzu).

FIG. 10 provides the nucleotide sequence of plasmid MCM93 (SEQ ID NO: 22).

FIG. 11 provides a map of pET 24D-Kudzu.

FIG. 12 provides the nucleotide sequence of pET24D-Kudzu (SEQ ID NO: 23).

FIG. 13 shows the result of SDS-PAGE analysis of inclusion bodies containing pueraria isoprene synthase. Lane M contains molecular weight markers, while the remaining lanes contain incremental amounts of purified inclusion body preparations. The pueraria isoprene synthase was estimated to have a purity of > 90%.

FIG. 14 provides a graph showing isoprene synthase activity of kudzu Site Evaluation Library (SEL) members for Y22, A20, and S408 positions. Most members showed highly reduced activity, while conservative substitutions showed less reduction in activity. Panel A shows the results of the validation of Y22 library members compared to an independent wild type sample (circled WT). Panel B shows the results of the validation of the A20 library members compared to the wild type sample (circled WT). Panel C shows the results of the validation of the S408 library members, indicating that member S408D has 1.5 to 2-fold greater activity than the average of the wild-type controls.

FIG. 15 shows MVA and DXP metabolic pathways for isoprene (based on F. Bouvier et al, Progress in Lipid Res.44: 357-429, 2005). The following description includes alternative names for each polypeptide in the pathway and references disclosing assays for measuring the activity of the polypeptides (each of these references is thus incorporated by reference in its entirety, in particular assays for determining the activity of polypeptides in the MVA and DXP pathways, respectively). Mevalonate pathway: AACT; acetyl-CoA acetyltransferase, MvaE, EC 2.3.1.9, assay: bacteriol, 184: 2116-2122, 2002; HMGS; hydroxymethylglutaryl-CoA synthase, MvaS, EC 2.3.3.10, assay: bacteriol, 184: 4065-; HMGR; 3-hydroxy-3-methylglutaryl-CoA reductase, MvaE, EC 1.1.1.34, assay: bacteriol, 184: 2116-2122, 2002; MVK; mevalonate kinase, ERG12, EC 2.7.1.36, assay: curr Genet 19: 9-14, 1991; PMK; phosphomevalonate kinase, ERG8, EC 2.7.4.2, assay: mol Cell biol., 11: 620, 631, 1991; DPMDC; mevalonate diphosphate decarboxylase, MVD1, EC 4.1.1.33, assay: biochemistry, 33: 13355, 13362, 1994; IDI; isopentenyl diphosphate delta-isomerase, IDI1, EC 5.3.3.2, assay: j.biol.chem.264: 19169-19175, 1989. DXP pathway: DXS; 1-deoxyxylulose-5-phosphate synthase, dxs, EC 2.2.1.7, assay: PNAS, 94: 12857-62, 1997; DXR; 1-deoxy-D-xylulose 5-phosphate reductoisomerase, dxr, EC 2.2.1.7, assay: eur.j.biochem.269: 4446-4457, 2002; MCT; cytidine-2C-methyl-D-erythritol 4-diphosphate synthase, IspD, EC 2.7.7.60, assay: PNAS, 97: 6451 6456, 2000; CMK; cytidine-2-C-methyl-D-erythritol 4-diphosphate kinase, IspE, EC 2.7.1.148, assay: PNAS, 97: 1062-1067, 2000; MCS; 2C-methyl-D-erythritol 2, 4-cyclodiphosphate synthase, IspF, EC 4.6.1.12, assay: PNAS, 96: 11758-11763, 1999; HDS; 1-hydroxy-2-methyl-2- (E) -butenyl 4-diphosphate synthase, ispG, EC 1.17.4.3, assay: j.org.chem., 70: 9168-9174, 2005; HDR; 1-hydroxy-2-methyl-2- (E) -butenyl 4-bisphosphate reductase, IspH, EC 1.17.1.2, assay: JACS, 126: 12847-12855, 2004.

FIG. 16 provides a diagram of pDu 27.

FIG. 17 provides the amino acid sequence of pDu 27A 6 × his labeled Populus alba IspS amino acid sequence (SEQ ID NO: 118).

FIG. 18 provides the nucleotide sequence of plasmid pDu27 (SEQ ID NO: 119).

FIG. 19 provides the amino acid sequence of full length Populus alba IspS in pET24a (SEQ ID NO: 120). The underlined residues indicate the positions of the amino-terminal truncations within the IspS in plasmids pDu39 to pDu 43.

FIG. 20 provides the nucleotide sequence of Populus alba plasmid pDu27 (SEQ ID NO: 121).

FIG. 21 shows that purified IspS shows a lower molecular weight "doublet" by SDS-PAGE analysis.

Figure 22 shows tryptic peptides identified by mass spectrometry.

FIG. 23 provides a map of the amino-terminal truncations pDu40, pDu41, pDu42 and pDu43 carrying Populus alba IspS.

FIG. 24 provides a map of Pdu39 (in strain MD 09-173) as untagged pET24 a-Populus alba MEA

FIG. 25 provides the amino acid sequence of a truncated "MEA" variant of the Populus alba IspS at pDu39 (SEQ ID NO: 122).

FIG. 26 provides the nucleotide sequence of plasmid pDu39 (SEQ ID NO: 123).

FIG. 27 provides the amino acid sequence of a truncated "MSV" variant of Populus alba IspS at pDu41 (SEQ ID NO: 124).

FIG. 28 provides the nucleotide sequence (SEQ ID NO: 125) of plasmid pDu41 (untagged pET24 a-Populus alba (MSV)).

FIG. 29 provides the amino acid sequence of a truncated "MVS" variant of the Populus alba IspS in pDu43 (SEQ ID NO: 126).

FIG. 30 provides the nucleotide sequence (SEQ ID NO: 127) of plasmid pDu43 (untagged pET24 a-Populus alba (MVS)).

FIG. 31 provides the amino acid sequence of a truncated "MTE" variant of the Populus alba IspS at pDu42 (SEQ ID NO: 128).

FIG. 32 provides the nucleotide sequence (SEQ ID NO: 129) of plasmid pDu42 (untagged pET24 a-Populus alba (MTE)).

FIG. 33 provides the amino acid sequence of a truncated "MNV" (SEQ ID NO: 130) of the Populus alba IspS in pDu 40.

FIG. 34 provides the nucleotide sequence (SEQ ID NO: 131) of plasmid pDu40 (untagged pET24 a-Populus alba (MNV)).

FIG. 35 provides a graph of carboxy-terminal plus TEV, 6 XHis-tagged IspS variants MD09-161 and MD 09-163.

FIG. 36 provides the amino acid sequence of Populus alba MEA (+) TEV in MD09-163 (SEQ ID NO: 132).

FIG. 37 provides the nucleotide sequence (SEQ ID NO: 133) of plasmid MD09-163(pET24a-MEA (+) TEV). CDS is underlined and TEV protease sites are in bold.

FIG. 38 provides the amino acid sequence of Populus alba FL (+) TEV in MD09-161 (SEQ ID NO: 134).

FIG. 39 provides the nucleotide sequence (SEQ ID NO: 135) of plasmid MD09-161(pET24a-FL (+) TEV). CDS is underlined and TEV protease sites are in bold.

FIG. 40 shows graphs representing the specific activities of MD09-167, Full Length (FL), MD09-165, and truncated isoprene synthase (MD 09-173). The reaction is carried out at 30 DEG CFor 15 minutes in a solution containing 100mM Tris, 100mM NaCl, 50mM MgCl₂5mM DMAPP and 2.5-4.5. mu.g of isoprene synthase in the supernatant of the whole cell lysate.

FIG. 41 shows a graph demonstrating the rate/[ E ] versus [ DMAPP ]. X represents MD09-173, circles represent MD09-167, diamonds represent MD09-165 and squares represent full-length IspS.

FIG. 42 shows a graph showing isoprene synthase activity versus [ DMAPP ]. X's represent data generated with the MD09-173 truncated isoprene synthase. Circles represent data generated with MD09-167 isoprene synthase. Diamonds represent data generated with MD09-165 isoprene synthase. The squares represent data generated with full length isoprene synthase. Each data set was from an independently grown culture in triplicate.

FIG. 43 shows the different k_catAnd K_MAnd K_iGraph of the effect on reaction rate. In panel A, curve 1 represents the rate equation for truncated isoprene synthase activity divided by the full-length isoprene synthase rate equation plotted at different DMAPP concentrations. Curve 2 represents the rate equation for full-length isoprene synthase (where k is _catHas been truncated for isoprene synthase k_catSubstitution) divided by the full-length isoprene synthase rate equation. Curve 3 represents the rate equation for full-length isoprene synthase (where K_MHas been truncated for isoprene synthase K_MSubstitution) divided by the full-length isoprene synthase rate equation. Curve 4 represents the rate equation for full-length isoprene synthase (where K_iHas been truncated for isoprene synthase K_iSubstitution) divided by the full-length isoprene synthase rate equation. Panel B shows a graph showing the rate equation for truncated isoprene synthase versus the ratio of full-length isoprene synthase versus [ DMAPP]Fitting the data of (1).

Fig. 44 shows a graph showing the growth inhibition of MCM531 by Mevalonate (MVA). Cells were incubated in microtiter plates in TM3 medium with different concentrations of MVA. At the placeShown time measurements OD of quadruplicate wells₆₀₀。

Fig. 45 shows a graph of a DMAPP assay displaying L70SSL plates. The dark bars represent full-length (aspen pET24a) or pDU39 (truncated) controls. Variants in the C3(27), D3(39) or E3(51) wells were selected for further analysis.

Figure 46 shows a graph showing the average specific activity of all variants selected for DMAPP assay with protein assay. Error bars represent one standard deviation. All 3L 70R variants showed higher activity than the control (WT).

Figure 47 shows a graph showing the average specific activity of all 3L 70R variants compared to the "MEA" truncated populus alba IspS enzyme. Error bars represent one standard deviation.

FIG. 48 provides a map of plasmids pDu47-3, pDu47-4, and pDu 47-5.

FIG. 49 provides a map of plasmids pDu47-6, pDu47-7, and pDu 48.

FIG. 50 provides a map of plasmids pDu49, pDu50, and pDu 50-4.

FIG. 51 provides the amino acid sequence of Populus alba TRC (-3) in pDu47-3 (SEQ ID NO: 136).

FIG. 52 provides the nucleotide sequence of plasmid pDu47-3 (SEQ ID NO: 137).

FIG. 53 provides the amino acid sequence (SEQ ID NO: 138) of Populus alba TRC (-4) in pDu 47-4.

FIG. 54 provides the nucleotide sequence of plasmid pDu47-4 (SEQ ID NO: 139).

FIG. 55 provides the amino acid sequence of Populus alba TRC (-5) in pDu47-5 (SEQ ID NO: 140).

FIG. 56 provides the nucleotide sequence of plasmid pDu47-5 (SEQ ID NO: 141).

FIG. 57 provides the amino acid sequence (SEQ ID NO: 142) of Populus alba TRC (-6) in pDu 47-6.

FIG. 58 provides the nucleotide sequence of plasmid pDu47-6 (SEQ ID NO: 143).

FIG. 59 provides the amino acid sequence of Populus alba TRC (-7) in pDu47-7 (SEQ ID NO: 144).

FIG. 60 provides the nucleotide sequence of plasmid pDu47-7 (SEQ ID NO: 145).

FIG. 61 provides the amino acid sequence (SEQ ID NO: 146) of pDu48 Populus tremula TRC (MET).

FIG. 62 provides the nucleotide sequence of plasmid pDu48 (SEQ ID NO: 147).

FIG. 63 provides the amino acid sequence (SEQ ID NO: 148) of Populus Tomentosa (TRC) in pDu 49.

FIG. 64 provides the nucleotide sequence of plasmid pDu49 (SEQ ID NO: 149).

FIG. 65 provides the amino acid sequence of kudzu TRC (MEA) at pDu50 (SEQ ID NO: 150).

FIG. 66 provides the nucleotide sequence of plasmid pDu50 (SEQ ID NO: 151).

FIG. 67 provides the amino acid sequence of Kudzuvine TRC (-4) in pDu50-4 (SEQ ID NO: 152).

FIG. 68 provides the nucleotide sequence of plasmid pDu50-4 (SEQ ID NO: 153).

Figure 69 shows a graph showing raw data and OD normalization data from DMAPP assays for truncated variants of IspS.

FIG. 70 shows a graph representing the specific activity of the truncated IspS. The specific activities of the cottonwood, populus tremuloides and populus tomentosa truncations were compared relative to the "full-length" variation of the cottonwood.

FIG. 71 provides a map of plasmid p 9795.

FIG. 72 provides the nucleotide sequence of plasmid p9795 (SEQ ID NO: 154).

FIG. 73 provides a map of plasmid pTrcKudzu.

FIG. 74 provides the nucleotide sequence of plasmid pTrcKudzu (SEQ ID NO: 155).

FIG. 75 provides a map of plasmid pMAL-C4X.

FIG. 76 provides the nucleotide sequence of plasmid pMAL-C4X (SEQ ID NO: 156).

FIG. 77 provides a map of plasmid pMAL-C4X-Kudzu.

FIG. 78 provides the nucleotide sequence of plasmid pMAL-C4X-Kudzu (SEQ ID NO: 157).

FIG. 79 provides a map of the plasmids pET24, Populus deltoides pET24a, and Populus tomentosa pET24 a.

FIG. 80 provides the amino acid sequence of Populus tremula IspS in Populus tremula pET24a (SEQ ID NO: 158).

FIG. 81 provides the nucleotide sequence (SEQ ID NO: 159) of plasmid Populus tremula pET24 a.

FIG. 82 provides the amino acid sequence of Populus deltoides IspS in Populus deltoides pET24a (SEQ ID NO: 160).

FIG. 83 provides the nucleotide sequence of plasmid hairy fruit poplar pET24a (SEQ ID NO: 161).

Figure 84 provides a map of plasmids pDu30, pDu31, and pDu 32.

FIG. 85 provides the amino acid sequence of the IspS variant Populus alba TRC-pET200 in pDu30 (SEQ ID NO: 162).

FIG. 86 provides the nucleotide sequence of pDu30 (SEQ ID NO: 163).

FIG. 87 provides the amino acid sequence (SEQ ID NO: 164) of the IspS variant Populus tremuloides TRC-pET200 in pDu 31.

FIG. 88 provides the nucleotide sequence of pDu31 (SEQ ID NO: 165).

FIG. 89 provides the amino acid sequence (SEQ ID NO: 166) of the IspS variant Populus tomentosa TRC-pET200 in pDu 32.

FIG. 90 provides the nucleotide sequence of pDu32 (SEQ ID NO: 167).

Figure 91 provides the three-dimensional structure of populus deltoids IspS shown as dimers. Chain a is dark gray, chain B is medium gray and the individual magnesium ions in each active center are light gray.

Figure 92 provides a monomer view of the populus tremuloides IspS structure. Magnesium is shown as a light gray sphere and the amino and carboxyl termini are indicated.

FIG. 93 shows structural alignments between (A) BdpS and LS, (B) BdpS and Populus IspS, (C) LS and Populus IspS, and (D) TEAS and Populus IspS. In each case, the first structure is light gray and the second structure is dark gray. The divalent magnesium ions are shown as spheres.

FIG. 94 shows the three-dimensional structure of the loops in Bdp S and LS. Panel A shows the amino terminal ring of Ls in light grey and the amino terminal ring of BdpS in dark grey. Panel B shows that Ring I and Ring II are structurally homologous.

Figure 95 shows that the amino terminal loops of BdpS (dark grey) and poplar IspS (light grey) are structurally divergent. Panel A shows the amino terminal ring and panel B shows ring I and ring II.

Figure 96 shows LS (light grey) and poplar IspS (dark grey) amino terminal rings are structurally divergent. Panel A shows the amino terminal ring and panel B shows ring I and ring II.

Figure 97 shows that the amino terminal loops of TEAS (light grey) and poplar IspS (dark grey) are structurally divergent. Panel A shows the amino terminal ring and panel B shows ring I and ring II. Loop I twists in the TEAS.

General description of the invention

The practice of the present invention involves, unless otherwise indicated, conventional techniques commonly used in molecular biology, microbiology, and recombinant DNA, which are within the capabilities of those skilled in the art. Such techniques are known to those skilled in the art and are described in numerous texts and references (see, e.g., Sambrook et al, "Molecular Cloning: A Laboratory Manual," 2 nd edition, Cold Spring Harbor, 1989; and Ausubel et al, "Current Protocols in Molecular Biology," 1987).

Unless otherwise defined herein, all terms and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. For example, Singleton et al, DICTIONARY OF MICROBIOLOGY AND MOLECULAR BIOLOGY, 2 nd ed., John Wiley AND Sons, New York (1994); and Hale and Markham, THE HARPER COLLINS DICTIONARY OF BIOLOGY, Harper Perennial, NY (1991) provide those skilled in the art with a general DICTIONARY OF the many terms used in this invention. Although any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred methods and materials are described herein. Accordingly, the terms defined immediately below are more fully described by reference to this specification in their entirety.

Further, the headings provided herein are not limitations of the various aspects or embodiments of the invention which can be had by reference to the specification as a whole. Accordingly, the terms defined immediately below are described more fully by reference to this specification in their entirety. However, to facilitate an understanding of the present invention, numerous terms are defined below.

Definition of

Unless defined otherwise herein, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred methods and materials are described herein. Accordingly, the terms defined immediately below are more fully described by reference to this specification in their entirety.

As used herein, the singular forms "a", "an" and "the" include plural references unless the context clearly dictates otherwise. Unless otherwise indicated, nucleic acids are written in a 5 'to 3' direction; amino acid sequences are written in the amino to carboxyl direction. It is to be understood that this invention is not limited to the particular methodology, protocols, and reagents described, as these may vary depending on the context in which they are used by those skilled in the art.

It is intended that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

All documents mentioned in this specification are incorporated in relevant part by reference. However, the citation of any document is not to be construed as an admission that it is prior art with respect to the present invention.

As used herein, the term 2-methyl-1, 3-butadiene (CAS # 78-79-5) ("isoprene") refers to the direct and final volatile C5 hydrocarbon product resulting from the elimination of pyrophosphate from 3, 3-dimethylallyl pyrophosphate (DMAPP) and does not involve linking or polymerizing [ one ] IPP molecule to [ one ] DMAPP molecule. As used herein, the terms "isoprene synthase" and "IspS" refer to enzymes that catalyze the elimination of pyrophosphate from dimethylallyl Diphosphate (DMAPP) to form isoprene. In some preferred embodiments, the IspS is an enzyme obtained from a plant such as pueraria lobata, poplar, or quercus rubra. In some embodiments, the term "IspS" refers to a naturally occurring mature enzyme or portion thereof.

Related (and derivative) proteins include "variant proteins". In some preferred embodiments, variant proteins differ from the parent protein (e.g., Pueraria IspS or Populus IspS described as SEQ ID NO: 2) and from each other by a small number of amino acid residues. The number of different amino acid residues may be one or more, preferably 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50 or more amino acid residues. In some preferred embodiments, the number of different amino acids between variants is between 1 and 10. In some particularly preferred embodiments, the related proteins, and particularly variant proteins, comprise at least 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, or 99% amino acid sequence identity. Additionally, a related protein or variant protein as used herein refers to a protein that differs from another related protein or parent protein in the number of prominent regions. For example, in some embodiments, the variant protein has 1, 2, 3, 4, 5, or 10 corresponding prominent regions that differ from the parent protein.

Several methods suitable for producing variants of the enzymes of the invention are known in the art, including, but not limited to, site-saturation mutagenesis, scanning mutagenesis, insertional mutagenesis, random mutagenesis, site-directed mutagenesis, and directed evolution, as well as a variety of other recombinant methods.

Characterization of the wild type and mutant proteins is achieved by any means or suitable "assay" and is preferably based on an assessment of the property of interest. For example, in some embodiments of the invention, one or more of the following characteristics are evaluated: pH stability; temperature stability; oxidation stability; stability of proteolysis; solubility; km and/or specific activity for the conversion of DMAPP to isoprene in vitro; km and/or specific activity of DMAPP converted to isoprene in vivo in the environment of a host organism (e.g., e.coli); and expression of DXP pathway and/or MVA pathway enzymes. Indeed, it is contemplated that enzymes having various degrees of stability, solubility, activity and/or expression levels under one or more assay conditions will be useful in the present invention.

As used herein, the term "gene" refers to a polynucleotide (e.g., a DNA segment) that encodes a polypeptide and includes regions preceding and following the coding region, as well as intervening sequences (introns) between individual coding segments (exons).

As used herein, "homologous genes" refers to a pair of genes from different but usually related species that correspond to each other and are identical or very similar to each other. The term includes genes that are sequestered by speciation (i.e., development of a new species) (e.g., orthologous genes) as well as genes that are sequestered by genetic duplication (e.g., paralogous genes).

As used herein, "ortholog" and "orthologous gene" refer to genes in different species that have evolved from a common ancestral gene (i.e., a homologous gene) due to speciation. In general, orthologs retain the same function during evolution. The identification of orthologs is used to reliably predict gene function in newly sequenced genomes.

As used herein, "paralogs" and "paralogous genes" refer to genes that are related due to internal duplication of the genome. Although orthologs retain the same function throughout evolution, paralogs evolve new functions, although some are often related to the original function.

As used herein, "homology" refers to sequence similarity or identity, preferably identity. This homology is determined using standard techniques known in the art (see, e.g., Smith and Waterman, adv. adv Appl Math, 2: 482, 1981; Needleman and Wunsch, J Mol Biol, 48: 443, 1970; Pearson and Lipman, Proc Natl Acad Sci USA, 85: 2444, 1988; programs such as Wisconsin Genetics Software Package (Wisconsin Genetics Software Package) Genetics Computer Group, Madison, GAP, BESTFIT, FASTA and TFASTA in WI and Devereux et al, Nucl Acid Res, 12: 387-395, 1984).

As used herein, an "analogous sequence" is a sequence in which the function of the gene is substantially identical to that of a gene based on pueraria isoprene synthase (IspS) or poplar IspS (IspS). Additionally, similar genes include at least 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99% or 100% sequence identity to the sequence of pueraria isoprene synthase. In additional embodiments, more than one of the above characteristics applies to the sequence. Similar sequences are determined by known methods of sequence alignment. The alignment method commonly used is BLAST, although as indicated above and below, there are other methods that are also used to align sequences.

An example of a useful algorithm is PILEUP. Using progressive pairwise alignment, PILEUP generates multiple sequence alignments from a set of related sequences. It can also plot a tree that shows the clustering relationships used to generate the alignment results. PILEUP uses a simplified version of the Feng and Doolittle progressive alignment method (Feng and Doolittle, J Mol Evol, 35: 351-360, 1987). The method is similar to that described by Higgins and Sharp (Higgins and Sharp, CABIOS 5: 151-153, 1989). Useful PILEUP parameters include a default gap weight of 3.00, a default gap length weight of 0.10, and weighted end gaps.

Another example of a useful algorithm is the BLAST algorithm described by Altschul et al (Altschul et al, J Mol Biol, 215: 403-410, 1990 and Karlin et al, Proc Natl Acad Sci USA, 90: 5873-5787, 1993). A particularly useful BLAST program is the WU-BLAST-2 program (see Altschul et al, Meth Enzymol, 266: 460-480, 1996). WU-BLAST-2 uses several search parameters, most of which are set to default values. Adjustable parameters are set with the following values: the overlap coverage area is 1, the overlap score is 0.125, and the word threshold (T) is 11. The HSP S and HSP S2 parameters are dynamic values and are established by the program itself based on the composition of the particular sequence and the composition of the particular database against which the sequence of interest is retrieved. However, the value may be adjusted to improve sensitivity. The% amino acid sequence identity value is determined by dividing the number of matching identity residues by the total number of residues of the "longer" sequence in the aligned region. The "longer" sequence is the sequence with the most actual residues in the aligned region (gaps introduced by WU-Blast-2 to maximize alignment score are ignored).

Thus, "percent (%) nucleic acid sequence identity" is defined as the percentage of nucleotide residues in a candidate sequence that are identical to the nucleotide residues in the starting sequence (i.e., the sequence of interest). The preferred method uses the BLASTN module of WU-BLAST-2 set to default parameters with overlap coverage and overlap score set to 1 and 0.125, respectively.

As used herein, the term "hybridization" refers to the process by which one strand of a nucleic acid binds to a complementary strand through base pairing as is known in the art.

A nucleic acid sequence and a reference nucleic acid sequence are considered to "selectively hybridize" if the two specifically hybridize to each other under high stringency hybridization and wash conditions. Hybridization conditions are based on the melting temperature (Tm) of the nucleic acid binding complex or probe. For example, "maximum stringency" typically occurs at about Tm-5 ℃ (5 ℃ below the Tm of the probe; "high stringency" occurs at about 5-10 ℃ below the Tm; "moderate stringency" occurs at about 10-20 ℃ below the Tm of the probe and "low stringency" occurs at about 20-25 ℃ below the Tm. Functionally, conditions of maximum stringency can be used to identify sequences that are strictly or nearly strictly identical to the hybridization probes; while medium or low stringency hybridization can be used to identify or detect polynucleotide sequence homologs.

Moderate and high stringency hybridization conditions are well known in the art. Examples of high stringency conditions include hybridization at about 42 ℃ in 50% formamide, 5 XSSC, 5 XDenhardt's solution, 0.5% SDS and 100. mu.g/ml denatured carrier DNA followed by 2 washes in 2 XSSC and 0.5% SDS at room temperature and 2 additional washes in 0.1 XSSC and 0.5% SDS at 42 ℃. Examples of moderately stringent conditions include incubation overnight at 37 ℃ in a solution comprising 20% formamide, 5 XSSC (150mM NaCl, 15mM trisodium citrate), 50mM sodium phosphate (pH 7.6), 5 XDenhardt's solution, 10% dextran sulfate, and 20mg/ml denatured sheared salmon sperm DNA, followed by washing of the filters in 1 XSSC at about 37-50 ℃. One skilled in the art would know how to adjust the temperature, ionic strength, etc. as needed to accommodate factors such as probe length.

As used herein, "recombinant" includes reference to a cell or vector, wherein the cell or vector has been modified by the introduction of a heterologous nucleic acid sequence or the cell is derived from a cell so modified. Thus, for example, a recombinant cell expresses a gene that is not present in the same form in the native (non-recombinant) form of the cell or expresses a native gene that is otherwise abnormally expressed, under-expressed, or not expressed at all by deliberate human intervention. "recombination," and the production of "recombinant" nucleic acids is generally the assembly of two or more nucleic acid fragments, wherein the assembly produces a chimeric gene.

In a preferred embodiment, the mutant DNA sequence is generated by site-saturation mutagenesis in at least one codon. In another preferred embodiment, 2 or more codons are subjected to site-saturation mutagenesis. In yet another embodiment, the mutant DNA sequence has greater than 50%, greater than 55%, greater than 60%, greater than 65%, greater than 70%, greater than 75%, greater than 80%, greater than 85%, greater than 90%, greater than 95%, or greater than 98% homology to the wild-type sequence. In alternative embodiments, the mutant DNA is generated in vivo using any known mutagenesis method, such as, for example, radiation, nitrosoguanidine, and the like. The desired DNA sequence is subsequently isolated and used in the methods provided herein.

As used herein, the term "target sequence" refers to a DNA sequence in a host cell that encodes a sequence in which it is desired to insert the entry sequence into the host cell genome. In some embodiments, the target sequence encodes a functional wild-type gene or operon, while in other embodiments, the target sequence encodes a functional mutant gene or operon, or a non-functional gene or operon.

As used herein, "flanking sequence" refers to any sequence located upstream or downstream of the sequence in question (e.g., for genes A-B-C, gene B is flanked by the A and C gene sequences). In a preferred embodiment, the entry sequence has a homology cassette on each side. In another embodiment, the entry sequence and homology cassette comprise units with stuffer sequences on each side. In some embodiments, the flanking sequence is present on only a single side (either the 3 'or 5' side), but in preferred embodiments it is present on each side of the sequence that is flanked by the flanking sequences. In some embodiments, the flanking sequence is present on only a single side (either the 3 'or 5' side), while in preferred embodiments it is present on each side of the sequence that is flanked.

As used herein, the term "stuffer sequence" refers to any additional DNA (typically vector sequences) that flank the homology box. However, the term includes any non-homologous DNA sequence. Without being bound by any theory, the fill sequence provides an unimportant target for the cell to initiate DNA uptake.

As used herein, the terms "amplification" and "gene amplification" refer to a process by which a particular DNA sequence is disproportionately replicated so that the amplified gene is present at a higher copy number than originally present in the genome. In some embodiments, cells are selected for growth in the presence of a drug (e.g., an inhibitor of a cocoa inhibitory enzyme), which results in amplification of an endogenous gene encoding a gene product required for growth in the presence of the drug, or by amplification of an exogenous (i.e., import) sequence encoding such a gene product, or both.

"amplification" is a particular situation involving template-specific nucleic acid replication. It should be contrasted with non-specific template replication (i.e., replication that has template dependency but is not dependent on a specific template). Template specificity is distinguished here from replication fidelity (i.e.the synthesis of the correct polynucleotide sequence) and nucleotide (ribose or deoxyribose) specificity. Template specificity is often described in terms of "target" specificity. Target sequences are "targets" in the sense that they are intended to be sorted out from other nucleic acids. Amplification techniques have been designed primarily for this sorting process.

As used herein, the term "co-amplifying" refers to introducing an amplifiable marker into a single cell along with other gene sequences (i.e., comprising one or more non-selectable genes, such as those contained within an expression vector) and applying appropriate selection pressure so that the cell amplifies the amplifiable marker and the remaining non-selectable gene sequences. The amplifiable marker may be physically linked to the remaining gene sequence, or alternatively, two separate DNA fragments (one fragment containing the amplifiable marker and the other containing the non-selectable marker) may be introduced into the same cell.

As used herein, the terms "amplifiable marker", "amplifiable gene" and "amplification vector" refer to a gene or a vector encoding a gene that allows amplification of the gene under suitable growth conditions.

"template specificity" is achieved in most amplification techniques by selection of enzymes. Amplification enzymes are enzymes that, under the conditions in which they are used, only process a particular nucleic acid sequence in a heterogeneous mixture of nucleic acids. In the case of Q.beta.replicase, for example, MDV-I RNA is the specific template for the replicase (see, e.g., Kacian et al, Proc Natl Acad Sci USA 69: 3038, 1972) and other nucleic acids are not replicated by this amplicase. Similarly, in the case of T7RNA polymerase, this amplification enzyme has strict specificity for its own promoter (see Chamberlin et al, Nature 228: 227 (1970)). In the case of T4DNA ligase, the enzyme does not ligate two oligonucleotides or polynucleotides where there is a mismatch between the oligonucleotide or polynucleotide substrate and the template at the ligation junction (see Wu and Wallace, Genomics 4: 560, 1989). Finally, due to the ability of Taq and Pfu polymerase to function at high temperatures, it was found that these two enzymes exhibit a high degree of specificity for the sequences to which they are bound by the primers and thus defined; the high temperature creates thermodynamic conditions that favor the hybridization of the primer to the target sequence and not to non-target sequences.

As used herein, the term "amplifiable nucleic acid" refers to a nucleic acid that can be amplified by any amplification method. It is contemplated that "amplifiable nucleic acids" will typically comprise "sample templates".

As used herein, the term "sample template" refers to nucleic acids derived from a sample that is analyzed for the presence of a "target" (defined below). In contrast, "background template" is used to refer to nucleic acids that are not templates for a sample, which may or may not be present in the sample. Background templates are most often present by chance. It may be the result of carryover, or it may be due to the presence of nucleic acid impurities that are attempting to be purified from the sample. For example, nucleic acids derived from organisms other than the organism to be detected may be present in the sample as background.

As used herein, the term "primer" refers to an oligonucleotide, whether naturally occurring (e.g., as present in a purified restriction digest product) or synthetically produced, that is capable of acting as a point of initiation of synthesis when placed under conditions that induce synthesis of a primer extension product that is complementary to a nucleic acid strand (i.e., in the presence of nucleotides and an inducing substance (e.g., a DNA polymerase) and at a suitable temperature and pH). The primer is preferably single stranded for maximum efficiency in amplification, but alternatively may be double stranded. If double stranded, the primer is first treated to separate its strands prior to use to prepare an extension product. Preferably, the primer is an oligodeoxyribonucleotide. The primer must be long enough to prime the synthesis of extension products in the presence of the inducer substance. The exact length of the primer will depend on a number of factors, including temperature, source of primer, and use of the method.

As used herein, the term "probe" refers to an oligonucleotide (i.e., a nucleotide sequence) that is capable of hybridizing to another oligonucleotide of interest, whether naturally occurring (e.g., as found in a purified restriction digest) or produced synthetically, recombinantly or by PCR amplification. The probe may be single-stranded or double-stranded. Probes can be used to detect, identify and isolate specific gene sequences. It is contemplated that any probe used in the present invention will be labeled with any "reporter molecule" and thus may be detected in any detection system including, but not limited to, enzyme systems (e.g., ELISA and enzyme-based histochemical assays), fluorescent systems, radioactive systems, and chemiluminescent systems. It is not intended that the present invention be limited to any particular detection system or label.

As used herein, the term "target" when used in reference to a polymerase chain reaction refers to a region of nucleic acid to which a primer used in the polymerase chain reaction binds. Thus, attempts have been made to separate "targets" from other nucleic acid sequences. A "segment" is defined as a region of nucleic acid within the target sequence.

As used herein, in one embodiment, the term "polymerase chain reaction" ("PCR") refers to the methods of U.S. Pat. nos. 4,683,195, 4,683,202, and 4,965,188, incorporated by reference, including methods for increasing the concentration of a target sequence segment in a genomic DNA mixture without cloning or purification. This method for amplifying a target sequence consists of: a large excess of two oligonucleotide primers is introduced into a DNA mixture containing the desired target sequence, followed by a series of precise thermal cycles in the presence of a DNA polymerase. Both primers are complementary to respective strands of the double-stranded target sequence. To effect amplification, the mixture is denatured and the primers are then annealed to their complementary sequences within the target molecule. After renaturation, the primers are extended with polymerase, thereby forming a new pair of complementary strands. The steps of denaturation, primer renaturation and polymerase extension can be repeated many times (i.e., denaturation, renaturation and extension constitute one "cycle"; numerous "cycles" can be present) to obtain a high concentration of amplified segments of the desired target sequence. The length of the amplified segment of the desired target sequence is determined by the relative positions of the primers to each other, and thus, this length is a controllable parameter. Due to the repetitive aspects of this process, the method is referred to as the "polymerase chain reaction" (hereinafter "PCR"). Since the desired amplified segments of the target sequence become dominant sequences (in terms of concentration) in the mixture, they are said to be "PCR amplified".

As used herein, the term "amplification reagents" refers to those reagents (deoxyribonucleotide triphosphates, buffers, etc.) required for amplification in addition to primers, nucleic acid template, and amplification enzyme. Generally, amplification reagents are placed and incorporated into a reaction vessel (test tube, microwell, etc.) along with other reaction components.

Using PCR, a single copy of a particular target sequence in genomic DNA can be amplified to several different methodologies (e.g., hybridization to a labeled probe; incorporation of a biotinylated primer followed by avidin-enzyme conjugate detection; will³²Incorporation of P-labeled deoxynucleotide triphosphates such as dCTP or dATP into the amplified segment). In addition to genomic DNA, any oligonucleotide or polynucleotide sequence may be amplified using a suitable set of primer molecules. In particular, the amplified segment produced by the PCR method itself is itself a useful template for subsequent PCR amplification.

As used herein, the terms "PCR product," "PCR fragment," and "amplification product" refer to a mixture of compounds resulting after two or more rounds of denaturation, renaturation, and extension PCR steps have been completed. These terms include situations where one or more segments of one or more target sequences have been amplified.

As used herein, the term "RT-PCR" refers to the replication and amplification of RNA sequences. In this method, reverse transcription is coupled to PCR, most often using a single enzyme method in which a thermostable polymerase is used, as described in U.S. patent No. 5,322,770, incorporated herein by reference. In RT-PCR, an RNA template is converted to cDNA by the reverse transcriptase activity of the polymerase, and then amplified using the polymerization activity of the polymerase (i.e., as in other PCR methods).

As used herein, the terms "restriction endonuclease" and "restriction enzyme" refer to bacterial enzymes that each cleave double-stranded DNA at or near a particular nucleotide sequence.

"restriction site" refers to a nucleotide sequence that is recognized and cleaved by a given restriction endonuclease and often serves as an insertion site for a piece of DNA. In certain embodiments of the invention, the restriction sites are engineered into the selectable marker and into the 5 'and 3' ends of the DNA construct.

As used herein, the term "chromosomal integration" refers to the process by which an entry sequence is introduced into the chromosome of a host cell. The homologous regions of the transforming DNA are aligned with the homologous regions of the chromosome. Subsequently, the sequences between the homology cassettes are replaced by the entering sequences in a double cross-over (i.e., homologous recombination). In some embodiments of the invention, the homologous portions of the inactivated chromosomal segment of the DNA construct are aligned with flanking homologous regions of the indigenous chromosomal region of the Escherichia chromosome. Subsequently, the inherent chromosomal region is deleted by the DNA construct in a double crossover (i.e., homologous recombination).

"homologous recombination" means the exchange of DNA fragments at the same or nearly the same nucleotide sequence site between two DNA molecules or paired chromosomes. In a preferred embodiment, chromosomal integration is homologous recombination. As used herein, "homologous sequence" means a nucleic acid or polypeptide sequence that has 100%, 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, 90%, 88%, 85%, 80%, 75%, or 70% sequence identity to another nucleic acid or polypeptide sequence when optimally aligned for comparison. In some embodiments, homologous sequences have between 85% and 100% sequence identity, while in other embodiments there is between 90% and 100% sequence identity, and in more preferred embodiments there is between 95% and 100% sequence identity.

As used herein, "amino acid" refers to a peptide or protein sequence or portion thereof. The terms "protein", "peptide" and "polypeptide" are used interchangeably.

As used herein, the term "heterologous protein" refers to a protein or polypeptide that does not naturally occur in a host cell. Examples of heterologous proteins include enzymes, such as isoprene synthase. In some embodiments, the gene encoding the protein is a naturally occurring gene, while in other embodiments, mutant genes and/or synthetic genes are used.

As used herein, "homologous protein" refers to a protein or polypeptide that is native or naturally occurring in a cell. In a preferred embodiment, the cell is a gram-negative cell, and in a particularly preferred embodiment, the cell is an Escherichia host cell.

An enzyme is "overexpressed" in a host cell if it is expressed in the cell at a level higher than it is expressed in the corresponding wild-type cell.

The terms "protein" and "polypeptide" are used interchangeably herein. The amino acid 3-letter code as defined by the Joint Committee for Biochemical Nomenclature (JCBN) of UPAC-IUB is used throughout the present disclosure. It is also understood that a polypeptide may be encoded by more than one nucleotide sequence due to the degeneracy of the genetic code.

The term "mature" form of a protein or peptide refers to the final functional form of the protein or peptide. For example, the mature form of pueraria isoprene synthase includes SEQ ID NO: 2.

The term "precursor" form of a protein or peptide refers to the mature form of the protein having a pre-sequence operably linked to the amino-terminus or carboxy-terminus of the protein. The precursor may also have a "signal" sequence operably linked to the amino terminus of the pro sequence. The precursor may also have additional polynucleotides involved in post-translational activity (e.g., polynucleotides cleaved therefrom to form the mature form of a protein or peptide).

"naturally-occurring enzyme" refers to an enzyme having an unmodified amino acid sequence identical to an amino acid sequence occurring in nature. Naturally occurring enzymes include native enzymes, i.e., those enzymes naturally expressed or found in a particular microorganism.

The term "identical" in the context of two nucleic acid or polypeptide sequences refers to the residues that are the same when aligned for maximum correspondence in the two sequences, as measured using one of the following sequence comparison or analysis algorithms.

The term "optimal alignment" refers to an alignment that produces the highest percent identity score.

"percent sequence identity", "percent amino acid sequence identity", "percent gene sequence identity" and/or "percent nucleic acid/polynucleotide sequence identity" in reference to two amino acid, polynucleotide and/or gene sequences (as desired) refers to the percentage of residues in the two sequences that are identical when the two sequences are optimally aligned. Thus, 80% amino acid sequence identity means that 80% of the amino acids in the two optimally aligned polypeptide sequences are identical.

The phrase "substantially identical" in the context of two nucleic acids or polypeptides thus refers to a polynucleotide or polypeptide that comprises at least 70% sequence identity, preferably at least 75%, preferably at least 80%, preferably at least 85%, preferably at least 90%, preferably at least 95%, preferably at least 97%, preferably at least 98% and preferably at least 99% sequence identity when compared to a reference sequence using a program or algorithm (e.g., BLAST, ALIGN, CLUSTAL) using standard parameters. One indication that two polypeptides are substantially identical is that the first polypeptide is immunologically cross-reactive with the second polypeptide. In general, polypeptides that differ by conservative amino acid substitutions are immunologically cross-reactive. Thus, for example, one polypeptide is substantially identical to a second polypeptide, wherein the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions (e.g., within a range of medium to high stringency).

The term "isolated" or "purified" refers to material that is removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, the substance is said to be "purified" when it is present in a particular composition at a concentration that is higher or lower than that in a naturally-occurring or wild-type organism (e.g., kudzu), or in combination with components that are not normally present when expressed from a naturally-occurring or wild-type organism. For example, a naturally occurring polynucleotide or polypeptide present in a living animal is not isolated, whereas the same polynucleotide or polypeptide, separated from some or all of the coexisting materials in the natural system, is isolated. Such polynucleotides may be part of a vector and/or such polynucleotides or polypeptides may be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment. For example, in a preferred embodiment, a nucleic acid or protein is said to be purified if it produces a substantial band in an electrophoresis gel or blot.

The term "isolated" when used in reference to a DNA sequence refers to a DNA sequence that has been removed from its natural genetic environment and thus is free of other extraneous or unwanted coding sequences, and is in a form suitable for use in a genetically engineered protein production system. The term "isolated" when used in reference to a recombinant DNA sequence refers to a DNA sequence that has been removed from the natural genetic environment of the host organism and thus does not contain other extraneous or unwanted coding sequences (e.g., the ge IspS expression vector propagated in e. Such isolated molecules are those molecules that are separate from their natural environment and include cDNA and genomic clones. The isolated DNA molecules of the invention do not contain other genes to which they normally bind, but may contain naturally occurring 5 'and 3' untranslated regions such as promoters and terminators. The identification of binding domains will be apparent to those of ordinary skill in the art (see, e.g., Dynan and Tijan, Nature 316: 774-78, 1985). The term "isolated DNA sequence" is alternatively referred to as "cloned DNA sequence".

The term "isolated" when used in reference to a protein refers to a protein that is found under conditions other than its native environment. In a preferred form, the isolated protein is substantially free of other proteins, particularly other homologous proteins. The term "isolated" when used in reference to a recombinantly produced protein refers to a protein that has been removed from the proteinaceous environment of the host organism and thus is free of other foreign or unwanted proteins (e.g., recombinant ge IspS produced in e. The isolated protein is greater than 10% pure, preferably greater than 20% pure and even more preferably greater than 30% pure as determined by SDS-PAGE. Other aspects of the invention include proteins in highly purified form (i.e., greater than 40% pure, greater than 60% pure, greater than 80% pure, greater than 90% pure, greater than 95% pure, greater than 97% pure, and even greater than 99% pure), as determined by SDS-PAGE.

The following cassette mutagenesis method may be used to aid in the construction of the enzyme variants of the invention, although other methods may be used. First, as described herein, the naturally occurring gene encoding the enzyme is obtained and sequenced in whole or in part. Subsequently, a point of the sequence is scanned, wherein a mutation (deletion, insertion or substitution) of one or more amino acids at said point is intended to be made in the encoded enzyme. The sequences flanking this point were evaluated for the presence of restriction sites intended to replace short segments of the gene with pools of oligonucleotides that, when expressed, would encode a variety of mutants. Such restriction sites are preferably unique sites within the protein gene, facilitating replacement of the gene segment. However, any convenient restriction site in the enzyme gene that is not excessively redundant may be used, provided that the gene fragments resulting from restriction digestion can be reassembled in the correct order. If a restriction site is not present at a position within a convenient distance (from 10 to 15 nucleotides) from the selected site, such a site is created by replacing nucleotides in the gene in such a way that neither the open reading frame nor the encoded amino acid is altered in the final construction. Mutation of a gene by M13 primer extension is accomplished according to widely known methods with the aim of altering its sequence to conform to a desired sequence. The task of locating the appropriate flanking regions and evaluating the changes needed to obtain two convenient restriction site sequences becomes routine through redundancy of the genetic code, restriction enzyme mapping of the gene, and a large number of different restriction enzymes. It should be noted that the above method need only be used in combination with site-free flanking regions if convenient flanking restriction sites are available.

Once the naturally occurring DNA and/or synthetic DNA is cloned, the restriction sites flanking the position to be mutated are digested with cognate restriction enzymes and a plurality of end-complementary oligonucleotide cassettes are ligated into the gene. Mutagenesis is simplified by this method because all oligonucleotides can be synthesized, thus having the same restriction sites and no synthetic linkers are required to create the restriction sites.

As used herein, "corresponding to" refers to a residue at the enumerated position in a protein or peptide, or a residue that is similar, homologous, or equivalent to the enumerated residue in a protein or peptide. As used herein, "corresponding region" generally refers to a similar position along the relevant protein or parent protein.

As used herein, the term "combinatorial mutagenesis method" refers to a method in which a library of starting sequence variants is generated. In these libraries, the variants contain one or several mutations selected from a predefined set of mutations. In addition, the method provides a means for introducing random mutations, wherein the random mutations are not members of a predefined set of mutations. In some embodiments, the methods include those described in U.S. application No. 09/699,250, which is incorporated by reference. In alternative embodiments, combinatorial mutagenesis methods include commercially available kits (e.g., the QUIKCHANGE multi-site mutagenesis kit, Stratagene, San Diego, Calif.).

As used herein, the term "mutant library" refers to a population of cells that are identical in their vast majority of genomes but that include different homologs of one or more genes. Such libraries can be used, for example, to identify genes or operons with improved traits.

As used herein, the terms "starting gene" and "parent gene" refer to a gene of interest that encodes a protein of interest to be improved and/or altered using the present invention.

As used herein, the terms "multiple sequence alignment" and "MSA" refer to sequences of multiple homologs of a starting gene aligned using an algorithm (e.g., Clustal W).

As used herein, the terms "consensus sequence" and "canonical sequence" refer to the prototype amino acid sequence to which all variants of a particular protein of interest or sequence of interest are compared. The term also refers to a sequence that gives the most frequently occurring nucleotides in a DNA sequence of interest. For each position of a gene, the consensus sequence gives the most common amino acid within that position in the MSA.

As used herein, the term "consensus mutation" refers to a difference in the sequence of the starting gene and the consensus sequence. Consensus mutations were identified by comparing the sequences of the starting gene and the consensus sequence obtained from MSA. In some embodiments, consensus mutations are introduced into the starting genes such that the starting genes become more similar to the consensus sequence. Consensus mutations also include amino acid changes that change an amino acid in the starting gene to an amino acid that is present at that position in the MSA more frequently than the frequency of that amino acid in the starting gene. Thus, the term "consensus mutation" encompasses all single amino acid changes that replace an amino acid of the starting gene with an amino acid that is more abundant than the amino acid in the MSA.

The terms "modified sequence" and "modified gene" are used interchangeably herein to refer to a sequence that includes a deletion, insertion or interruption of a naturally occurring nucleic acid sequence. In some preferred embodiments, the expression product of the modified sequence is a truncated protein (e.g., where the modification is a deletion or disruption of the sequence). In some particularly preferred embodiments, such truncated proteins still retain biological activity. In alternative embodiments, the expression product of the modified sequence is an extended protein (e.g., a protein comprising a modification of an insertion in the nucleic acid sequence). In some embodiments, the insertion results in a truncated protein (e.g., when the insertion results in the formation of a stop codon). Thus, insertions may result in truncated proteins or extended proteins as expression products.

As used herein, the terms "mutant sequence" and "mutant gene" are used interchangeably and refer to a sequence having a change in at least one codon that occurs in the wild-type sequence of the host cell. The expression product of the mutant sequence is a protein having an altered amino acid sequence relative to the wild type. The expression product can have altered functional capability (e.g., enhanced enzymatic activity).

The term "mutagenic primer" or "mutagenic oligonucleotide" (used interchangeably herein) is intended to refer to an oligonucleotide composition that corresponds to and is capable of hybridizing to a portion of a template sequence. In the case of mutagenic primers, which do not exactly match the template nucleic acid, the mismatch or mismatches in the primer are used to introduce the desired mutation into the nucleic acid library. As used herein, "non-mutagenic primer" or "non-mutagenic oligonucleotide" refers to an oligonucleotide composition that is an exact match to a template nucleic acid. In one embodiment of the invention, only mutagenic primers are used. In another preferred embodiment of the invention, the primers are designed such that for at least one region already comprising mutagenic primers, there is also non-mutagenic primers contained in the oligonucleotide mixture. By adding a mixture of mutagenic primers and non-mutagenic primers corresponding to at least one of said mutagenic primers, it is possible to generate a resulting nucleic acid library in which a plurality of combinatorial mutation patterns are present. For example, if it is desired that some members of the mutant nucleic acid library still retain their parental sequences at certain positions, while other members are mutated at such positions, the non-mutagenic primers provide the following capabilities: a specific level of non-mutated members within the nucleic acid library is obtained for a given residue. The methods of the invention employ mutagenic and non-mutagenic oligonucleotides which are generally between 10 and 50 bases in length, more preferably about 15 to 45 bases in length. However, it may be necessary to use primers shorter than 10 bases or longer than 50 bases to obtain the desired mutagenesis result. It is not necessary for the respective mutagenic and non-mutagenic primers to be of the same length, but only that there is an overlap in the region corresponding to the mutation to be added.

The primers may be added in a predetermined ratio according to the present invention. For example, if it is desired that the resulting library have significant levels of a particular mutation and lesser amounts of different mutations at the same or different sites, by adjusting the number of primers added, it is possible to generate a desired biased library. Alternatively, by adding a smaller or larger number of non-mutagenic primers, the frequency of generating corresponding mutations in a library of mutated nucleic acids can be modulated.

The terms "wild-type sequence" and "wild-type gene" are used interchangeably herein to refer to a sequence that is native or naturally occurring in a host cell. In some embodiments, a wild-type sequence refers to a sequence of interest that is the starting point of a protein engineering project. This wild-type sequence may encode a homologous or heterologous protein. Homologous proteins are proteins that the host cell will produce without intervention. Heterologous proteins are proteins that are not produced by the host cell but are produced by intervention.

As used herein, the term "lysate" refers to a solution containing the contents of lysed cells. In some embodiments, the lysate is a bacterial cell lysate (e.g., using READYLYSE from Epicentre^TME.coli cells lysed with lysozyme solution; or E.coli cells lysed using a French press).

The term "lysozyme" as used herein refers to a glucosidase enzyme that hydrolyzes the bond between N-acetylmuramic acid and N-acetylglucosamine, thereby cleaving important polymers in the cell wall of many bacteria. Suitable lysozymes for use with the present invention include, but are not limited to, egg white lysozyme (Sigma), T4 lysozyme, recombinant non-mammalian non-avian lysozyme (READYLYSE)^TM) Or fungal lysozyme.

As used herein, the term "headspace" refers to a vapor/air mixture trapped above a solid or liquid sample in a sealed container.

As used herein, the terms "high throughput screening" and "HTS" refer to the measurement of isoprene in at least 96 samples in 4 hours or less. In a preferred embodiment, the sample volume is less than 2 mL.

Unless otherwise specified, the level of an overall component or composition refers to the effective level of that component or composition and excludes impurities, such as residual solvents or by-products, which may be present in commercially available materials.

The enzyme component weight is based on total active protein. Unless otherwise stated. All percentages and ratios are by weight. All percentages and ratios are calculated based on the total composition, unless otherwise indicated.

Detailed Description

Isoprene monomer is used in the manufacture of polyisoprene and various copolymers (with isobutylene, butadiene, styrene or other monomers). To create strains (prokaryotic or eukaryotic) that are capable of producing commercially viable levels of isoprene requires optimization of the entire route from MVA to isoprene or DXP to isoprene. One key enzyme in this pathway is isoprene synthase (IspS), which converts the precursor DMAPP to isoprene. The isoprene synthases identified to date (IspS) are only those from plants such as poplar, quercus europaea and kudzu. Although some bacteria (such as bacillus subtilis) also produce isoprene, prokaryotic IspS remains to be identified and the natural IspS activity in bacillus is not sufficient for commercial processes. The plant IspS enzymes identified thus far have been characterized locally, in part, by expression in e.coli, and some kinetic parameters of these enzymes have been determined in vitro using purified proteins. However, the kinetic parameters (Km, rate, etc.) of the native IspS enzyme are not sufficient for commercial production of isoprene in a biological host.

To address this issue as described herein, plant IspS are expressed in bacterial hosts. In addition, the IspS are engineered to alter the properties of interest. Characterization of the wild-type and mutant IspS is achieved by any means or suitable "assay" and is preferably based on an assessment of the property of interest. Characteristics of interest include, but are not limited to: pH optimum, temperature stability (e.g., T) _mValue), intracellular and extracellular solubility, K_mValue, k_catValue or specific activity, and sensitivity to potential inhibitors (including substrates) or product inhibition. Oxidative stability and proteolytic stability are also objectivesAnd (4) characteristics. In addition, activation or inhibition due to the metal ion effect and ionic strength is an aimed property. These properties and parameters can be assessed by converting DMAPP to isoprene in vitro with purified or partially purified isoprene synthase or in vivo in the context of a host organism (e.g., e.coli) expressing the DXP pathway, MVA pathway, or both. It is contemplated that enzymes having various degrees of stability, solubility, activity and/or expression levels under one or more assay conditions will be used in the present invention to produce isoprene in a variety of hosts. High throughput methods to study these properties in an economical manner, such as those described in example 10, are needed.

Compositions and methods for producing increased amounts of isoprene are described. In particular, these compositions and methods increase the rate of isoprene production and increase the total amount of isoprene produced. The biosynthetic method for isoprene production described herein is a desirable alternative to using natural rubber. As discussed further below, the amount of isoprene produced by a cell can be substantially increased by introducing into the cell a heterologous nucleic acid encoding an isoprene synthase (IspS) polypeptide. The isoprene synthase polypeptide converts dimethylallyl Diphosphate (DMAPP) to isoprene. As shown in the examples, heterologous kudzu isoprene synthase polypeptides and variants thereof are expressed in gram-negative bacterial cells (e.g., e.coli). Expression of poplar isoprene synthase polypeptides and variants thereof in gram-negative bacterial cells (e.g., E.coli) is also shown in the examples and contemplated within the scope of the invention.

Heterologous expression of a plant IspS in a bacterial host cell results in the production of more isoprene than a corresponding cell lacking the plant IspS.

It has been shown that mutating amino acid residues on the surface of proteases may improve the activity, expression and stability of the enzymes (WO2008/153925, WO2008/153934, WO 2008/153935). Surprisingly, we have found that mutating amino acid residues on the surface of a completely different enzyme, i.e. isoprene synthase, can enhance the expression, solubility and activity of the enzyme. L70R is an example of such a beneficial surface mutation.

Elucidation of the three-dimensional structure of an enzyme is essential for the precise identification of amino acid residues on its surface. Homology modeling using structures having sequences that are approximately 40% identical to isoprene synthase enzymes (e.g., bornyl synthase and limonene synthase, enzymes with known structures that have the closest identity to isoprene synthase) can reveal general aspects of the modeled structures, but is not sufficient to accurately identify surface-exposed residues and quantify their degree of surface exposure. Surface exposure of an amino acid residue is quantified by the percentage of its side chain's surface area accessible to solvent.

The following classification of mutations in isoprene synthase can improve the solubility of the enzyme by targeting amino acid residues that are > 50%, preferably > 65% and most preferably > 85% solvent exposed:

hydrophobic → positively charged, and vice versa

Hydrophobic → negatively charged, and vice versa

Hydrophobic → neutral polarity, and vice versa

Neutral polarity → positively charged, and vice versa

Neutral polarity → negatively charged and vice versa

Positively charged → negatively charged, and vice versa

In addition, isoprene production by a cell containing a heterologous isoprene synthase nucleic acid can be enhanced by increasing the amount of a 1-deoxy-D-xylulose 5-phosphate synthase (DXS) polypeptide and/or Isopentenyl Diphosphate Isomerase (IDI) polypeptide expressed by the cell. For example, DXS nucleic acid and/or IDI nucleic acid may be introduced into the cell. The DXS nucleic acid may be a heterologous nucleic acid or a duplicate copy of an endogenous nucleic acid. Similarly, the IDI nucleic acid may be a heterologous nucleic acid or a duplicate copy of an endogenous nucleic acid. In some embodiments, the amount of DXS and/or IDI polypeptides is increased by replacing DXS and/or IDI endogenous promoters or regulatory regions with other promoters and/or regulatory regions that result in greater transcription of DXS and/or IDI nucleic acids. In some embodiments, the cells contain a heterologous nucleic acid encoding an isoprene synthase polypeptide (e.g., a plant isoprene synthase nucleic acid) and duplicate copies of an endogenous nucleic acid encoding an isoprene synthase polypeptide.

The encoded DXS and IDI polypeptides are part of the DXP pathway for the biosynthesis of isoprene (fig. 15). The DXS polypeptide converts pyruvate and D-glyceraldehyde-3-phosphate to 1-deoxy-D-xylulose 5-phosphate. While not intending to be bound by any particular theory, it is believed that increasing the amount of DXS polypeptide increases carbon flux through the DXP pathway, resulting in greater isoprene production. The IDI polypeptides catalyze the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl Diphosphate (DMAPP). While not intending to be bound by any particular theory, it is believed that increasing the amount of IDI polypeptide in the cell increases the amount of IPP that is converted to DMAPP, which in turn is converted to isoprene.

In some embodiments, isoprene production by a cell containing a heterologous isoprene synthase nucleic acid can be enhanced by increasing expression of a MVA polypeptide in the cell (fig. 15). Exemplary MVA pathway polypeptides include any of the following: acetyl-CoA acyltransferase (AA-CoA thiolase) polypeptides, 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) polypeptides, 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) polypeptides, mevalonate kinase (MVK) polypeptides, phosphomevalonate kinase (PMK) polypeptides, mevalonate decarboxylase diphosphate (MVD) polypeptides, IDI polypeptides, and polypeptides having the activity of two or more MVA pathway polypeptides (e.g., fusion polypeptides). For example, one or more MVA pathway nucleic acids can be introduced into the cell. In some embodiments, the cell contains a supra MVA pathway that includes an AA-CoA thiolase nucleic acid, an HMG-CoA synthase nucleic acid, and an HMG-CoA reductase nucleic acid. In some embodiments, the cell contains the following MVA pathway comprising MVK nucleic acids, PMK nucleic acids, MVD nucleic acids, and IDI nucleic acids. In some embodiments, the cell contains the entire MVA pathway, which pathway includes AA-CoA thiolase nucleic acids, HMG-CoA synthase nucleic acids, HMG-CoA reductase nucleic acids, MVK nucleic acids, PMK nucleic acids, MVD nucleic acids, and IDI nucleic acids. The MVA pathway nucleic acid can be a heterologous nucleic acid or a duplicate copy of an endogenous nucleic acid. In some embodiments, the amount of one or more MVA pathway polypeptides is increased by replacing endogenous promoter or regulatory regions of MVA pathway nucleic acids with other promoter and/or regulatory regions that result in more transcription of the MVA pathway nucleic acids. In some embodiments, the cells contain a heterologous nucleic acid encoding an isoprene synthase polypeptide (e.g., a plant isoprene synthase nucleic acid) and duplicate copies of an endogenous nucleic acid encoding an isoprene synthase polypeptide.

In some embodiments, at least a portion of the cells retain at least about 5, 10, 20, 50, 75, 100, 200, 300 or more cell divisions of the heterologous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, and/or MVA pathway nucleic acid in continuous culture (e.g., continuous culture without dilution). In some embodiments of any aspect of the invention, the nucleic acid comprising a heterologous or duplicate copy of an endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, and/or MVA pathway nucleic acid also comprises a selectable marker such as kanamycin, ampicillin, carbenicillin, gentamicin, hygromycin, phleomycin, bleomycin, neomycin, or chloramphenicol antibiotic resistance nucleic acid.

I. Exemplary Polypeptides and nucleic acids

Various isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides and nucleic acids can be used in the compositions and methods of the invention.

As used herein, "polypeptide" includes polypeptides, proteins, peptides, polypeptide fragments, and fusion polypeptides comprising part or all of a first polypeptide (e.g., an isoprene synthase, DXS, IDI, or MVA pathway polypeptide) and part or all of a second polypeptide (e.g., a peptide that aids in purification or detection of the fusion polypeptide, such as a His tag). In some embodiments, the fusion polypeptide has the activity of two or more MVA pathway polypeptides (e.g., AA-CoA thiolase and an HMG-CoA reductase polypeptide). In some embodiments, the polypeptide is a naturally occurring polypeptide having two or more MVA pathway polypeptide activities (e.g., a polypeptide encoded by an enterococcus faecalis mvaE nucleic acid).

In various embodiments, the polypeptide has at least or about 50, 100, 150, 175, 200, 250, 300, 350, 400 or more amino acids. In some embodiments, a polypeptide fragment contains at least or about 25, 50, 75, 100, 150, 200, 300, or more contiguous amino acids from a full-length polypeptide and has at least or about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, or 100% activity of the corresponding full-length polypeptide. In particular embodiments, the polypeptide comprises a segment or the entire amino acid sequence of any naturally occurring isoprene synthase, DXS, IDI, or MVA pathway polypeptide. In some embodiments, the polypeptide has one or more mutations compared to the sequence of a wild-type isoprene synthase, DXS, IDI, or MVA pathway polypeptide (i.e., a sequence found in nature).

In some embodiments, the polypeptide is an isolated polypeptide. As used herein, an "isolated polypeptide" is not part of a polypeptide library (e.g., a library of 2, 5, 10, 20, 50 or more different polypeptides) and is separate from at least one component with which it coexists in nature. An isolated polypeptide can be obtained, for example, by expressing a recombinant nucleic acid encoding the polypeptide.

In some embodiments, the polypeptide is a heterologous polypeptide. By "heterologous polypeptide" is meant a polypeptide wherein the amino acid sequence of the polypeptide is identical to the amino acid sequence of another polypeptide naturally expressed in the same host cell.

As used herein, "nucleic acid" refers to two or more deoxyribonucleotides and/or ribonucleotides in either single-or double-stranded form. In some embodiments, the nucleic acid is a recombinant nucleic acid. "recombinant nucleic acid" means a nucleic acid of interest that is free of one or more nucleic acids (e.g., genes) flanking the nucleic acid of interest in the genome of the organism from which the nucleic acid of interest is derived as it occurs in nature. The term thus includes, for example, recombinant DNA incorporated into a vector independently of other sequences, into an autonomously replicating plasmid or virus or into the genomic DNA of a prokaryote or eukaryote or which exists as a separate molecule (e.g., a cDNA, a genomic DNA fragment or a cDNA fragment produced by PCR or restriction endonuclease digestion).

In various embodiments, the nucleic acid is a recombinant nucleic acid. For example, in some embodiments, an isoprene synthase nucleic acid, DXS nucleic acid, IDI or MVA pathway nucleic acid is operably linked to another nucleic acid encoding all or part of another polypeptide, such that the recombinant nucleic acid encodes a fusion polypeptide comprising all or part of an isoprene synthase, DXS, IDI or MVA pathway polypeptide and another polypeptide (e.g., a peptide, such as a His tag, that aids in purification or detection of the fusion polypeptide). In some embodiments, part or all of the recombinant nucleic acid is chemically synthesized. In some embodiments, the nucleic acid is a heterologous nucleic acid. By "heterologous nucleic acid" is meant a nucleic acid whose nucleic acid sequence differs from that of another nucleic acid naturally found in the same host cell.

In particular embodiments, the nucleic acid comprises a segment or complete nucleic acid sequence of any naturally occurring isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid. In some embodiments, the nucleic acid comprises at least or about 50, 100, 150, 200, 300, 400, 500, 600, 700, 800 or more contiguous nucleotides from a naturally occurring isoprene synthase nucleic acid DXS, IDI, or MVA pathway nucleic acid. In some embodiments, the nucleic acid has one or more mutations compared to the wild-type sequence of the isoprene synthase, DXS, IDI, or MVA pathway nucleic acid (i.e., a sequence found in nature). In some embodiments, the nucleic acid has one or more mutations (e.g., silent mutations) that increase transcription or translation of an isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid. In some embodiments, the nucleic acid is a degenerate variant of any nucleic acid encoding an isoprene synthase, DXS, IDI, or MVA pathway polypeptide.

"codon degeneracy" refers to a divergence in the genetic code that allows variation in nucleotide sequence without affecting the amino acid sequence of an encoded polypeptide. The skilled artisan is well familiar with the "codon bias" that a particular host cell exhibits in the codon usage of nucleotides indicative of a given amino acid. Thus, when synthesizing a nucleic acid for improved expression in a host cell, it is desirable in some embodiments to design the nucleic acid such that its codon usage frequency is close to the preferred codon usage frequency of the host cell.

Accession numbers for exemplary isoprene synthase DXS, IDI, and/or MVA pathway polypeptides and nucleic acids are listed in appendix 1 of U.S. application No. 61/013,574, which is incorporated herein by reference in its entirety, particularly with respect to the amino acid and nucleic acid sequences of isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides and nucleic acids. The Kegg database also contains the amino acid and nucleic acid sequences of a number of exemplary isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides and nucleic acids (see, e.g., at and in the internet "genome. jp/Kegg/pathway/map 00100.html," which are each incorporated by reference in their entirety, particularly with respect to the amino acid and nucleic acid sequences of isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides and nucleic acids). In some embodiments, the one or more isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides and/or nucleic acids have sequence identity to a sequence that is publicly available on 12 th 2007 (e.g., any sequence corresponding to any accession number in annex 1 of U.S. application No. 61/013,574 or any sequence present in the Kegg database by the date of filing of the present application). Additional exemplary isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides and nucleic acids are described further below.

Exemplary isoprene synthase Polypeptides and nucleic acids

As described above, the isoprene synthase polypeptide converts dimethylallyl Diphosphate (DMAPP) to isoprene. Exemplary isoprene synthase polypeptides include at least one activity with an isoprene synthase polypeptideSex polypeptides, polypeptide fragments, peptides and fusion polypeptides. Standard methods can be used to determine whether a polypeptide has isoprene synthase polypeptide activity by measuring the ability of the polypeptide to convert DMAPP to isoprene in vitro, in a cell extract, or in vivo. Isoprene synthase polypeptide activity in cell extracts can be found, for example, in Silver et al, j.biol.chem.270: 13010-13016, 1995 and references, each of which is hereby incorporated by reference in their entirety, particularly in assays for isoprene synthase polypeptide activity. DMAPP (Sigma) was evaporated to dryness under a stream of nitrogen and rehydrated to a concentration of 100mM in 100mM potassium phosphate buffer pH 8.2 and stored at-20 ℃. To perform the assay, 5. mu.l of 1M MgCl will be included₂1mM (250. mu.g/ml) DMAPP, 65. mu.l Plant Extraction Buffer (PEB) (50mM Tris-HCl, pH 8.0, 20mM MgCl₂5% glycerol and 2mM DTT) was added to 25. mu.l of cell extract in a 20ml headspace vial (Agilent Technologies) with a metal screw cap and Teflon coated silicon septum and incubated for 15 minutes at 37 ℃ with shaking. The reaction was terminated by the addition of 200. mu.l of 250mM EDTA or by heat inactivation and isoprene was quantified by GC/MS.

Exemplary isoprene synthase nucleic acids include nucleic acids encoding polypeptides, polypeptide fragments, peptides, and fusion polypeptides having at least one activity of an isoprene synthase polypeptide. Exemplary isoprene synthase polypeptides and nucleic acids include naturally-occurring polypeptides and nucleic acids from any of the source organisms described herein as well as mutant polypeptides and nucleic acids derived from any of the source organisms described herein.

In some embodiments, the isoprene synthase polypeptide or nucleic acid is from the family leguminosae (Fabaceae), Salicaceae (Salicaceae), or Fagaceae (Fagaceae). In some embodiments, the isoprene synthase polypeptide or nucleic acid is a naturally occurring polypeptide or nucleic acid from Pueraria lobata (Kudzuvine) (Sharkey et al, Plant Physiology 137: 700-. Suitable isoprene synthases include, but are not limited to, those pentadiene synthases identified by GenBank accession nos. AY341431, AY316691, AY279379, AY 457070 and AY182241, which are thus each incorporated by reference in their entirety, particularly with respect to the sequence of isoprene synthase nucleic acids and polypeptides. In some embodiments, the isoprene synthase polypeptide or nucleic acid is not a naturally-occurring polypeptide or nucleic acid from quercus robur (i.e., the isoprene synthase polypeptide or nucleic acid is an isoprene synthase polypeptide or nucleic acid other than a naturally-occurring polypeptide or nucleic acid from quercus robur). In some embodiments, the isoprene synthase nucleic acid or polypeptide is not a naturally occurring polypeptide or nucleic acid from poplar (e.g., populus alba x populus tremula CAC 35696).

Exemplary DXS polypeptides and nucleic acids

As described above, the 1-deoxy-D-xylulose 5-phosphate synthase (DXS) polypeptide converts pyruvate and D-glyceraldehyde 3-phosphate to 1-deoxy-D-xylulose 5-phosphate. Exemplary DXS polypeptides include polypeptides, polypeptide fragments, peptides, and fusion polypeptides having at least one activity of a DXS polypeptide. Standard methods (such as those described herein) can be used to determine whether a polypeptide has DXS polypeptide activity by measuring the ability of the polypeptide to convert pyruvate and D-glyceraldehyde-3-phosphate to 1-deoxy-D-xylulose-5-phosphate in vitro, in cell extracts, or in vivo. Exemplary DXS nucleic acids include nucleic acids encoding polypeptides, polypeptide fragments, peptides, and fusion polypeptides having at least one activity of a DXS polypeptide. Exemplary DXS polypeptides and nucleic acids include naturally occurring polypeptides and nucleic acids from any of the source organisms described herein as well as mutant polypeptides and nucleic acids derived from any of the source organisms described herein.

Exemplary IDI Polypeptides and nucleic acids

Isopentenyl diphosphate isomerase polypeptides (isopentenyl diphosphate delta-isomerase or IDI) catalyze the interconversion of isopentenyl diphosphate (IPP) and dimethylallyl Diphosphate (DMAPP) (e.g., conversion of IPP to DMAPP and/or DMAPP to IPP). Exemplary IDI polypeptides include polypeptides, polypeptide fragments, peptides, and fusion polypeptides having at least one activity of an IDI polypeptide. Standard methods (such as those described herein) can be used to determine whether a polypeptide has IDI polypeptide activity by measuring the ability of the polypeptide to interconvert IPP with DMAPP in vitro, in a cell extract, or in vivo. Exemplary IDI nucleic acids include nucleic acids encoding polypeptides, polypeptide fragments, peptides, and fusion polypeptides having at least one activity of an IDI polypeptide. Exemplary IDI polypeptides and nucleic acids include naturally occurring polypeptides and nucleic acids from any of the source organisms described herein as well as mutant polypeptides and nucleic acids derived from any of the source organisms described herein.

Exemplary MVA pathway polypeptides and nucleic acids

Exemplary MVA pathway polypeptides include: acetyl-CoA acyltransferase (AA-CoA thiolase) polypeptides, 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase) polypeptides, 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) polypeptides, mevalonate kinase (MVK) polypeptides, phosphomevalonate kinase (PMK) polypeptides, mevalonate decarboxylase diphosphate (MVD) polypeptides, IDI polypeptides, and polypeptides having the activity of two or more MVA pathway polypeptides (e.g., fusion polypeptides). In particular, MVA pathway polypeptides include polypeptides, polypeptide fragments, peptides, and fusion polypeptides having at least one activity of a MVA pathway polypeptide. Exemplary MVA pathway nucleic acids include nucleic acids encoding polypeptides, polypeptide fragments, peptides, and fusion polypeptides having at least one activity of a MVA pathway polypeptide. Exemplary MVA pathway polypeptides and nucleic acids include naturally occurring polypeptides and nucleic acids from any of the source organisms described herein as well as mutant polypeptides and nucleic acids derived from any of the source organisms described herein.

In particular, an acetyl-CoA acyltransferase polypeptide (AA-CoA thiolase or AACT) converts two molecules of acetyl-CoA into acetoacetyl-CoA. Standard methods (such as those described herein) can be used to determine whether a polypeptide has AA-CoA thiolase polypeptide activity by measuring the ability of the polypeptide to convert two molecules of acetyl-CoA to acetoacetyl-CoA in vitro, in a cell extract, or in vivo.

A 3-hydroxy-3-methylglutaryl-CoA synthase (HMG-CoA synthase or HMGs) polypeptide converts acetoacetyl-CoA to 3-hydroxy-3-methylglutaryl-CoA. Standard methods (such as those described herein) can be used to determine whether a polypeptide has HMG-CoA synthase polypeptide activity by measuring the ability of the polypeptide to convert acetoacetyl-CoA to 3-hydroxy-3-methylglutaryl-CoA in vitro, in a cell extract, or in vivo.

A 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase or HMGR) polypeptide converts 3-hydroxy-3-methylglutaryl-CoA to mevalonate. Standard methods (such as those described herein) can be used to determine whether a polypeptide has HMG-CoA reductase polypeptide activity by measuring the ability of the polypeptide to convert 3-hydroxy-3-methylglutaryl-CoA to mevalonate in vitro, in a cell extract, or in vivo.

Mevalonate kinase (MVK) polypeptides phosphorylate mevalonate to form mevalonate-5-phosphate. Standard methods (such as those described herein) can be used to determine whether a polypeptide has MVK polypeptide activity by measuring the ability of the polypeptide to convert mevalonate to mevalonate-5-phosphate in vitro, in cell extracts, or in vivo.

The phosphomevalonate kinase (PMK) polypeptide phosphorylates mevalonate-5-phosphate to form mevalonate-5-diphosphate. Standard methods (such as those described herein) can be used to determine whether a polypeptide has PMK polypeptide activity by measuring the ability of the polypeptide to convert mevalonate-5-phosphate to mevalonate-5-diphosphate in vitro, in cell extracts, or in vivo.

Mevalonate diphosphate decarboxylase (MVD or DPMDC) polypeptides convert mevalonate-5-diphosphate to isopentenyl diphosphate polypeptides (IPP). Standard methods (such as those described herein) can be used to determine whether a polypeptide has MVD polypeptide activity by measuring the ability of the polypeptide to convert mevalonate-5-diphosphate to IPP in vitro, in cell extracts, or in vivo.

Exemplary methods for isolating nucleic acids

Isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids, and/or MVA pathway nucleic acids can be isolated using standard methods. Methods for obtaining the desired nucleic acid from a source organism of interest (e.g., a bacterial genome) are common and well known in the art of molecular biology (see, e.g., WO 2004/033646 and the cited references, each of which is thus incorporated by reference in its entirety, particularly in the isolation of the nucleic acid of interest). For example, if the sequence of the nucleic acid is known (as with any of the known nucleic acids described herein), a suitable genomic library can be generated by restriction endonuclease digestion and can be screened with probes complementary to the sequence of the desired nucleic acid. Once the sequence is isolated, the DNA can be amplified using standard primer directed amplification methods such as Polymerase Chain Reaction (PCR) (U.S. Pat. No. 4,683,202, which is incorporated by reference in its entirety, particularly in terms of PCR methods) to obtain an amount of DNA suitable for transformation with a suitable vector. Alternatively, an isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, and/or MVA pathway nucleic acid (e.g., any isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, and/or MVA pathway nucleic acid having a known nucleic acid sequence) can be chemically synthesized using standard methods.

Additional isoprene synthase, DXS, IDI, or MVA pathway polypeptides and nucleic acids that may be suitable for use in the compositions and methods described herein may be identified using standard methods. For example, it is known that cosmid libraries of chromosomal DNA from organisms that naturally produce isoprene can be constructed in organisms such as E.coli and subsequently screened for isoprene production. Additional methods for obtaining isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids, and/or MVA pathway nucleic acids include screening a metagenomic library by an assay (such as the headspace assay described herein) or by PCR using primers directed to nucleotides encoding conserved amino acids of a certain length (e.g., at least 3 conserved amino acids). Conserved amino acids can be identified by aligning the amino acid sequences of known isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides. Conserved amino acids of isoprene synthase polypeptides can be identified based on the aligned known isoprene synthase polypeptide sequences. It was found that organisms that naturally produce isoprene can be processed by standard protein purification methods (well known in the art) and the resulting purified polypeptide can be sequenced by standard methods. Other methods exist in the literature (see, e.g., Julising et al, applied. Microbiol. Biotechnol.75: 1377-84, 2007; and Withers et al, applied Environ Microbiol.73: 6277-83, 2007), each of which is thus incorporated by reference in its entirety, particularly in terms of the identification of nucleic acids involved in the synthesis of isoprene.

In addition, standard sequence alignment and/or structure prediction programs can be used to identify additional DXS, IDI, or MVA pathway polypeptides and nucleic acids based on the similarity of primary structure and/or predicted polypeptide secondary structure to known DXS, IDI, or MVA pathway polypeptides and nucleic acids. Standard databases such as the swissprot-tremebl database (on the Internet "expay. org", Swiss-Prot group CMU-1 rue Michel Server CH-1211 Geneva 4, Switzerland) may also be used to identify isoprene synthase, DXS, IDI or MVA pathway polypeptides and nucleic acids. Secondary and/or tertiary structures of isoprene synthase, DXS, IDI or MVA pathway polypeptides can be predicted using standard structure prediction programs such as The default settings of PredictProtein (Rost et al, The PredictProtein Server. nucleic Acids Research 32 (Web Server distribution): W321-W326, 2004). Alternatively, the actual secondary and/or tertiary structure of the isoprene synthase, DXS, IDI or MVA pathway polypeptides may be determined using standard methods. Additional isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids, or MVA pathway nucleic acids can also be identified by hybridization to probes generated from known isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids, or MVA pathway nucleic acids.

Exemplary promoters and vectors

Any of the isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids, or MVA pathway nucleic acids described herein can be comprised in one or more vectors. Thus, the invention also features vectors having one or more nucleic acids encoding any of the isoprene synthase, DXS, IDI, or MVA pathway polypeptides described herein. As used herein, "vector" means a construct capable of delivering and expressing one or more nucleic acids of interest in a host cell in a desired manner. Examples of vectors include, but are not limited to, plasmids, viral vectors, DNA or RNA expression vectors, cosmids, and phage vectors. In some embodiments, the vector contains a nucleic acid under the control of an expression control sequence.

As used herein, "expression control sequence" means a nucleic acid sequence that directs transcription of a nucleic acid of interest. The expression control sequence may be a promoter, such as a constitutive or inducible promoter, or an enhancer. An "inducible promoter" is a promoter that is active under environmental or developmental regulation. The expression control sequence is operably linked to the nucleic acid segment to be transcribed.

In some embodiments, the vector contains a selectable marker. The term "selectable marker" refers to a nucleic acid capable of being expressed in a host cell that allows for easy selection of those host cells containing the introduced nucleic acid or vector. Examples of selectable markers include, but are not limited to, antibiotic (e.g., kanamycin, ampicillin, carbenicillin, gentamicin, hygromycin, phleomycin, bleomycin, neomycin, or chloramphenicol) resistance nucleic acids and/or nucleic acids that confer a metabolic advantage, such as a nutritional advantage, on the host cell. In some embodiments, the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is integrated into the chromosome of the cell without a selectable marker.

Suitable vectors are those compatible with the host cell used. Suitable vectors may be derived, for example, from bacteria, viruses (e.g., bacteriophage T7 or M-13-derived phage), cosmids, yeast, or plants. Protocols for obtaining and using such vectors are known in the art (see, e.g., Sambrook et al, Molecular Cloning: A Laboratory Manual, 2 nd edition, Coldspring Harbor, 1989, which is incorporated herein by reference in its entirety, particularly with respect to the use of the vector).

Promoters are well known in the art. Any promoter functional in a host cell can be used to express an isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid in a host cell. Initiation regulatory regions or promoters for driving expression of isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids or MVA pathway nucleic acids in a variety of host cells are numerous and familiar to those of skill in the art (see, e.g., WO 2004/033646 and references cited therein, each of which is thus incorporated by reference in its entirety, particularly in terms of vectors for expressing nucleic acids of interest). Virtually any promoter capable of driving these nucleic acids is suitable for use in the present invention, including, but not limited to, lac, trp, λ P _L、λP_RT7, tac and trc (for expression in E.coli).

In some embodiments, a glucose isomerase promoter is used (see, e.g., U.S. Pat. No. 7,132,527 and references cited therein, each of which is thus incorporated by reference in its entirety, particularly in terms of promoters and plasmid systems for expressing a polypeptide of interest). The reported glucose isomerase promoter mutants can be used to alter the expression level of a polypeptide encoded by a nucleic acid operably linked to the glucose isomerase promoter (U.S. Pat. No. 7,132,527). In various embodiments, the glucose isomerase promoter is contained in a low, medium or high copy plasmid (U.S. Pat. No. 7,132,527).

In various embodiments, the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, and/or MVA pathway nucleic acid is comprised in a low copy plasmid (e.g., a plasmid maintained at about 1 to about 4 copies per cell), a medium copy plasmid (e.g., a plasmid maintained at about 10 to about 15 copies per cell), or a high copy plasmid (e.g., a plasmid maintained at about 50 or more copies per cell). In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to a T7 promoter. In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to a T7 promoter comprised in a medium or high copy plasmid. In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to a Trc promoter. In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to a Trc promoter comprised in a medium or high copy plasmid. In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to a Lac promoter. In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to a Lac promoter contained in a low copy plasmid. In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to an endogenous promoter, such as an escherichia, pantoea, bacillus, yarrowia, Streptomyces (Streptomyces), or trichoderma endogenous promoter or an endogenous alkaline serine protease, isoprene synthase, DXS, IDI, or MVA pathway promoter. In some embodiments, the heterologous or additional endogenous isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is operably linked to an endogenous promoter comprised in a high copy plasmid. In some embodiments, the vector is a replicative plasmid that does not integrate into the chromosome of the cell. In some embodiments, part or all of the vector is integrated into a chromosome in the cell.

In some embodiments, the expression vector also includes a termination sequence. Termination control regions may also be derived from various genes native to the host cell. In some embodiments, the termination sequence and the promoter sequence are derived from the same source. In another embodiment, the termination sequence is endogenous to the host cell.

In some embodiments, the promoter, coding region, and terminator are all derived from the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid to be expressed. In some embodiments, the coding region of the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is inserted into a universal expression vector such that the coding region is under the transcriptional control of the promoter and terminator sequences of the expression construct. In some embodiments, the gene or portion thereof is inserted downstream of a strong cbh1 promoter.

Isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid can be incorporated into vectors, such as expression vectors, using standard techniques (Sambrook et al, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor, 1982, which is incorporated herein by reference in its entirety, particularly in the context of screening for suitable DNA sequences and vector construction). Methods for ligating DNA constructs comprising a nucleic acid of interest (e.g., an isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid), a promoter, a terminator, and other sequences for their insertion into a suitable vector are well known in the art. For example, restriction enzymes can be used to cleave the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acids and vectors. Subsequently, the cleaved isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid can be ligated to compatible ends of the cleaved vector. Ligation is typically performed by ligation at convenient restriction enzyme sites. If such sites are not present, synthetic oligonucleotide linkers are used in accordance with conventional practice (see, Sambrook et al, Molecular Cloning: A Laboratory Manual, 2 nd edition, Cold Spring Harbor, 1989 and Bennett and Lasure, More Gene industries in Fungi, Academic Press, San Diego, pages 70-76, 1991, each of which is hereby incorporated by reference in its entirety, particularly in terms of oligonucleotide linkers). In addition, vectors can be constructed using known recombinant techniques (e.g., Invitrogen Life Technologies, Gateway Technology).

In some embodiments, it may be desirable to overexpress an isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid at levels much higher than those currently found in naturally occurring cells. This result can be achieved by selectively cloning nucleic acids encoding those polypeptides into multicopy plasmids or placing those nucleic acids under a strong inducible or constitutive promoter. Methods for over-expressing a desired polypeptide are common and well known in the field of Molecular biology and can be found in Sambrook et al, Molecular Cloning: a Laboratory Manual, 2 nd edition, Cold Spring Harbor, 1989 (which is incorporated herein by reference in its entirety, particularly in terms of cloning technology).

The following resources include a description of additional general methodologies useful in accordance with the present invention: kreigler, Gene Transfer and Expression; a Laboratory Manual, 1990; and Ausubel et al, Current Protocols in Molecular Biology, 1994, 1994, which are each hereby incorporated by reference in their entirety, in particular in terms of Molecular Biology and cloning technology.

Exemplary Source organisms

The isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid (and their encoding polypeptides) can be obtained from any organism that naturally contains isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, and/or MVA pathway nucleic acid. As described above, isoprene is naturally produced by various organisms such as bacteria, yeast, plants, and animals. The organisms contained either the MVA pathway, DXP pathway or both MVA and DXP pathways for producing isoprene (fig. 15). Thus, a DXS nucleic acid may be obtained, for example, from any organism containing the DXP pathway or both the MVA and DXP pathways. The IDI nucleic acids and isoprene synthase nucleic acids can be obtained, for example, from any organism containing the MVA pathway, the DXP pathway, or both the MVA and DXP pathways. MVA pathway nucleic acids can be obtained, for example, from any organism containing the MVA pathway or both the MVA and DXP pathways.

In some embodiments, the nucleic acid sequence of the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid is identical to the sequence of a nucleic acid produced in nature by any of the following organisms. In some embodiments, the amino acid sequence of the isoprene synthase, DXS, IDI, or MVA pathway polypeptide is identical to the sequence of a polypeptide produced by any of the following organisms in nature. In some embodiments, the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, or MVA pathway nucleic acid or polypeptide is a mutant nucleic acid or polypeptide derived from any of the organisms described herein. As used herein, "derived from … …" refers to the source of the nucleic acid or polypeptide into which one or more mutations have been introduced. For example, a polypeptide "derived from a plant polypeptide" refers to a polypeptide of interest that results from the introduction of one or more mutations into the sequence of a wild-type plant polypeptide (i.e., a sequence found in nature).

In some embodiments, the source organism is a bacterium, such as an escherichia strain (e.g., escherichia coli), or a bacillus strain (e.g., bacillus subtilis).

As used herein, "escherichia" includes all species within "escherichia" as known to those skilled in the art, including, but not limited to, escherichia coli, non-decarboxylated escherichia (e.adecaboxylinata), e.albertii, escherichia blattae (e.blattae), escherichia fergusonii, escherichia coli (e.hermannii), e.senegalensis, and escherichia coides (e.vulneris). "Escherichia" is defined as a gram-negative, non-sporulating, facultative anaerobic rod-shaped bacterium, classified as a member of the group of the Gamma Proteobacteria (Gamma Proteobacteria), Enterobacteriales (Enterobacteriales), Enterobacteriaceae (Enterobacteriaceae).

As used herein, "Bacillus (Bacillus)" includes all species within "Bacillus" as known to those skilled in the art, including, but not limited to, Bacillus subtilis (b), Bacillus licheniformis (b), Bacillus lentus (b), Bacillus brevis (b), Bacillus stearothermophilus (b), Bacillus alkalophilus (b), Bacillus amyloliquefaciens (b.amyloliquefaciens), Bacillus clausii (b.clausii), Bacillus halodurans (b.halodurans), Bacillus megaterium (b.megaterium), Bacillus coagulans (b.coagulans), Bacillus circulans (b.circulans), Bacillus lautus (b.lautus) and Bacillus thuringiensis (b.thuringiensis). It is recognized that the genus bacillus continues to undergo taxonomic reorganization. Thus, it is intended that the genus includes species that have been reclassified, including but not limited to such organisms as Bacillus stearothermophilus, which is now designated "Geobacillus stearothermophilus". The production of resistant endospores in the presence of oxygen is considered a defining feature of the genus Bacillus, although this feature also applies to newly named Alicyclobacillus (Alicyclobacillus), Bacillus bisporus (Amphibacillus), Thiamine bacillus (Aneurinibacillus), anaerobic bacillus (Anoxybacillus), Brevibacillus (Brevibacillus), Filobacillus, parenchyma bacillus (Gracilobacterium), Halobacterium (Halobacillus), Paenibacillus (Paenibacillus), Halobacter (Salibacillus), Thermobacillus (Thermobacillus), Ureinobacillus (Ureibacillus) and Bacillus (Virgibacillus).

Exemplary host cells

Various host cells can be used to express isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides and to produce isoprene in the methods of the claimed invention. Exemplary host cells include cells from any of the organisms listed in the previous section entitled "exemplary source organism". The host cell may be a cell that naturally produces isoprene or a cell that does not naturally produce isoprene. In some embodiments, the host cell naturally produces isoprene using the DXP pathway, and adds an isoprene synthase nucleic acid, DXS nucleic acid, and/or IDI nucleic acid to utilize the pathway to enhance isoprene production. In some embodiments, the host cell naturally produces isoprene using the MVA pathway, and an isoprene synthase nucleic acid and/or one or more MVA pathway nucleic acids are added to utilize this pathway to enhance isoprene production. In some embodiments, the host cell naturally produces isoprene using the DXP pathway, and one or more MVA pathway nucleic acids are added to produce isoprene using part or all of the MVA pathway and the DXP pathway. In some embodiments, the host cell naturally produces isoprene using the DXP and MVA pathways, and one or more isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids, or MVA pathway nucleic acids are added to enhance isoprene production using one or both of the pathways.

Exemplary transformation methods

The isoprene synthase nucleic acids, DXS nucleic acids, IDI nucleic acids, and/or MVA pathway nucleic acids, or vectors containing them, can be inserted into host cells (e.g., bacterial cells) using standard techniques for expressing the encoded isoprene synthase, DXS, IDI, and/or MVA pathway polypeptides. Introduction of the DNA construct or vector into the host cell can be carried out using techniques such as transformation; electroporation; performing intracuclear microinjection; transduction; transfection (e.g., lipofection-mediated or DEAE-dextran-mediated transfection or transfection using recombinant phage virus); incubating with calcium phosphate DNA precipitate; high-speed particle bombardment with DNA-coated microparticles and protoplast fusion were used. General transformation techniques are known in the art (see, e.g., Current Protocols in Molecular Biology (F.M. Ausubel et al (eds.) Chapter 9, 1987; Sambrook et al, Molecular Cloning: A Laboratory Manual, 2 nd edition, Cold Spring Harbor, 1989; and Campbell et al, Current Gene, 16: 53-56, 1989, each of which is hereby incorporated by reference in its entirety, particularly in terms of transformation methods.) the introduced nucleic acid can be integrated into the chromosomal DNA or maintained as an extrachromosomally replicating sequence.

Exemplary cell culture media

The invention also includes cells or cell populations that produce isoprene in culture. By "cells in culture" is meant two or more cells in a solution (e.g., cell culture medium) that allows the cells to undergo one or more cell divisions. "cells in culture" does not include plant cells that are part of a living multicellular plant containing cells that have differentiated into plant tissue. In various embodiments, the cell culture comprises at least or about 10, 20, 50, 100, 200, 500, 1,000, 5,000, 10,000 or more cells.

Any carbon source may be used to cultivate the host cell. The term "carbon source" refers to one or more carbon-containing compounds capable of being metabolized by a host cell or organism. For example, the cell culture medium used to cultivate the host cell may include any carbon source suitable for maintaining the viability or growth of the host cell.

In some embodiments, the carbon source is a saccharide (such as a monosaccharide, disaccharide, oligosaccharide, or polysaccharide), an invert sugar (e.g., an enzymatically treated sucrose syrup), glycerol (e.g., a glycerol byproduct of a biodiesel or soap manufacturing process), dihydroxyacetone, a carbon source, a fatty acid (e.g., a saturated fatty acid, an unsaturated fatty acid, or a polyunsaturated fatty acid), a lipid, a phospholipid, a glyceride, a monoglyceride, a diglyceride, a triglyceride, a polypeptide (e.g., a microbial or plant protein or peptide), a renewable carbon source (e.g., a biomass carbon source such as a hydrolyzed biomass carbon source; beet molasses or cane molasses), a yeast extract, a component from a yeast extract, a polymer, an acid, an alcohol, an aldehyde, a ketone, an amino acid, succinic acid, lactic acid, acetic acid, ethanol, or any combination of two or more of the foregoing. In some embodiments, the carbon source is a product of photosynthesis, including, but not limited to, glucose.

Exemplary monosaccharides include glucose and fructose; exemplary oligosaccharides include lactose and sucrose, and exemplary polysaccharides include starch and cellulose. Exemplary sugars include C6 sugars (e.g., fructose, mannose, galactose, or glucose) and C5 sugars (e.g., xylose or arabinose). In some embodiments, the cell culture medium includes sugars and a carbon source other than sugars (e.g., glycerol, dihydroxyacetone, a carbon source, fatty acids, lipids, phospholipids, glycerides, monoglycerides, diglycerides, triglycerides, a renewable carbon source, or a component from a yeast extract). In some embodiments, the cell culture medium includes carbohydrates as well as polypeptides (e.g., microbial or plant proteins or peptides). In some embodiments, the microbial polypeptide is a polypeptide from a yeast or a bacterium. In some embodiments, the plant polypeptide is a polypeptide from soybean, corn, canola, jatropha, palm, peanut, sunflower, coconut, mustard, rapeseed, cottonseed, palm kernel, olive, safflower, sesame, or linseed.

In some embodiments, the concentration of saccharide is at least or about 5 grams per liter of broth (g/L, wherein the volume of the broth includes the volume of cell culture medium and the volume of the cells), such as at least or about 10, 15, 20, 30, 40, 50, 60, 80, 100, 150, 200, 300, 400, or more g/L. In some embodiments, the concentration of saccharide is between about 50 and about 400g/L, such as between about 100 and about 360g/L, between about 120 and about 360g/L, or between about 200 and about 300 g/L. In some embodiments, this concentration of saccharide includes the total amount of saccharide added before and/or during culturing of the host cell.

Exemplary lipids are any material containing one or more fatty acids, wherein the fatty acid is a saturated, unsaturated, or branched fatty acid of C4 and above.

Exemplary fatty acids include compounds of the formula R-COOH, wherein "R" is a hydrocarbon. Exemplary unsaturated fatty acids include compounds wherein "R" comprises at least one carbon-carbon double bond. Exemplary unsaturated fatty acids include, but are not limited to, oleic acid, 11-octadecenoic acid, linoleic acid, palmitoleic acid (palmitelaidic acid), and arachidonic acid. Exemplary polyunsaturated fatty acids include compounds in which "R" comprises multiple carbon-carbon double bonds. Exemplary saturated fatty acids include compounds wherein "R" is a saturated aliphatic group. In some embodiments, the carbon source comprises one or more C₁₂-C₂₂Fatty acids, e.g. C₁₂Saturated fatty acid, C₁₄Saturated fatty acid, C₁₆Saturated fatty acid, C₁₈Saturated fatty acid, C₂₀Saturated fatty acids or C₂₂A saturated fatty acid. In an exemplary embodiment, the fatty acid is palmitic acid. In some embodiments, the carbon source is a salt of a fatty acid (e.g., an unsaturated fatty acid), a derivative of a fatty acid (e.g., an unsaturated fatty acid), or a salt of a derivative of a fatty acid (e.g., an unsaturated fatty acid). Suitable salts include, but are not limited to, lithium Salts, potassium salts, sodium salts, and the like. Diglycerides and triglycerides are fatty acid esters of glycerol.

In some embodiments, the concentration of the lipid, fatty acid, monoglyceride, diglyceride, or triglyceride is at least or about 1 gram per liter of culture fluid (g/L, wherein the volume of culture fluid includes the volume of cell culture medium and the volume of cells), such as at least or about 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, 150, 200, 300, 400, or more g/L. In some embodiments, the concentration of lipids, fatty acids, monoglycerides, diglycerides, or triglycerides is between about 10 and about 400g/L, such as between about 25 and about 300g/L, between about 60 and about 180g/L, or between about 75 and about 150 g/L. In some embodiments, the concentration includes the total amount of lipids, fatty acids, monoglycerides, diglycerides, or triglycerides added before and/or during culturing of the host cell. In some embodiments, the carbon source comprises (i) a lipid, fatty acid, monoglyceride, diglyceride, or triglyceride and (ii) a saccharide, such as glucose. In some embodiments, the ratio of lipid, fatty acid, monoglyceride, diglyceride, or triglyceride to carbohydrate is about 1: 1 on a carbon basis (i.e., one carbon of lipid, fatty acid, monoglyceride, diglyceride, or triglyceride/carbohydrate carbon). In particular embodiments, the amount of lipid, fatty acid, monoglyceride, diglyceride, or triglyceride is between about 60 and 180g/L and the amount of sugar is between about 120 and 360 g/L.

Exemplary microbial polypeptide carbon sources include one or more polypeptides from yeast or bacteria. Exemplary plant polypeptide carbon sources include one or more polypeptides from soybean, corn, canola, jatropha, palm, peanut, sunflower, coconut, mustard, rapeseed, cottonseed, palm kernel, olive, safflower, sesame, or flax.

Exemplary renewable carbon sources include cheese whey permeate, corn steep liquor, beet molasses, barley malt, and components from any of the foregoing. Exemplary renewable carbon sources also include glucose, hexoses, pentoses, and xylose present in biomass (e.g., corn, switchgrass, sugar cane, cellular waste of fermentation processes, and protein by-products from milling of soybeans, corn, or wheat). In some embodiments, the biomass carbon source is a lignocellulosic, hemicellulosic, or cellulosic material, such as, but not limited to, grasses, wheat straw, bagasse, beet pulp, softwood pulp, corn cobs or corn husks, corn kernels, fiber from corn kernels, corn stover, switchgrass, rice hull products, or byproducts from grain dry and wet milling (e.g., corn, sorghum, rye, triticale, barley, wheat, and/or distillers grains). Exemplary cellulosic materials include wood, paper and pulp waste, herbs and fruit pulp. In some embodiments, the carbon source comprises any plant part, such as a stem, grain, root, or tuber. In some embodiments, all or part of any of the following plants is used as a carbon source: maize, wheat, rye, sorghum, triticale, rice, millet, barley, cassava, legumes, such as beans and peas, potatoes, sweet potatoes, bananas, sugar cane and/or cassava. In some embodiments, the carbon source is a biomass hydrolysate, such as a biomass hydrolysate comprising xylose and glucose and comprising sucrose and glucose.

In some embodiments, the renewable carbon source (e.g., biomass) is pretreated prior to addition to the cell culture medium. In some embodiments, the pretreatment comprises enzymatic pretreatment, chemical pretreatment, or a combination of enzymatic and chemical pretreatment (see, e.g., Farzaneh et al, Bioresource Technology 96 (18): 2014-2018, 2005; U.S. Pat. No. 6,176,176; U.S. Pat. No. 6,106,888; each of which is thus incorporated by reference in its entirety, particularly with respect to the pretreatment of renewable carbon sources). In some embodiments, the renewable carbon source is partially or completely hydrolyzed prior to addition to the cell culture medium.

In some embodiments, the renewable carbon source (e.g., corn stover) is subjected to an Ammonia Fiber Expansion (AFEX) pretreatment prior to addition to the cell culture medium (see, e.g., Farzaneh et al, Biosource Technology 96 (18): 2014-2018, 2005). During the AFEX pretreatment, the renewable carbon source is treated with anhydrous liquid ammonia at mild temperatures (e.g., about 60 to about 100 ℃) and high pressures (e.g., about 250 to about 300psi) for about 5 minutes. Subsequently, the pressure was released rapidly. In this process, the combined chemical and physical effects of lignin solubilization, hemicellulose hydrolysis, cellulose decrystallization, and increased surface area allow for near complete enzymatic conversion of cellulose and hemicellulose to fermentable sugars. AFEX pretreatment has the advantage that all ammonia can be recovered and reused while the residue serves as a nitrogen source for microorganisms in downstream processes. In addition, AFEX pretreatment does not require a wash stream. Thus, the dry matter recovery after AFEX treatment is essentially 100%. AFEX is a substantially dry-to-dry process. The treated renewable carbon source is stable for long periods of time and can be dosed at high solids loadings during enzymatic hydrolysis or fermentation. Cellulose and hemicellulose are well protected with little or no degradation during AFEX. Neutralization is not required before enzymatically hydrolyzing the renewable carbon source that has been pretreated with AFEX. Enzymatic hydrolysis of AFEX treated carbon source produces a clean sugar stream for subsequent fermentation use.

In some embodiments, the concentration of the carbon source (e.g., renewable carbon source) is equivalent to at least or about 0.1, 0.5, 1, 1.5, 2, 3, 4, 5, 10, 15, 20, 30, 40, or 50% glucose (w/v). Equivalent amounts of glucose can be determined by measuring the amount of glucose produced from the carbon source using standard HPLC methods with glucose as a reference. In some embodiments, the concentration of the carbon source (e.g., renewable carbon source) is equivalent to between about 0.1% and about 20% glucose, such as between about 0.1% and about 10% glucose, between about 0.5% and about 10% glucose, between about 1% and about 5% glucose, or between about 1% and about 2% glucose.

In some embodiments, the carbon source comprises yeast extract or one or more components of yeast extract. In some embodiments, the concentration of yeast extract is at least or about 1 gram yeast extract per liter of culture broth (g/L, wherein the volume of culture broth includes the volume of cell culture medium and the volume of cells), such as at least or about 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, 150, 200, 300 or more g/L. In some embodiments, the concentration of yeast extract is between about 1 and about 300g/L, such as between about 1 and about 200g/L, between about 5 and about 200g/L or between about 5 and about 100g/L, or between about 5 and about 60 g/L. In some embodiments, the concentration includes the total amount of yeast extract added before and/or during culturing of the host cell. In some embodiments, the carbon source comprises yeast extract (or one or more components thereof) and another carbon source, such as glucose. In some embodiments, the ratio of yeast extract to another carbon source is about 1: 5, about 1: 10, or about 1: 20 (w/w).

Alternatively, the carbon source may be a carbon substrate such as carbon dioxide or methanol. Glycerol production from a carbon source (e.g., methanol, formaldehyde or formic acid) has been reported in methylotrophic yeasts (Yamada et al, agric. biol. chem., 53(2) 541-. These organisms can assimilate the monocarbon compounds from methanol to formic acid in the oxidized state and produce glycerol. The pathway of carbon assimilation can be via the ribulose monophosphate pathway, via the serine pathway or via the xylulose monophosphate pathway (Gottschalk, Bacterial Metabolism, 2 nd edition, Springer-Verlag: New York, 1986, which is incorporated herein by reference in its entirety, in particular with respect to the carbon source). The ribulose monophosphate pathway involves the condensation of formic acid with ribulose-5-phosphate to form a six-carbon sugar that becomes fructose and ultimately the three-carbon product glyceraldehyde-3-phosphate. Similarly, the serine pathway assimilates mono-carbon compounds into the glycolytic pathway by means of methylenetetrahydrofolate.

In addition to one and two carbon substrates, it is known that methylotrophic organisms also utilize numerous other carbon-containing compounds such as methylamine, glucosamine and various amino acids for metabolic activity. For example, methylotrophic yeasts are known to utilize methylamine-derived carbons to form trehalose or glycerol (Bellon et al, Microb. growth Cl Compd., [ int. Symp. ], 7 th edition, 415-32. editor: Murrell et al, Publisher: Intercept, Andover, UK, 1993, which is incorporated herein in its entirety by reference, particularly with respect to carbon sources). Similarly, various species of the genus Candida metabolize alanine or oleic acid (Sulter et al, Arch. Microbiol.153(5), 485-9, 1990, incorporated herein by reference in its entirety, particularly with respect to carbon sources).

In some embodiments, the cells are cultured in standard media containing physiological salts and nutrients (see, e.g., Pourquie, J. et al, Biochemistry and Genetics of cell Degradation editor: Aubert et al, Academic Press, pages 71-86, 1988; and Ilmen et al, appl. environ. Microbiol.63: 1298-1306, 1997, which are thus incorporated by reference, particularly with respect to the cell culture media). Exemplary growth media are common commercially prepared media such as Luria Bertani (LB) broth, Sabouraud Dextrose (SD) broth, or Yeast Medium (YM) broth. Other defined or synthetic growth media may also be used, and suitable media for growing a particular host cell are known to those skilled in the art of microbiology or fermentation science.

In addition to a suitable carbon source, the cell culture medium desirably contains suitable minerals, salts, cofactors, buffers, and other components known to those skilled in the art to be suitable for use in culture growth or to enhance isoprene production (see, e.g., WO 2004/033646 and references cited therein and WO 96/35796 and references cited therein, each of which is thus incorporated by reference in its entirety, particularly with respect to the cell culture medium and cell culture conditions). In some embodiments where the isoprene synthase nucleic acid, DXS nucleic acid, IDI nucleic acid, and/or MVA pathway nucleic acid is under the control of an inducible promoter, an inducing agent (e.g., a sugar, a metal salt, or an antimicrobial agent) is desirably added to the culture medium at a concentration effective to induce expression of the isoprene synthase, DXS, IDI, and/or MVA pathway polypeptide. In some embodiments, the cell culture medium has an antibiotic (e.g., kanamycin) corresponding to an antibiotic resistance nucleic acid (e.g., kanamycin resistance nucleic acid) on a vector having one or more DXS, IDI, or MVA pathway nucleic acids.

Exemplary production of isoprene

In some embodiments, the cells are cultured in a medium under conditions that allow production of isoprene from the cells. In some embodiments, the cells are cultured at greater than or about 1, 10, 25, 50, 100, 150, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1,000, 1,250, 1,500, 1,750, 2,000, 2,500, 3,000, 4,000, 5,000, or more nanomoles of isoprene per gram of cells based on wet weight of cells per hour (nanomoles/g) _wcmPer hour) to produce isoprene. In some embodiments, the amount of isoprene is from about 2 to about 5,000 nanomoles/g_wcmBetween/hour, e.g., from about 2 to about 100 nanomoles/g_wcmBetween about 100 and about 500 nanomoles/g per hour_wcmBetween about 150 and about 500 nanomoles/g per hour_wcmBetween about 500 and about 1,000 nanomoles/g per hour_wcmBetween about 1,000 and about 2,000 nanomoles/g_wcmPer hour or from about 2,000 to about 5,000 nanomoles/g_wcmBetween hours. Unit is nanomole/g_wcmThe amount of isoprene per hour can be measured as disclosed in U.S. patent No. 5,849,970, which is incorporated herein by reference in its entirety, particularly with respect to the measurement of isoprene production. For example, isoprene (see, e.g., Greenberg et al, Atmos. environ.27A: 2689-. Conversion of gas chromatography area units by means of a standard isoprene concentration calibration curve To nmol isoprene. In some embodiments, the method is performed by obtaining a of a cell culture sample₆₀₀The value and then being based on having a known A₆₀₀Wet weight calibration curve of cell culture of value this A₆₀₀Values are converted to grams of cells and the grams of cells based on wet weight of cells are calculated. In some embodiments, by assuming possession of A₆₀₀A1 liter culture broth (including cell culture medium and cells) with a value of 1 had a wet cell weight of 1 gram, and the grams of cells were estimated. This value is also divided by the number of hours, such as 3 hours, that the culture has been incubated.

In some embodiments, the cells are cultured in greater than or about 1, 10, 25, 50, 100, 150, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1,000, 1,250, 1,500, 1,750, 2,000, 2,500, 3,000, 4,000, 5,000, 10,000, 100,000, or more ng isoprene per gram of cells on a wet weight of cells per hour (ng/g)_wcmPer hour) to produce isoprene. In some embodiments, the amount of isoprene is from about 2 to about 5,000ng/g_wcmBetween hours, e.g., from about 2 to about 100ng/g_wcmBetween hours, about 100 to about 500ng/g_wcmBetween hours, about 500 to about 1,000ng/g_wcmBetween one hour, about 1,000 to about 2,000ng/g_wcmPer hour or from about 2,000 to about 5,000ng/g _wcmBetween hours. Can be measured by the unit nanomole/g discussed above_wcmIsoprene production per hour multiplied by 68.1 calculated in ng/g_wcmAmount of isoprene per hour (as described in equation 5 below).

In some embodiments, the cultured cells produce a cumulative titer (total) of isoprene at greater than or about 1, 10, 25, 50, 100, 150, 200, 250, 300, 400, 500, 600, 700, 800, 900, 1,000, 1,250, 1,500, 1,750, 2,000, 2,500, 3,000, 4,000, 5,000, 10,000, 50,000, 100,000, or more mg isoprene per L of culture fluid (mg/L, where the volume of culture fluid includes the volume of cells and the volume of cell culture medium). In some embodiments, the amount of isoprene is from about 2 to about 5,000mg/L_{Culture solution}E.g., from about 2 to about 100mg/L_{Culture solution}Between about 100 and about 500mg/L_{Culture solution}Between about 500 and about 1,000mg/L_{Culture solution}Between about 1,000 and about 2,000mg/L_{Culture solution}Or from about 2,000 to about 5,000mg/L_{Culture solution}In the meantime. Can be passed through the slave OD₆₀₀Cell cultures with a value of approximately 1.0 take 1mL samples, place the samples in 20mL vials, incubate for 30 minutes and then measure the amount of isoprene in the headspace and measure the specific productivity of isoprene in mg isoprene/L from the headspace of shake flasks or similar cultures. If OD is greater than the total ₆₀₀The value is not 1.0, then the magnitude can be determined by dividing by the OD₆₀₀Values normalized to OD₆₀₀The value is 1.0. The value of mg isoprene/L headspace can be converted to mg/L by multiplying by a factor 38_{Culture solution}OD of culture Medium/hr₆₀₀. The unit is mg/L_{Culture solution}hour/OD₆₀₀Can be multiplied by the number of hours and the OD₆₀₀Values were obtained to obtain cumulative titers in mg isoprene/L broth.

The amount of isoprene (e.g., in units of per L) can be analyzed by taking a sample of the fermentor off-gas_{Gas (es)}mg isoprene) and this value is multiplied by the rate of off-gas passage per liter of broth (e.g., at 1vvm (volume of air/volume of broth/minute), which is 60L per hour_{Gas (es)}) Measured in mg/L in the fermenter_{Culture solution}Instantaneous isoprene production rate per hour. Thus, 1mg/L_{Gas (es)}Corresponding to an exhaust gas level of 60mg/L at an air flow rate of 1vvm_{Culture solution}Instantaneous production rate per hour. According to the requirement, the unit is mg/L_{Culture solution}The value per hour can be divided by the OD₆₀₀Value to obtain unit of mg/L_{Culture solution}Specific rate per hour/OD. mg isoprene/L_{Gas (es)}The average value of (d) can be converted to total productivity (g isoprene per liter fermentation broth, mg/L) by multiplying this average off-gas isoprene concentration by the total amount of off-gas produced per liter fermentation broth during fermentation _{Culture solution}). Thus, the average exhaust gas isoprene concentration was 0.5mg/L over 10 hours at 1vvm_{Culture solution}Hour corresponds to 300mg of isoprene/L_{Cultivation method} _{Nutrient solution}OfThe product concentration.

In some embodiments, the cultured cells convert greater than or about 0.0015, 0.002, 0.005, 0.01, 0.02, 0.05, 0.1, 0.12, 0.14, 0.16, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.2, 1.4, or 1.6% of the carbon in the cell culture medium to isoprene. In some embodiments, the percentage of carbon converted to isoprene is between about 0.002 to about 1.6%, such as about 0.002 to about 0.005%, about 0.005 to about 0.01%, about 0.01 to about 0.05%, about 0.05 to about 0.15%, 0.15 to about 0.2%, about 0.2 to about 0.3%, about 0.3 to about 0.5%, about 0.5 to about 0.8%, about 0.8 to about 1.0%, or about 1.0 to about 1.6%. The percent carbon conversion to isoprene (also referred to as "% carbon yield") can be measured by the moles of carbon in the isoprene produced divided by the moles of carbon in the carbon source (e.g., moles of carbon in glucose and yeast extract fed and dosed in batches). This number is multiplied by 100% to give a percentage value (as shown in equation 1).

Equation 1

% carbon yield (moles of carbon in isoprene produced)/(moles of carbon in carbon source) 100

For this calculation, the yeast extract may be assumed to contain 50% w/w carbon.

Equation 2

% carbon yield ═ 0.042%

One skilled in the art can readily convert the rate of isoprene production or the amount of isoprene produced to any other units. An exemplary equation for the mutual scaling between units is listed below.

Units of isoprene production rate (sum of totals)Ratio of)

Equation 3

1g isoprene/L_{Culture solution}14.7 mmol/L isoprene/h_{Culture solution}Hour (total volume fraction).

Equation 4

1nmol isoprene/g_wcm1nmol isoprene/L/h_{Culture solution}hour/OD₆₀₀(the conversion assumes OD₆₀₀1 liter of culture broth with a value of 1 had a wet cell weight of 1 gram).

Equation 5

1nmol isoprene/g_wcm68.1ng isoprene/g/h_wcmHour (molecular weight of isoprene given)

Equation 6

1nmol isoprene/L_{Gas (es)}O₂90nmol isoprene/L/hr_{Culture solution}Hour (O at 90L/hour per L culture broth)₂At the velocity of flow)

Equation 7

1 μ g isoprene/L in the exhaust gas_{Gas (es)}Isoprene is 60L_{Gas (es)}Each L of_{Culture solution}60. mu.g of isoprene/L at a flow rate of (1vvm)_{Culture solution}Hour/hour

Titer unit (Total sum ratio)

Equation 8

1nmol isoprene/mg cellular protein 150nmol isoprene/L_{Culture solution}/OD₆₀₀(the conversion assumes OD₆₀₀1 liter of culture solution of value 1 has about 150mg of total cellular protein) (specific productivity).

Equation 9

1g isoprene/L_{Culture solution}14.7mmol of isoprene/L_{Culture solution}(Total Titer).

Equation 10 can be used to convert any unit, including the wet weight of the cells to the corresponding unit including the dry weight of the cells, as desired.

Equation 10

Dry cell weight (wet cell weight)/3.3

In some embodiments encompassed by the present invention, cells comprising a heterologous nucleic acid encoding an isoprene synthase polypeptide produce an amount of isoprene that is at least or about 2-fold, 3-fold, 5-fold, 10-fold, 25-fold, 50-fold, 100-fold, 150-fold, 200-fold, 400-fold, or more, the amount of isoprene produced from corresponding cells grown under substantially identical conditions that do not contain the heterologous nucleic acid encoding the isoprene synthase polypeptide.

In some embodiments encompassed by the present invention, cells comprising a heterologous nucleic acid encoding an isoprene synthase polypeptide and one or more heterologous nucleic acids encoding DXS, IDI, and/or MVA pathway polypeptides produce an amount of isoprene that is at least or about 2-fold, 3-fold, 5-fold, 10-fold, 25-fold, 50-fold, 100-fold, 150-fold, 200-fold, 400-fold, or more, the amount of pentadiene produced from a corresponding cell grown under substantially the same conditions without the heterologous nucleic acid.

Exemplary isoprene purification Process

In some embodiments, any of the methods described herein further comprise recovering isoprene. For example, isoprene produced using the compositions and methods of the present invention can be recovered using standard techniques such as stripping, fractionation, adsorption/desorption, pervaporation, thermal or vacuum desorption of isoprene from a solid phase or extraction of isoprene immobilized to or adsorbed on a solid phase with a solvent (see, e.g., U.S. patent nos. 4,703,007 and 4,570,029, each of which is hereby incorporated by reference in its entirety, particularly with respect to isoprene recovery and purification processes). In some embodiments, the recovery of isoprene involves isolating isoprene in liquid form (e.g., a neat solution of isoprene or a solution of isoprene in a solvent). The stripping process involves the removal of isoprene vapor from the fermentation off-gas stream in a continuous manner. This removal can be accomplished in several different ways, including, but not limited to, adsorption to a solid phase, partitioning into a liquid phase, or direct condensation. In some embodiments, the membrane enrichment of the thin isoprene vapor stream at the dew point of the isoprene vapor results in condensation of liquid isoprene.

The recovery of isoprene may involve one step or multiple steps. In some embodiments, the removal of isoprene vapor from the fermentation off-gas and the conversion of isoprene to the liquid phase are performed simultaneously. For example, isoprene may be condensed directly from the exhaust stream to form a liquid. In some embodiments, the removal of isoprene vapor from the fermentation off-gas stream and the conversion of isoprene to the liquid phase are performed sequentially. For example, isoprene may be adsorbed to a solid phase and subsequently extracted from the solid phase with a solvent.

In some embodiments, any of the methods described herein further comprise purifying the isoprene. For example, isoprene produced using the compositions and methods of the invention can be purified using standard techniques. Purification refers to a process by which isoprene is separated from one or more components present at the time of isoprene production. In some embodiments, the isoprene is obtained as a substantially pure liquid. Examples of purification methods include (i) distillation from a solution in a liquid extractant and (ii) chromatography. As used herein, "purified isoprene" means isoprene that is separated from one or more components present when isoprene is produced. In some embodiments, the isoprene is at least about 20% (by weight) and is free of other components present when isoprene is produced. In various embodiments, the isoprene has a purity of at least or about 25%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90%, 95%, or 99% by weight. Purity can be determined by any suitable method, for example by column chromatography, HPLC analysis or GC-MS analysis.

Crystal structure of isoprene synthase

The present invention also contemplates crystalline forms of plant isoprene synthase (e.g., poplar and kudzu) and variants thereof as described above and in the examples. In one embodiment, the invention includes any polypeptide having the crystal structure of poplar isoprene synthase as disclosed in tables 16-7.

Experiment of

The following examples are provided to illustrate and further illustrate certain preferred embodiments and aspects of the present invention and should not be construed as limiting the scope of the invention.

In the subsequent experimental disclosure, the following abbreviations are used: deg.C (degrees Celsius); rpm (revolutions per minute); h₂O (water); diH₂O (deionized water); AA and AA (amino acids); bp (base pair); kb (kilobase pair); kD (kilodalton); gm (gram); μ g and ug (micrograms); mg (milligrams); ng (nanogram); μ l and ul (microliters); ml (milliliters); mm (millimeters); qs (sufficient amount); nm (nanometers); μ m and um (micrometers); m (mole); mM (millimolar); μ M and uM (micromolar); pM (picomolar); u (unit); MW (molecular weight); sec (seconds); min (minutes); hr (hours); OD₆₀₀(optical density at 600 nm); BSA (bovine serum albumin); DMAPP (dimethylallyl diphosphate); DTT (dithiothreitol); EtOH (ethanol); IPTG (isopropyl- β -D-thiogalactopyranoside); isoprene (2-methyl-1, 3-butadiene); IspS (isoprene synthase); PAGE (polyacrylamide gel electrophoresis); PBS (phosphate buffered saline [150mM NaCl, 10mM sodium phosphate buffer, pH 7.2) ]) And SDS (sodium dodecyl sulfate).

The following abbreviations apply to the companies whose products or services have been mentioned in the experimental examples: agilent (Agilent Technologies, Santa Clara, Calif.); becton Coulter (Becton Coulter, inc., Fullerton, CA); Bio-Rad (Bio-Rad Laboratories, Hercules, Calif.); cayman Chemical (Cayman Chemical co., Ann Arbor, MI); CTC Analytics (CTC Analytics a.g., Zwingen, switzerland); EMS (Electron Microcopy Supply, Hatfield, Pa.); epicentre (Epicentre biotechnology, Madison, WI); integrated DNA Technologies (Integrated DNA Technologies, Coralville, IA); invitrogen (Invitrogen corp., Carlsbad, CA); molecular Dynamics (Molecular Dynamics, Sunnyvale, CA); novagen (Novagen, inc., Madison, WI); perkin Elmer (Perkin Elmer, Waltham, MA); roche (Roche Applied Science, indinopolis, IN); sigma (Sigma-Aldrich, st. louis, MO); stratagene (Stratagene Cloning Systems, La Jolla, Calif.); qiagen (Qiagen, inc., Valencia, CA); takara (Takara Bio USA, Madison, Wis.); thomson Instrument co., Oceanside, CA); v & P Scientific (V & P Scientific, Inc., San Diego, Calif.); and Zinsser (Zinsser North America, Northridge, CA).

Example 1

Cloning of kudzu isoprene synthase for expression in recombinant bacteria

In this example, a method for producing kudzu isoprene synthase (IspS) in E.coli is described. The protein sequence of the kudzu (kudzu) isoprene synthase gene (IspS) was obtained from GenBank (AAQ 84170). A gene for pueraria isoprene synthase optimized for e.coli codon usage was purchased from DNA2.0(Menlo Park, CA) and is shown in SEQ ID NO: 1 (fig. 1). The isoprene synthase gene was removed from the provided plasmid by restriction endonuclease digestion with BspLU11I/PstI, gel-purified and ligated into pTrcHis2B (Invitrogen) which had been digested with NcoI/PstI. The construct was designed such that the stop codon in the isoprene synthase gene was located 5' to the PstI site. Thus, the His tag was not linked to the isoprene synthase protein when the construct was expressed. The resulting plasmid pTrcKudzu was verified by sequencing.

The isoprene synthase gene was also cloned into pET16b (Novagen). In this case, the isoprene synthase gene was inserted into pET16b so that the recombinant isoprene synthase protein contained an N-terminal His tag. Using primer set pET-His-Kudzu-2F: 5' -CGTGAGATCA TATGTGTGCG ACCTCTTCTC AATTTAC (SEQ ID NO: 3) and pET-His-Kudzu-R: 5' -CGGTCGACGG ATCCCTGCAG TTAGACATAC ATCAGCTG (SEQ ID NO: 4), the isoprene synthase gene was amplified from pTrcKudzu by PCR. These primers add an NdeI site at the 5 'end of the gene and a BamHI site at the 3' end of the gene, respectively. Using the plasmid pTrcKudzu as described above as template DNA, HERCULASE DNA polymerase (Stratagene) was used according to the manufacturer's instructions and the primers were added at a concentration of 10 pM. PCR was performed in a total volume of 25. mu.l. The PCR product was digested with NdeI/BamH1 and cloned into pET16b digested with the same enzymes. The ligation mixture was transformed into E.coli Top10(Invitrogen) and the correct clones were selected by sequencing. The resulting plasmid, designated pETNHisKudzu, was subsequently transformed into BL21(λ DE3) pLysS (Novagen) cells for expression from the T7 promoter.

The kudzu isoprene synthase gene was also cloned into the low copy number plasmid pCL1920(Lerner and Inouye, Nucl Acids Res, 18: 4631, 1990). The pueraria isoprene synthase gene was amplified from pTrcKudzu described above using primers. The forward primer was added a HindIII site and an E.coli consensus RBS to the 5' end. The PstI cloning site is already present in pTrcKudzu just 3' of the stop codon, and thus, the reverse primer was constructed so that the final PCR product included this PstI site. The sequence of the primer is as follows: HindIII-rbs-Kudzu F: 5' -CATATGAAAG CTTGTATCGA TTAAATAAGG AGGAATAAAC C (SEQ ID NO: 5) and BamH 1-Kudzzu R: 5' -CGGTCGACGG ATCCCTGCAG TTAGACATAC ATCAGCTG (SEQ ID NO: 4). The PCR product was amplified using HERCULASE DNA polymerase (Stratagene) with primers at a concentration of 10pM and 1ng template DNA (pTrcKudzu). The amplification protocol included 30 cycles (95 ℃ for 1 min, 60 ℃ for 1 min, 72 ℃ for 2 min). The product was digested with HindIII and PstI and ligated into pCL1920 which had also been digested with HindIII and PstI. The ligation mixture was transformed into E.coli Top 10. Several transformants were verified by sequencing analysis. The resulting plasmid was designated pCL-lac-Kudzu.

To remove the beta-lactamase gene, pTrcKudzu was digested with BspHI, treated with Shrimp Alkaline Phosphatase (SAP), incubated at 65 ℃ for 10 minutes to heat-inactivate SAP, followed by end-filling by incubation with 2 units of Klenow fragment (New England BioLabs) and dNTP. The 5kb fragment was purified from the agarose gel and ligated to the Kan (R) gene. The Kan (R) gene was prepared by PCR from pCR-Blunt-II-TOPO (Invitrogen) using primers MCM22 and MCM23 and Taq DNA polymerase according to the manufacturer's instructions. The PCR fragment was digested with HindIII and PvuI and end-filled using Klenow fragment and dNTP. The ligation mixture was transformed into E.coli Top 10 chemically competent cells and transformants carrying the plasmid pTrcKudzu (kan) conferring kanamycin resistance were selected on Luria agar containing kanamycin (50. mu.g/ml). The sequence of the primer is as follows: MCM225 '-gatcaagcttAACCGGAATTGCCAGCTG (SEQ ID NO: 15) and MCM 235' -gatccgatcgTCAGAAGAACTCGTCAAGAAGGC (SEQ ID NO: 16).

Example 2

Cloning of poplar isoprene synthase for expression in recombinant bacteria

In this example, a method for producing poplar isoprene synthase (IspS) in E.coli was described. The protein sequence of poplar (Populus alba x Populus tremula) isoprene synthase (Schnitzler et al, Planta 222: 777-786, 2005) was obtained from GenBank (CAC 35696). One gene codon optimized for e.coli was purchased from DNA2.0 and is shown in SEQ ID NO: 6 (fig. 3). The isoprene synthase gene was removed from the provided plasmid (p9796-poplar) by restriction endonuclease digestion with BspLU11I/PstI, gel purified and ligated into pTrcHis2B which had been digested with NcoI/PstI. The construct was cloned such that the stop codon in the insert sequence precedes the PstI site, which resulted in a construct in which the His tag was not linked to the isoprene synthase protein. The resulting plasmid pTrcPoplar was verified by sequencing using commercially available primers hybridizing inside the vector sequence (forward and reverse) and the primer Poplar InSeq InSeq 5' GAGAAAATCG GTAAGGAACT GG (SEQ ID NO: 8).

Example 3

Isoprene production in recombinant bacteria

In this example, methods for producing and measuring isoprene in recombinant E.coli are described.

1. Determination of isoprene production

For shake flask cultures, 1 culture was transferred from the shake flask to a 20ml CTC headspace vial (Agilent vial catalog No. 51882753 and vial lid catalog No. 51882759). The cap was screwed and the vial was incubated at constant temperature with shaking at 250 rpm. After 30 minutes, the vial was removed from the incubator and analyzed as described below. In the case where isoprene production in the fermentor was determined, samples were taken from the off-gas of the fermentor and analyzed directly.

The analysis was performed using an Agilent 6890 GC/MS system coupled to a CTC analytical combiPAL autosampler operating in headspace mode. An Agilent HP-5MS GC/MS column (30 mx0.25mm; 0.25 μm membrane thickness) was used for analyte isolation. The injector was set to inject 500 μ L of headspace gas. The GC/MS method utilizes helium as a carrier gas at a flow rate of 1 ml/min. The injection port was maintained at 250 ℃ with a split ratio of 50: 1. During the analysis, the oven temperature was maintained at 37 ℃ for 2 minutes. The Agilent 5793N mass selective detector operates in Single Ion Monitoring (SIM) mode at m/z 67. The detector was turned off from 1.4 to 1.7 minutes to allow the permanent gas to elute. Under these conditions, isoprene (2-methyl-1, 3-butadiene) was observed to elute at 1.78 minutes. Calibration tables were used to quantify the absolute amount of isoprene and found to be linear from 1. mu.g/L to 200. mu.g/L. Using this method, the detection limit is estimated to be 50 to 100 ng/L.

Production of isoprene in Shake flasks

The vector described above was introduced into E.coli strain BL21(λ DE3) pLysS (Novagen) to produce strains BL21/ptrcKudzu, BL21/pCL-lac-Kudzu and BL 21/pETHIsKudzu. The strains were spread for isolation on LA (Luria agar) containing the appropriate antibiotic (50. mu.g/ml carbenicillin for BL21/ptrcKudzu and BL21/pETHIsKudzu or 50. mu.g/ml spectinomycin for BL 21/pCL-lac-Kudzu) and incubated overnight at 37 ℃. A single colony was inoculated into a 250ml baffled shake flask containing 20ml Luria Bertani medium (LB) and the appropriate antibiotic. The cultures were incubated at 20 ℃ overnight with shaking at 200 rpm. OD measurement of overnight cultures₆₀₀And the culture is diluted to contain the appropriate antibodyBiotin 30ml MAGICEDIA expression Medium (Invitrogen) to OD in 250ml baffled shake flasks₆₀₀About 0.05. The culture was incubated at 30 ℃ overnight with shaking at 200 rpm. When OD is reached₆₀₀Is about 0.5-0.8, 400. mu.M IPTG is added and the cells are incubated at 30 ℃ for a further 6 hours with shaking at 200 rpm. After 0, 2, 4 and 6 hours of induction with IPTG, 1ml aliquots of the cultures were collected and OD determined₆₀₀And the amount of isoprene produced was measured as described above.

III.14L production of isoprene from BL21/ptrcKudzu in fermentation

Large-scale production of isoprene from E.coli containing recombinant kudzu isoprene synthase genes was determined from fed-batch cultures. The formulation of fermentation medium (TM2) per liter of fermentation medium was as follows: k₂HPO₄ 13.6g，KH₂PO₄ 13.6g，MgSO₄*7H₂O2 g, citric acid monohydrate 2g, ferrous ammonium citrate 0.3g, (NH)₄)₂SO₄3.2g, yeast extract 5g, 1000 × modified trace metals solution 1 ml. All components are added together and dissolved in diH₂And (4) in O. The pH was adjusted to 6.8 with potassium hydroxide (KOH) and made up to volume. The final product was sterile filtered through a 0.22 μ M filter, but was not autoclaved. 1000 x formulation of modified trace metal solution as follows: citric acid H₂O 40g，MnSO₄*H₂O 30g，NaCl 10g，FeSO₄*7H₂O 1g，CoCl₂*6H₂O 1g，ZnSO₄*7H₂O 1g，CuSO₄*5H₂O 100mg，H₃BO₃ 100mg，NaMoO₄*2H₂O100 mg. Each component is dissolved in diH one time₂In O, the pH is adjusted to 3.0 with HCl/NaOH, then made up to volume and filter sterilized with a 0.22 μ M filter.

The experiment was performed in a 14L bioreactor to monitor the formation of isoprene from glucose at the desired fermentation, ph6.7 and temperature 34 ℃. Prepared from frozen soy peptone-yeast extract-glucose medium in 2 600ml flasksVials of inoculum of E.coli strain BL 21/ptrcKudzu. Growth to OD in the inoculum ₅₅₀After 0.6, the 2 600ml flasks were centrifuged and the contents resuspended in 70ml supernatant to transfer the cell pellet (70ml of OD 3.1 material) to the bioreactor. At various times after inoculation, samples were taken and the amount of isoprene produced was measured as described above.

Example 4

Selection of sites for improving plant isoprene synthase

Plant isoprene synthase is expected to be homologous to terpene synthase. The three-dimensional structures of two homologous terpene synthases have been determined from a borneol-based diphosphate synthase (pdb entry 1N1B) and a 5-epi-aristochene synthase (pdb entry 5 EAU). These enzymes have only 32% homology, but their tertiary structure is conserved. Furthermore, the structure of the intermediate complex with these two enzymes shows: the tertiary folding and specific interactions in the active center of these enzymes are highly conserved.

As shown in Table 4-1 below, kudzu isoprene synthase and poplar isoprene synthase have higher sequence identity than that of borneol diphosphate synthase and 5-epi-Malaristochene synthase.

TABLE 4-1. percent identity of various enzymes

	BDP-synthases	5 EA-synthases	Kudzuvine IspS
				Populus IspS	40.1	32.9	54.4
Kudzuvine IspS	40.7	33.8
				5ES synthase	31.9

A homology model for poplar isoprene synthase has been generated based on the bornyl diphosphate synthase (BDP-synthase) pdb entry 1N24 (about 40% sequence identity). This homology model seems reasonable based on the close similarity of 10 experimental models generated using the program MOE written and maintained by Chemical Computing Group, inc. This rationale is based on the conservation of common amino acid residues at sites found to be involved in catalysis in the BDP-synthase structure.

Comparison of the active sites from the BDP-synthase structure with the Yang IspS homology model indicates that the active sites involved in metal ion binding and phosphate recognition are conserved. In particular, Lys 272, Asp 309, Asp 313, Glu 387, Arg 450 and Asn 453 of poplar IspS were observed to overlap with equivalent residues in BDP-synthase. In this example, the amino acid residue positions of poplar IspS are from SEQ ID NO: 7. the localization of the intermediate of BDP-synthase was also compared to the poplar IspS homology model. Based on this comparison, similar binding regions and proximity directions required for isopentenyl diphosphate to bind and react with the poplar IspS enzyme can be identified.

A homology model for pueraria isoprene synthase has been generated based on the borneol-based diphosphate synthase pdb entry 1N24 with about 40% sequence identity. Comparison of the active site from the BDP-synthase structure with the geisps homology model shows that many of the active site residues involved in metal ion binding and phosphate recognition are conserved. In particular, Arg 269, Asp 306, Asp 310, Glu 384, Arg 450 and Asn 453 of ge IspS were observed to overlap with equivalent residues in BDP-synthase.

Comparing the active site residues identified in the homology model for poplar and kudzu IspS revealed: residues from one homology model are also fairly homologous to similar residues in another homology model, with only slight shifts in the relative position numbering of some residues. Based on homology models, sites in poplar and pueraria IspS were identified as candidates for mutagenesis to generate variant IspS enzymes with improved performance. Briefly, the IspS are selected for sites that may alter metal binding, diphosphate recognition, IPP strand binding and/or active site proximity interactions.

I. Diphosphate/metal binding sites

The side chains of amino acid residues in the poplar IspS near the metal and Diphosphate (DPP) binding side chains were identified. These residues include Phe 384, Tyr 402, Ala 406, Ser 409, Ala 460 and Asn 469. The inventors noted that Lys 272 was incorrect based on homology to other known poplar IspS sequences with an Arg at this position.

Substrate proximity Ring

The substrate of poplar IspS is located close to the loop in a region distinct from the BDP-synthase structure. In the BDP-synthase structure, residues form a segment that produces a cage. Without being limited by theory, the inventors contemplate that this segment will form a similar structure in the actual three-dimensional structure of the young IspS. Thus, residues in this loop (including residues 455-466) will be in positions that alter the activity of the poplar IspS enzyme. In the poplar IspS enzyme, residues 455-466 have the following sequence: LASASAEIARGET (SEQ ID NO: 9).

Isopentenyl binding sites

The complex of BDP-synthase and the reaction product bornyl diphosphate (pdb entry 1N24) was used to identify residues in the poplar model that could modulate substrate specificity and/or reaction rate (altering the rate of substrate and product entry and exit). These residues include Arg 274, Trp 281, Phe 302, Val 305, Ser 411, Gln 415, Phe 449, Ser 537, and Glu 540.

TABLE 4-2 candidate mutagenesis sites

Leu 416	Leu 413/1237-1239
		Leu 521	Met 523/1567-1569
Ser 525	Ser 527/1579-1581

Example 5

Mutations of non-conserved cysteines in kudzu isoprene synthase

A comparison of homology models of kudzu and poplar isoprene synthases (IspS) based on the crystal structure of bornyl diphosphate synthase is made with respect to the location of cysteine residues. Cysteine has the potential to form disulfide bonds and to stabilize structures. Non-conserved cysteines thought to affect solubility and/or activity were altered by site-directed mutagenesis. The amino acid sequence of the kudzu IspS used for modeling is shown in FIG. 2 (SEQ ID NO: 2). As shown in the homology model of fig. 5, there are 8 cysteines in ge IspS at positions 57,291, 343, 378, 421, 446, 451, and 529 (relative to the mature form of the protein). In contrast, the poplar IspS amino acid sequence has 5 cysteines as shown in the homology model of figure 6 with pueraria cysteine superimposed thereon. Several of the cysteines were clearly conserved between the poplar IspS and pueraria IspS sequences, suggesting that these positions are important in stabilizing structure, activity, and/or other protein functions. The remaining cysteines in pueraria lobata (non-conserved residues 57,291,421 and 446) were mutated to serines as described herein.

I. Mutagenesis

QUIKCHANGEThe multiple site directed mutagenesis kit (Stratagene) was used according to the manufacturer's instructions. The following primers were used for mutagenesis:

C57S-F 5’-CTGGAGGAAGAAGTTCGC TCC

ATGATCAACCGTGTAGAC(SEQ ID NO：10)；

C291S-F 5’-CGCCAGACCCGCAGTTTGGTGAA TCT

CGCAAAGCTGTTACTAAAATG(SEQ ID NO：11)；

C421S-F 5’-CGCCGTCTTACTTTTCCGTA TCC

CAGCAGCAGGAAGACATC(SEQ ID NO：12)；

C446S-F 5’-CATGGTCTGGTGCGTTCTAGC TCC

GTTATCTTCCGCCTGTGC (SEQ ID NO: 13); and

C421S-R 5’-GATGTCTTCCTGCTGCTG GGA

TACGGAAAAGTAAGACGGCG(SEQ ID NO：14)。

the plasmid pTrcKudzu (kan) described in example 1 was used as a template DNA. Primers C57S-F, C291S-F, C421S-F and C446-F (100pmol) were combined in a single reaction. Add template DNA (about 200 ng) and 0.5. mu.l Quik solution to the recommended volume of enzyme and buffer. PCR reactions were performed in an Eppendorf PCR instrument using a renaturation temperature of 55 ℃ and an extension time of 12 minutes for 30 cycles. Other parameters of the cycle are as indicated in the specification. The PCR mixture was treated with DpnI at 37 ℃ for 4 hours (2X 1. mu.l each for 2 hours) and then 5. mu.l of the reaction was transformed into E.coli Top10(Invitrogen) chemically competent cells and seeded on Luria agar containing kanamycin (50. mu.g/ml). After overnight incubation at 37 ℃, several colonies were picked and inoculated into 5ml Luria medium containing kanamycin (50. mu.g/ml). Plasmids were isolated using the QIAprep centrifuge microfabrication kit (Qiagen) and the IspS gene was sequenced in its entirety. A variety of individual mutations and combinations of mutations were generated as shown in Table 5-1 below.

TABLE 5-1 BL21 (Lambda DE3) cells transformed with the mutated pTrcKudzu plasmid ^*

Bacterial strains^*	C57S	C291S	C421S	C446S
					C1	+	+
C2		+		+
					C4	+	+		+
C6	+			+
					C11				+
C20			+
					C6-4	+		+	+

All variant plasmids were transformed into chemically competent BL21(λ DE3) cells (Novagen). In the second reaction, pTrcKudzu (kan) isolated from C6 and plasmid DNA were used as templates (QUIKCHANGE) in a single-site reaction using C421S-F and C421S-R primersSite-directed mutagenesis kit (Stratagene)). After confirmation by sequencing, two additional strains were obtained.

Cell growth and isoprene production

Cells were incubated overnight at 30 ℃ in 5ml tubes containing LB medium (supplemented with 50mg/L kanamycin) with stirring. These cultures were diluted into TM3 medium supplemented with 10g/L glucose and 50mg/L kanamycin. The culture volume was 25ml in 250ml baffled Bellco Delong flasks in which the cells were incubated at 30 ℃ with stirring (225 rpm). As shown, the samples were taken aseptically for A₆₀₀Optical density measurements of (a). The results are shown in Table 7. Culture in 3Induced with 200 μ M IPTG for 33 hours and allowed to continue growth until harvest at 7.8 hours. The cultures were centrifuged at 10,000Xg for 10 min, the supernatant decanted and the cell pellet frozen at-80 ℃ overnight.

The frozen cell pellet was thawed and resuspended in 2ml PEB (50mM Tris-HCl, pH 8.0, 20mM MgCl) ₂2mM dithiothreitol and 50% [ v/v ]]Glycerol). Cells were lysed by french press disruption in a single pass at 20,000 psi. The lysate was centrifuged at 10,000Xg for 15 minutes. The supernatant was decanted and the pellet was resuspended in 2ml of PEB. The pellet and supernatant were analyzed by SDS-PAGE run under reducing conditions in MES buffer, 4-12% NuPage gel (Invitrogen). The molecular weight standard was SeeBlue2 (Invitrogen). The results are shown in table 8. The IspS protein concentration was estimated using the BCA assay (Pierce) using BSA as a standard (table 5-2).

Assays for isoprene synthase activity and solubility

Briefly, the activity of the supernatant was measured by reaction with DMAPP and the isoprene evolved was quantified by GC/MS.

Headspace assay. 200 μ l samples of the desired culture were inoculated into 2ml CTC headspace vials (Agilent vial catalog No. 51882753 and bottle lid catalog No. 51882759). The cap was screwed and the vial was incubated at 37 ℃ with shaking at 250 rpm. After 30 minutes, the vial was removed from the incubator and rapidly cooled with room temperature tap water. Vials were mounted into CombiPal headspace autosamplers for GC-MS analysis. The analysis was performed using an Agilent 6890 GC/MS system coupled to a CTC analytical combiPAL autosampler operating in headspace mode. An Agilent HP-5MS GC/MS column (30 mx0.25mm; 0.25 μm membrane thickness) was used for analyte isolation. The injector was set to inject 500 μ L of headspace gas. The GC/MS method utilizes helium as a carrier gas at a flow rate of 1 ml/min. The injection port was maintained at 250 ℃ with a split ratio of 50: 1. During the analysis, the oven temperature was maintained at 37 ℃ for 2 minutes. The Agilent 5793N mass selective detector operates in Single Ion Monitoring (SIM) mode at m/z 67. The detector was turned off from 1.4 to 1.7 minutes to allow the permanent gas to elute. Under these conditions, isoprene (2-methyl-1, 3-butadiene) was observed to elute at 1.78 minutes. Calibration tables were used to quantify the absolute amount of isoprene and found to be linear from 1. mu.g/L to 200. mu.g/L. Using this method, the detection limit was estimated to be 50-100 ng/L.

DMAPP assay. Add a 95 μ Ι aliquot of the supernatant fraction from the centrifuged french press cell lysate to the pre-empty vial. A 5 μ L aliquot of 8mM DMAPP in 100mM potassium phosphate buffer, pH 8.2 was added, the vial was sealed and allowed to incubate for 30 minutes at room temperature. The amount of isoprene produced was measured by GC/MS as described above and reported in Table 5-2.

TABLE 5-2 isoprene synthase Activity from crude cysteine mutant extracts

The values shown in Table 5-2 are the average of the responses with two different concentrations of extract. All proteins containing any cysteine mutation resulted in a severe impairment of the enzymatic activity and a significant reduction of the soluble protein, as indicated by a relative increase in the proportion of protein in the insoluble (precipitate) fraction.

Example 6

Mutations of residues in poplar isoprene synthase

The amino acid sequences of kudzu isoprene synthase and poplar isoprene synthase were aligned with other synthases using Vector Nti (Invitrogen). The aligned sequences include: lotus corniculatus (Lotus corniculatus) beta-ocimene synthase (AAT 86042); medicago truncatula (Medfigo trunculata) putative terpene synthases (AAV 36465); grape (Vitis vinifera) putative protein (can 65805); grape hypothetical protein (CAN 62729); quercus ilex (Quercus ilex) pinene synthase (CAK 55186); pueraria montana (kudzu) IspS (AAQ 84170); eucalyptus globulus (Eucalyptus globulus) monoterpene synthase (BAF 02832); populus nigra (Populus nigra forturnati) IspS (CAL 69918); populus tremuloides (Populus tremuloides Sharkey) IspS (AAQ 16588); populus alba IspS (BAD98243) and Populus alba x Populus tremula Zimmer IspS (CAC 35696). Sequences from the populus alba x populus tremula (CAC35696) database show different amino acids at positions 272 and 497, which are otherwise highly conserved. Position 453 was additionally identified as a third candidate for mutagenesis based on analysis of the homology model of the poplar IspS.

I. Mutagenesis

Using QUIKCHANGE according to manufacturer's instructionsMulti-site directed mutagenesis kit (Stratagene) to mutate: K272R; C497W; and N453D were introduced individually and in combination into the Populus alba x Populus tremula IspS sequence (SEQ ID NO: 7). The following primers were used for mutagenesis:

poplar K272R 5' -ccaaactgcacttcg ctcgtgaccgcctgattgag (SEQ ID NO: 17);

populus 453D 5' -atctttcgcctgtgcgacgacctggcaagc (SEQ ID NO: 18); and

populus C497W 5' -tgaatctgatcgacgaaacctggaagaaaatgaacaaagaaaaac (SEQ ID NO: 19).

The following primer, PoInSeq, 5' -gagaaaatcggtaaggaactgg (SEQ ID NO: 8), was used for sequencing.

Mutagenesis was performed according to the manufacturer's instructions, adding all three mutagenic primers to a single reaction mixture (100ng of each primer), with pTrcPoplar as template DNA (100 ng). Add 0.5 μ l Quik solution to assist the mutagenesis reaction. The recommended PCR cycle is performed at 55 ℃ renaturation temperature and 12 min extension time. Other parameters are as indicated in the specification. The PCR mixture was digested with DpnI at 37 ℃ for 4 hours (1. mu.l. times.2 hours each) and then 5. mu.l of the reaction was transformed into E.coli Top10(Invitrogen) chemically competent cells. Several colonies were selected and grown in 5ml Luria Broth (LB) containing carbenicillin (50. mu.g/ml). Plasmids were isolated using a Qiagen QIAprep centrifuge miniprep kit and sent for sequencing using the forward and reverse primers hybridized to the vector and the PopuleInSeq primer.

The resulting variant of ptrcpoptar was obtained: ptrcpoptar K272R; pTrcPoplan K272R/N453D; pTrcPoplan K272R/N453D/C497W; and pTrcPopla 272R/497W. These plasmids were transformed into BL21(λ DE3) pLysS chemically competent cells (Novagen) for analysis. The variants were analyzed for headspace activity (isoprene production from intact cells), solubility, and specific activity.

Cell growth and isoprene production

The variant (parent Poplar strain) and the strain containing pTrcKudzu were incubated overnight at 37 ℃ in 5ml Luria Bertani medium containing carbenicillin (50. mu.g/ml-Poplar strain) or kanamycin (50. mu.g/ml-Kudzu strain). These cultures were diluted to an OD of 0.05 in TM3 medium supplemented with 10g/L glucose and 50. mu.g/ml carbenicillin ((Popla mutant and wild type) or 50mg/L kanamycin (BL21/pTrcKudzu)₆₀₀. The formulation of the TM3 medium is as follows: k₂HPO₄(13.6g/l)，KH₂PO₄(13.6g/l)，MgSO₄*7H₂O (2g/L), citric acid monohydrate (2g/L), ammonium ferrous citrate (0.3g/L), (NH)₄)₂SO₄(3.2g/L), yeast extract (0.2g/L), 1ml 1000X trace metal solution, pH adjusted to 6.8 with ammonium hydroxide, sterile diH₂Make up to volume and filter sterilized with a 0.22 micron filter. The formulation of 1000 x trace metal solution is as follows: citric acid H ₂O(40g/L)，MnSO₄*H₂O(30g/L)，NaCl(10g/L)，FeSO₄*7H₂O(1g/L)，CoCl₂*6H₂O(1g/L)，ZnSO₄*7H₂O(1g/L)，CuSO₄*5H₂O(100mg/L)，H₃BO₃(100mg/L)，NaMoO₄*2H₂O (100 mg/L). Each component is dissolved in diH one time₂In O, the pH is adjusted to 3.0 with HCl/NaOH and made up toVolume, and filter sterilized with a 0.22 micron filter.

The diluted culture volume was 25ml in a 250ml baffled Bellco Delong flask and incubated at 30 ℃ with stirring (225 rpm). As shown, the samples were taken aseptically for A₆₀₀Optical density measurements of (a). Two sets of cultures were set up: one induced with 0.2mM IPTG and one kept uninduced. After 3 hours of growth at 30 ℃ with shaking at 200 rpm (OD)₆₀₀About 0.5), one set of cultures was induced with 0.2mM IPTG and incubated at 30 ℃ for a further 3 hours with shaking at 200 rpm; the uninduced group was incubated for the same amount of time. OD of all cultures was determined before induction time (3 hours after inoculation) and at the time isoprene was measured in the headspace assay (3 hours after induction, 6 hours of total growth)₆₀₀. The cell culture was centrifuged at 7000Xg for 15 minutes in a Sorvall ultracentrifuge to pellet the cells. The supernatant was removed and the cell pellet was frozen for in vitro assay of isoprene synthase activity. The results of the growth and headspace assays are shown in the table below.

TABLE 6-1 growth of E.coli strains expressing the PosIspS variants

(OD600 value)

TABLE 6-2 isoprene production (. mu.g/L) by E.coli strains expressing the Young IspS variants

Unexpectedly, the strain expressing geisps exhibited any measurable isoprene production. This was unexpected because the kinetic characteristics of the poplar enzyme were reported in the literature to be superior to those of the kudzu enzyme. In particular, the prior art describes recombinant kudzu IsSpecific Activity of pS (U/mg) and K_m(. mu.M) are 0.075 and 7,700, respectively, the specific activity (U/mg) and K of the natural Populus IspS_m(. mu.M) was 0.5 and 8,000, respectively, and the specific activities (U/mg) and K of the recombinant Populus IspS_m(. mu.M) are 0.16 and 9,000(Silver and Fall, J Biol Chem, 270: 13010. sup. 1316, 1995; Miller et al, Planta, 213: 483. sup. 487, 2001; and Sharkey et al, Plant Physiology, 137: 700. sup. 712, 2005), respectively). Published K for these three enzymes_mThe values were all quite high and overlapped with each other, but the specific activity of kudzu isoprene synthase was significantly inferior to that of the other two isoprene synthases.

Assays for isoprene synthase activity and solubility

By using the DMAPP assay, the activity of isoprene synthase can be measured directly, since DMAPP is a direct substrate for this enzyme. Cell pellets of the parent and mutant strains of Populus and wild type Kudzuvine strain were thawed and resuspended in 2ml of PEB (50mM Tris-HCl, pH 8.0, 20mM MgCl) ₂2mM dithiothreitol and 50% [ v/v ]]Glycerol). Cells were lysed by french press disruption in a single pass at 20,000 psi. The lysate (1ml) was then centrifuged at 20,000 rpm in a microfuge tube for 20 minutes at 4 ℃. The supernatant was removed and the pellet resuspended in 1ml of PEB. Supernatant and pellet samples were analyzed by SDS-PAGE and DMAPP assays, while total protein content was determined by BCA.

TABLE 6-3 DMAPP assay for isoprene production in supernatants from centrifuged cell lysates

Yields were normalized to the supernatant protein of total cell lysates.

TABLE 6-4 DMAPP assay of isoprene production from pellet of centrifuged cell lysate

Yields were normalized to the pellet protein of total cell lysate.

The poplar variant K272R/C497W showed a 1.8 fold increase in activity compared to wild type in the supernatant fraction of the induced culture. Similarly, the poplar variants K272R and K272R/C497W showed 5.2-fold and 3.4-fold increases in activity compared to wild type in the supernatant fraction of the uninduced culture. In addition, the poplar variant K272R showed a 2-fold increase in activity compared to wild type in the pellet of the induced culture. However, the most surprising result was that Pueraria IspS was more active (185-fold) than the Populus IspS used herein. In the above table, H2 is the name of the clone designated pTrcPopla K272R/C497W H2.

Example 7

Subcloning of kudzu isoprene synthase

In this example, a method used in constructing pueraria isoprene synthase (IspS) SEL is described. An expression vector for constructing a Site Evaluation Library (SEL) was generated, and the pueraria isoprene synthase gene was subcloned from the pcr2.1 vector (Invitrogen) into the pET24d vector (Novagen). The kudzu IspS gene was amplified from pTrcKudzu template DNA using primers MCM 505 '-GATCATGCAT TCGCCCTTAG GAGGTAAAAA AACATGTGTG CGACCTCTTC TCAATTTACT (SEQ ID NO: 20) and MCM 535' -CGGTCGACGG ATCCCTGCAG TTAGACATAC ATCAGCTG (SEQ ID NO: 21). PCR reaction was performed using Taq DNA polymerase (Invitrogen), and the resulting PCR product was cloned into pCR2.1-TOPO TA cloning vector (Invitrogen) and transformed into E.coli Top10 chemically competent cells (Invitrogen). The transformants were inoculated on LB agar containing carbenicillin (50. mu.g/ml) and incubated overnight at 37 ℃. A5 ml LB culture containing 50. mu.g/ml carbenicillin was inoculated with a single transformant and incubated overnight at 37 ℃. The 5 colonies were screened for the correct insert by sequencing the plasmid DNA isolated from 1ml liquid culture (Luria Broth) and purified using the QIAprep centrifugal miniprep kit (Qiagen). The resulting plasmid, designated MCM93, contained the ge IspS coding sequence in the pcr2.1 backbone (fig. 9). The sequence of MCM93 (SEQ ID NO: 22) is shown in FIG. 10.

The kudzu coding sequence was removed by restriction endonuclease digestion with PciI and BamH1(Roche) and gel purified using QIA Rapid gel extraction kit (Qiagen). pET24d vector DNA was digested with NcoI and BamHI (Roche), treated with shrimp alkaline phosphatase (Roche) and purified using the QIAprep centrifuge microfabrication kit (Qiagen). Using a Rapid DNA ligation kit (Roche), the Pueraria IspS fragment was ligated to NcoI/BamH 1-digested pET24d in a 5: 1 fragment-to-vector ratio in a total volume of 20. mu.l. A portion of the ligation mixture (5. mu.l) was transformed into E.coli Top 10 chemocompetent cells and plated on L agar containing kanamycin (50. mu.g/ml). The correct transformants were confirmed by sequencing and transformed into chemically competent BL21(λ DE3) pLysS cells (Novagen). After overnight growth on L agar containing kanamycin (50. mu.g/ml) at 37 ℃ single colonies were selected. A map of the resulting plasmid, designated pET24D-Kudzu, is shown in FIG. 11. The sequence of pET24D-Kudzu is shown in FIG. 12 (SEQ ID NO: 23). IspS activity was confirmed using the headspace assay as described in example 5.

Example 8

Construction of isoprene synthase Site Evaluation Library (SEL)

To improve the kinetic parameters of plant IspS, SELs were prepared at sites selected from a homology model for both the ge IspS enzyme and the poplar IspS enzyme. Although engineering at the indicated sites was predicted from this homology model to improve both enzymes, in this embodiment, ge SEL was described. The Pueraria IspS target surface sites include, but are not limited to: 26L, 30E, 31F, 33Q, 35L, 36E, 37N, 39L, 40K, 41V, 43K, 44L, 61R, 62V, 63D, 65Q, 87K, 94E, 95N, 99L, 100D, 105N, 137K, 138E, 143G, 144E, 182N, 184L, 185K, 187G, 189N, 190T, 225P, 226H, 247K, 257T, 258E, 259M, 266D, 334N, 353D, 357S, 358I, 361E, 389N, 392I, 393I, 398K, 401E, 421C, Q423, 424Q, 425E, 426D, 430H, 432L, 433R, 434S, 437D, 443R, 462L, 463E, 476H, 476N, 479D, 485Q, 508D, 532P, 515A, 513Q 533, 533Y, 433R, 537, 539G, 543P, 478 a, 478G, and 478P. Active site positions of Pueraria IspS order include, but are not limited to: 24P, 25N, 309Y, 310D, 377L, 381F, 384E, 399Y, 402N, 403A, 406S, 407S, 409G, 411A, 413L, 449F, 456A, 457T, 458S, 459A, 460A, 461E, 462L, 463E, 464R, 465G, 466E, 467T, 468T, 469N, 523M, 527S, and 531Y. Additional active site positions of geisps order include, but are not limited to; 20A, 21N, 22Y, 23Q, 271R, 278W, 299F, 302V and 408S. Each library SEL contains clones that include up to 20 different variants. For example, the pueraria isoprene synthase SEL 531 contains a variant in which the DNA triplet encoding tyrosine at position 531 of the mature pueraria enzyme is replaced by another DNA triplet encoding alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, proline, glutamine, arginine, serine, threonine, valine, or tryptophan. In short, a DNA triplet at a specific position in the DNA coding strand of mature IspS was replaced. The mutated IspS nucleic acid is then ligated into a suitable expression vector and used to transform a suitable host cell.

Site evaluation libraries were generated by either ordering synthetic constructs (e.g., DNA2.0) or by ordering primers with "nns" sequences replacing the codon to be mutated. The primers are then used to mutate the gene to generate SEL at the indicated sites using a commercially available mutagenesis kit (e.g., Stratagene) as already described (e.g., WO0507682a 2). Mutated codons were identified by sequencing analysis. Site libraries were arrayed in 96-well master plates and frozen for future use. Cultures were grown from this master plate and prepared for screening.

The desired end product is an IspS enzyme that functions optimally in a host that is metabolically engineered to maximize carbon flow through the IspS. For this purpose, several screening stages are used to ensure that the correct parameters are processed. Exemplary screening methods include, but are not limited to: expression, DMAPP feed method for HG production, mini-reactor method, protein assay, and headspace assay. Expression screening method: the following is an example of a method for analyzing the expression level of a protein. Soluble and insoluble fractions of cell lysate (obtained from lysed cell culture) were prepared by centrifugation. The resulting supernatant and pellet were analyzed by SDS-PAGE. The supernatant and the pellet were analyzed by densitometry for the presence of protein, and the percentage of soluble protein was determined.

In an exemplary embodiment, a pueraria locus evaluation library was constructed in the pET24D expression vector. pET24D-Kudzu vector containing the gene for Kudzu isoprene synthase served as template DNA.

Materials:

pET24D-Kudzu vector (about 50 ng/. mu.l)

Kudzuvine IS site-directed mutagenesis primer (Integrated DNA Technologies)

QUIKCHANGEMulti-site directed mutagenesis kit (Stratagene)

MJ Research PTC-200 Peltier thermal cycler (Bio-Rad Laboratories)

One Shot TOP10 competent cells (Invitrogen)

QIAprep centrifugal miniprep kit (Qiagen)

BL21(λ DE3) pLysS competent cells (Invitrogen)

Luria Broth (LB) agar plate

Method

The mutagenesis method is based on a codon-specific mutagenesis approach, wherein all possible mutations are generated in a particular DNA triplet using a single forward primer of 25 to 45 nucleotides in length comprising the designed particular triplet DNA sequence NNS (N-A, C, T or G; and S-C or G), wherein said NNS corresponds to the sequence of the codon to be mutated. This approach resulted in random incorporation of nucleotides at the specific pET24D-Kudzu destination codon. Table 8-1 lists the oligonucleotide primers used for mutagenesis, the numbers in the primer names corresponding to the codon positions in the mature kudzu isoprene synthase sequence. All oligonucleotide primers were synthesized on a 100 nanomolar scale (Integrated DNA Technologies) and purified by PAGE.

TABLE 8-1. Kudzuvine IspS codon-specific mutant primers

Primer sequences having the name SEQ ID

IS_A20 NO：24 CATAATTCCCGTCGTTCCNNSAACTATCAGCCAAACCTG

IS_N21 NO：25 CATAATTCCCGTCGTTCCGCANNSTATCAGCCAAACCTGTG

IS_Y22 NO：26 CCCGTCGTTCCGCAAACNNSCAGCCAAACCTGTGGAATTTC

IS_Q23 NO：27 GTCGTTCCGCAAACTATNNSCCAAACCTGTGGAATTTC

IS_R271 NO：28 CTGGATTTTGTACGCGACNNSCTGATGGAAGTTTATTTC

IS_W278 NO：29 CTGATGGAAGTTTATTTCNNSGCACTGGGTATGGCGCC

IS_F299 NO：30 CAAAGCTGTTACTAAAATGNNSGGTCTGGTGACGATCATC

IS_V302 NO：31 CTAAAATGTTTGGTCTGNNSACGATCATCGATGACGTG

IS_S408 NO：32 GAAAACGCCAGCGTTTCCTCCNNSGGTGTAGCGCTGCTGGC

PCR reactions were performed in 0.5ml thin-walled PCR tubes according to QUIKCHANGEThe manufacturer's protocol for the multiple site directed mutagenesis kit (Stratagene) was set up: 1. mu.l of pET24 Kudzu vector (50 ng/. mu.l); 1 μ l of a Pueraria IS site-directed forward mutagenesis primer (10 μ M); 2.5. mu.l of 10 XQUIKCHANGEA multiplex reaction buffer; mu.l dNTP mix, 1. mu.l QUIKCHANGEMultiple enzyme blend (2.5U/. mu.l); and 18.5. mu.l of autoclaved distilled water to provide 25. mu.l of total reaction mixture. pET24 Kudzu SEL was amplified using the following conditions: 95 ℃, 1 minute (only 1 st cycle), followed by 95 ℃ for 1 minute, 55 ℃ for 1 minute, 65 ℃ for 12 minutes and repeat the cycle 29 times. Subsequently, the reaction mixture was subjected to DpnI digestion (QUIKCHANGE) by adding 1.5. mu.l of DpnI restriction enzyme to each tube and incubating at 37 ℃ for 2 hours to digest the parent pET24D-Kudzu vectorMultiple site-directed mutagenesis kit supply). The DpnI-treated PCR reaction was then transformed into One Shot TOP10 competent cells (Invitrogen), seeded on LB agar plates containing 50. mu.g/ml kanamycin, and incubated overnight at 37 ℃. The next day, 96 random colonies were picked and sequenced to identify a minimum of 15 of the possible 19 amino acid variants. Once site-directed variants were identified, each variant clone was then inoculated in 5ml LB + 50. mu.g/ml kanamycin and grown overnight at 37 ℃ with shaking (250 rpm). The following day, plasmid DNA was purified using the QIAprep centrifuge microfabrication kit (Qiagen). Variant of Then, the cells were transformed into One Shot BL21 (. lamda.DE 3) pLysS competent cells (Invitrogen) for protein expression screening, inoculated on LB agar plates containing 50. mu.g/ml kanamycin and 30. mu.g/ml chloramphenicol, and incubated overnight at 37 ℃.

An alternative method for the production of pET24D-Kudzu SEL in pLysS cells of E.coli BL21(λ DE3) was also successfully used. TOP10 competent cell transformants obtained from the DpnI-treated PCR reactions described above were harvested by applying 3ml of LB medium to the TOP of the agar and resuspending the cells by scraping with a sterile plate spreader. 3ml pooled resuspended cells were then used to inoculate 25ml shake flasks containing LB + 50. mu.g/ml kanamycin. The pooled cultures were then incubated overnight at 37 ℃ with shaking (250 rpm). The following day, plasmid DNA was purified from the pooled cultures using the QIAprep centrifugal miniprep kit (Qiagen). The pooled plasmid DNA was subsequently transformed into One Shot BL21(λ DE3) pLysS competent cells for protein expression screening as described above.

To prepare master plates, the correct constructs were arrayed in quadruplicate in 96-well plates. One colony with the correct sequence was used to inoculate 4 wells and the plate was incubated in LB containing 50. mu.g/ml kanamycin at 37 ℃ for several hours to overnight with shaking (200 rpm). Sterile glycerol was added to the culture to a final concentration of 15% (for a final total volume of 150-. The plates were then sealed using BREATHEE-EASIER (EMS catalog number 70536-20) membranes and stored at-80 ℃.

Example 9

Production and purification of isoprene synthase inclusion bodies

Upon overexpression of pueraria isoprene synthase in strain BL21(λ DE3) in the presence of chaperonin GroELS, inclusion bodies containing the enzyme were formed. Briefly, pETNHisKudzu (U.S. application No. 61/013,574, incorporated herein by reference) was subcloned into pGro7(Takara catalog No. 3340) according to the manufacturer's instructions. 500mL of culture was grown essentially as described (Whittington et al, Proc Natl Acad Sci USA, 99: 15375-15380, 2002). Despite the presence of chaperonin and low temperature culture, this culture produces mainly inclusion bodies and only low levels of soluble active protein. The inclusion bodies were harvested using the IFOLD protein refolding system (Novagen catalog No. 71552-3) according to the manufacturer's instructions. This method results in high yields (> 50mg) of recombinant kudzu isoprene synthase. The purity of the inclusion bodies is shown in fig. 13. This preparation was used to generate rabbit polyclonal anti-isoprene synthase antiserum (Invitrogen).

Example 10

High throughput biochemical screening of isoprene synthase variants

This example describes a high throughput method for determining isoprene synthase activity. As described above in example 8, a library of BL21(λ DE3) pLysS E.coli host cells capable of expressing isoprene synthase variants was arrayed in 96-well plates and stored frozen at-80 ℃ as a 15% glycerol stock. To analyze plates with up to 96 variants, 96-pin MULTI-BLOT floating pin tool (floating pin tool) (V) &P Scientific catalog No. VP 408AF) A photocopy impression of the master plate of the glycerol stock was made on Luria broth agar containing the appropriate antibiotic (e.g., 30. mu.g/mL chloramphenicol, 50. mu.g/mL kanamycin). The replica plates were incubated overnight at 30 ℃ to allow the growth of bacterial plaques. Using the same floating needle replicator, a plate 96 square deep well plate containing 250. mu.L of TM3 medium supplemented with 0.08% Biospringer yeast extract and 1% glucose plus antibiotic (30. mu.g/mL chloramphenicol, 50. mu.g/mL kanamycin) was inoculated from the agar and incubated overnight at 30 ℃. The formulation of the TM3 medium is as follows: k₂HPO₄(13.6g/l)，KH₂PO₄(13.6g/l)，MgSO₄*7H₂O (2g/L), citric acid monohydrate (2g/L), ammonium ferrous citrate (0.3g/L), (NH)₄)₂SO₄(3.2g/L), yeast extract (0.2g/L), 1ml of 1000 Xmicroelement solution, pH adjusted to 6.8 with ammonium hydroxide, sterile diH₂Make up to volume and filter sterilized with a 0.22 micron filter. 1000 x solution of trace elementsThe formula is as follows: citric acid H₂O(40g/L)，MnSO₄*H₂O(30g/L)，NaCl(10g/L)，FeSO₄*7H₂O(1g/L)，CoCl₂*6H₂O(1g/L)，ZnSO₄*7H₂O(1g/L)，CuSO₄*5H₂O(100mg/L)，H₃BO₃(100mg/L)，NaMoO₄*2H₂O (100 mg/L). Each component is dissolved in diH one time₂In O, the pH was adjusted to 3.0 with HCl/NaOH, appropriated to volume, and filter sterilized with a 0.22 micron filter. The overnight cultures were diluted to an OD of 0.05 with the same medium ₆₀₀And incubated in another 96 square deep well plate (Thomson Instrument, Cat. No. 951652C) containing 600. mu.L of dilution per well. The dilutions were incubated at 30 ℃ with shaking to an OD of 0.8₆₀₀And subsequently induced with IPTG added to a concentration of 400 μ M. Plates were incubated for 5 hours and OD determined₆₀₀For quality control and normalization.

A volume of 400 μ L of the culture was transferred to a new 96 well plate (Perkin Elmer, Cat. No. 6008290) and cells were harvested by centrifugation at 2500 Xg in a Beckman Coulter Allegra 6R centrifuge. The pellet was resuspended in 200. mu.L of hypotonic buffer (5mM MgCL)₂5mM Tris HCl, 5mM DTT pH 8.0) and plates were frozen at-80 ℃ for a minimum time of 60 minutes. Assay buffer (57mM Tris HCl, 19mM MgCl) was assayed by thawing the plates and adding 32. mu.L of isoprene synthase DMAPP₂74. mu.g/ml DNase I (Sigma catalog number DN-25), 2.63X 10⁵U/ml READYLYSE lysozyme solution (Epicentre catalog number R1802M) and 5mg/ml molecular biology grade BSA). The plates were incubated at 25 ℃ for 30 minutes with shaking and then placed on ice. For isoprene production, an 80 μ L aliquot of lysate was transferred to a 96-deep well glass plate (Zinsser catalog No. 3600600) and 100mM KHPO was added ₄20 μ L of 10mM DMAPP solution at pH 8.2 (Cayman Chemical catalog number 63180). The plates were sealed with aluminum plate sealer (Beckman Coultor catalog No. 538619) and incubated for 60 minutes at 30 ℃ with shaking. The enzymatic reaction was terminated by heating the glass pad (70 ℃ for 5 minutes). Quantitatively as described in example 5The headspace of each well was analyzed.

To determine protein concentration, 5 μ L or more of the lysate was electrophoresed on a preformed gel (Invitrogen catalog No. NP0301BOX) for western blot analysis, followed by transfer to nitrocellulose membrane (Invitrogen catalog No. LC 2000). The primary antibody used was the anti-isoprene synthase antibody of example 9. After binding of the primary antibody, the Alexa Fluor 488-labeled secondary antibody was developed (Invitrogen catalog number A-11008) to allow quantitative signal determination. Western blot method was performed as described by Invitrogen. The fluorescence signal was recorded with a Molecular Dynamics STORM instrument set with a blue filter and quantitatively analyzed with the Molecular Dynamics IMAGEQUANT image analysis software package. From the amount of isoprene produced and A of the induced culture₆₀₀Or calculating the specific activity of the library member from the ratio of the concentrations of isoprene synthase proteins determined by western blotting. Isoprene synthase protein standards were corrected by standard gel densitometry, with BSA stained with coomassie brilliant blue R250 serving as the primary standard. Increases, decreases or no changes in specific activity of the entire library were tabulated for further analysis. FIG. 14 provides a graph showing isoprene synthase activity of kudzu Site Evaluation Library (SEL) members for Y22, A20, and S408 positions. Most members showed highly reduced activity relative to wild type, while conservative substitutions showed less reduction in activity. The activity of variant a20G was close to that of the wild-type pueraria enzyme, indicating that it is a candidate partner for combinatorial mutants. Interestingly, variant S408D of library S408 showed increased activity compared to the wild type, thus providing another candidate partner for combinatorial mutants.

Example 11

Isoprene synthase truncations

This example describes the identification of the amino acid sequence of the protein in the lower duplex band seen in purified poplar IspS preparations (see figure 21). Based on the putative cleavage sites identified by mass spectrometry, a series of amino-terminally truncated IspS molecules were also generated. A shorter amino-terminal truncate of IspS was also generated (the "MEA" truncate in pDu39, see below) to examine the effect of further truncations on IspS activity (Williams DC, McGarvey DJ, Katahira EJ, Croteau R (1998) Biochemistry 37: 12213-.

1. Construction (pDu 27) of amino-terminal 6 XHis-tagged IspS for protein purification

Full length aspen IspS were prepared by PCR from the template aspen pET24a (fig. 19 and 20). The following PCR reactions were tabulated: mu.l (template) -Populus alba pET24a, 5. mu.l 10 XPfuULTRAII Fusion buffer, 1. mu.l dNTP (10mM), 1. mu.l primer (50. mu.M) primer F- (MCM219), 1. mu.l primer (50. mu.M) primer R- (MCM182), 41. mu.l deionised H₂O and 1. mu.l of PfuUltraII fusion DNA polymerase (Stratagene). The PCR cycle parameters were as follows: 29 cycles of 95 ℃ for 1 minute, 55 ℃ for 20 seconds, 72 ℃ for 27 seconds, followed by 72 ℃ for 3 minutes and 4 ℃ until cooling, using an Eppendorf Master cycler. The PCR products were gel extracted and purified according to the manufacturer's recommended protocol using a 0.8% E-gel (Invitrogen) and Qiagen QIA quick gel extraction and QIAprep centrifuge miniprep kit. Mu.l aliquots of the purified product were ligated with pET200D/TOPO vector (Invitrogen) according to the manufacturer's protocol. The reaction was incubated at room temperature for 5 minutes and 6. mu.l of the topoisomerase mixture was subsequently transformed into E.coli Top10 chemically competent cells (Invitrogen) according to the manufacturer's protocol. Transformants were selected on LB plates (Kan50) containing kanamycin (50. mu.g/ml) and incubated overnight at 37 ℃. 5 colonies were picked and screened using PuReTaq Ready-To-Go PCR beads (Amersham) using the T7 forward and MCM182 primers. Clones carrying the correct size insert were further verified by sequencing using the T7 forward primer and T7 reverse primer (Quintara Biosciences). One construct pDu27 (FIGS. 16-18) was selected for further study. Aliquots of 1. mu.l of the plasmid preparation were transformed into BL21 (lambda DE3) pLysS (Invitrogen) according to the manufacturer's protocol. Transformants were selected on LB plates (Cm35) containing Kan50+ and chloramphenicol (35. mu.g/ml) and incubated overnight at 37 ℃. The resulting strain was used to express and purify amino-terminal 6XHis tagged Populus alba IspS.

Purification of 6 XHis-tagged IspS

IspS expressing 6XHis tags

Amino-terminal 6XHis tagged IspS was expressed from strain MD08-99 and purified. This growth method was suitable for histidine-tagged enzymes expressed in BL21(λ DE3) pLysS cells. 10ml overnight cultures were prepared for each 1L planned growth. Appropriate antibiotics (50mg/ml kanamycin, 50mg/ml chloramphenicol and/or 50mg/ml carbenicillin) were added to 10ml LB medium in 25ml flasks and inoculated with 1 colony from fresh cell plates or directly from glycerol frozen cell stocks. The cultures were incubated at 30 ℃ overnight with shaking at about 220 rpm. Diurnal cultures were prepared in 1 liter of LB medium containing the appropriate antibiotics for each culture. Every 1L of diurnal culture was inoculated with 10ml of overnight culture and incubated at 30-37 ℃ with shaking at about 220 rpm until OD₆₀₀To about 0.4-0.6. The diurnal cultures were then induced with 400 μ M IPTG and allowed to continue to grow at 30 ℃ for about 5-6 hours with shaking at about 220 rpm. Cells were then harvested by centrifugation at 10,000Xg for 10 minutes at 4 ℃. After harvesting, the cells were used directly or stored at-80 ℃ until ready for processing.

Purification of 6 XHis-tagged IspS

To purify histidine-tagged enzymes from BL21 (lambda DE3) pLysS cells, the cells were gently resuspended in fresh lysis buffer (lysis buffer: Ni Wash buffer +0.5mM PMSF, 0.01% Tween-20, 1mg/ml lysozyme, 0.2mg/ml DNaseI; Ni Wash buffer: 50mM NaH)₂PO₄300mM NaCl, 20mM imidazole, pH 8.0). Approximately 40-50ml lysis buffer was used per 1L cell pellet. The cells were then incubated on ice for approximately 30 minutes. The cell suspension was then thoroughly lysed 2-3 times through a french press (large french press set at 1200 psi/high) until the lysate began to appear clear. Lysate samples (about 100 μ l) were retained for activity assay and gel analysis. The lysate was subsequently clarified by centrifugation of the lysate in a Sorvall Discovery 90SE ultracentrifuge at 30,000Xg for 30 minutes at 4 ℃. The supernatant was removed and retained. For retentionSamples of "clear lysate" (about 100. mu.l) were analyzed in the activity assay and in the gel.

The clarified lysate was run on a HisTrap HP column (GE Healthcare) using a gradient from 0-100% Ni buffer B. The samples were then analyzed by SDS-PAGE gels (4-12% gel NUPAGE, Invitrogen) according to the manufacturer's instructions. The desired fractions were concentrated on a spin-column filter (Vivaspin-20, Sartoris) and subsequently desalted on a HiPrep 26/10 desalting column (GE heathcare) packed with Sephadex G25 resin. The G-25 buffer consisted of 50mM HEPES, 50mM NaCl and 1mM DTT, pH 7.4. The desired sample was then purified on a HiTrap Q HP column (GE) eluted using a gradient from 0% Q seph buffer A to 100% Q seph buffer B (Q seph buffer A: 50mM Tris, 0.05M NaCl, 1mM DTT, pH 7.6 and Q seph buffer B: 50mM Tris, 1.0M NaCl, 1mM DTT, pH 7.6). Fractions containing the desired protein were analyzed and concentrated. The sample buffer was then exchanged into 50mM HEPES, 50mM NaCl, pH 7.4 containing 1mM DTT by passing the sample through a Hi Prep 26/10 desalting column (GE heathcare) packed with Sephadex G25 resin. A final purification step of gel filtration was used as required. Passing the sample through gel filtration buffer: hi Load 26/60 Superdex 200 preparative Grade (GE) in (50mM HEPES, 150mM NaCl, 1mM DTT, pH 7.4). The fractions were then analyzed and concentrated. The samples were then stored at-80 ℃. In preparation for analysis of the bands, samples were electrophoresed on SDS-PAGE gels (4-12% NUPAGE gel, Invitrogen), stained and the desired bands excised and processed as described below.

Mass spectrometry of isoprene synthase

Sample preparation

In-gel digestion and LCQ-Deca mass spectrometry (modified Rosenfeld gel digestion protocol) was used (Rosenfeld et al, Anal Biochem, (1992)203, 173-. Purified isoprene synthase samples were run on 4-12% SDS-PAGE (NUPAGE, Invitrogen) and incubated with Coomassie Brilliant blue R-250(Thermo Scientific) or SimplyBlue Safe Stain (Invitrogen). The band of interest was cut from the gel and destained. Each gel strip was cut into approximately 1mmx1mm pieces and placed in 0.65mL "smooth" (siliconized) tubes from PGCScientific. Add approximately 100. mu.L of 25mM NH₄HCO₃/50％ACN/H₂O to each tube and vortex mixed for 10 minutes. The supernatant was extracted and discarded. These steps were repeated twice. Subsequently, the gel sheets were treated to dryness in a Savant SpeedVac (about 20 to 30 minutes).

The sample is then reduced and alkylated. For reduction, 25mM NH (freshly prepared) was added₄HCO₃25 μ L (or sufficient coverage) of 10mM DTT to dry gel. The tubes were then vortex mixed and briefly centrifuged. The reaction was incubated at 50 ℃ for 1 hour. For alkylation, the supernatant was removed and 25mM NH added ₄HCO₃To the gel, 25 μ L or more of 55mM Iodoacetamide (IAA). The reaction tube was vortexed and centrifuged briefly again. The reaction was incubated at room temperature for 1 hour in the dark. The supernatant was removed and the gel was incubated with about 100. mu.L of 25mM NH₄HCO₃/50％ACN/H₂The O was washed by vortex mixing for 10 minutes and brief centrifugation. The supernatant was removed and the washing step was repeated once. Subsequently, the gel sheets were dried in a SpeedVac (about 15-30 minutes).

Digestion buffer was prepared by adding 400. mu.L of 0.1% n-octyl B-D-glucopyranosidase water to 100uL of 8M urea. 400uL of this digestion buffer was added to 20ug of freshly prepared trypsin. 0.05. mu.g/. mu.L sequencing grade trypsin was prepared from a vial of 20. mu.g sequencing grade trypsin (Promega) dissolved in 400. mu.L of 1.6M urea solution. A trypsin solution was added sufficient to cover the gel sheet. The tubes were covered with parafilm and incubated overnight (16-20 hours) at 37 ℃. Ensure that there is a small amount of additional buffer above the gel.

The peptides were extracted from the gel by brief vortex mixing and centrifugation of the digest. The digestion solution was transferred to a 0.65mL siliconized tube along with a gel loading tip. Add 50. mu.L (sufficient coverage) of 50% ACN/0.1% FA/H ₂O to gel sheet andand the samples were vortex mixed for 10 minutes, centrifuged and then sonicated for 5 minutes. The extracted peptides were pooled in one tube. The extraction step was repeated 2 to 3 times until the gel sheet became white in appearance and shrunk in size. The extracted digest was vortex mixed, centrifuged and dried in a Speed Vac to a volume of 55 μ Ι _. In the case where the volume is less than 55 μ L, enough 0.1% FA is added to form a final volume of 55 μ L.

Mass spectrometry

Samples were injected onto a Thermofinnigan (San Jose, CA) LCQ-Deca electrospray ionization (ESI) ion trap mass spectrometer. A Vydac C18 column (5. mu.300A, 0.2X150mm, Michrom Bioresources, Auburn, Calif.) was used at a flow rate of 200. mu.L/min. The sample volume was 50uL and was filtered through an in-line trapping cartridge (Peptide Capparp, Michrom Bioresources, Auburn, Calif.) before loading onto the column. The gel mesogens were separated using the following gradient (solvent A: H)₂0.1% trifluoroacetic acid in O (j.t. baker, phillips burg, NJ), solvent B: 0.08% trifluoroacetic acid in acetonitrile (j.t. baker, phillips burg, NJ).

TABLE 11-1 gradiometer

	Minute (min)	A％	B％
				0	0.00	100	0
1	10.00	86	14
				2	16.00	81	19
3	20.00	78	22
				4	21.00	77	23
5	22.00	75	25
				6	24.00	73	27
7	32.00	69	31
				8	34.00	66	34
9	37.00	64	36
				10	47.00	60	40
11	50.00	30	70
				12	55.00	100	0

13	60.00	100	0
				14	65.00	100	0
15		100	0

Mass spectrum results

An aliquot of 6.4. mu.g of protein was loaded onto 5 lanes on 4-12% bis-tris NUPAGE gel (Invitrogen), MOPS buffer and 50 fractions were run. The gel was stained for 2 minutes and subsequently destained for 15 minutes as described above. At H ₂The gel was washed in O and then all bands were cut, cut into small pieces and destained. The gel sheets were reduced and alkylated with DTT/IAA at 52 ℃ and room temperature, respectively, for 1 hour each. Trypsin was added for overnight digestion. The extracted peptides were run on LCQ-Deca. FIGS. 21 and 22 show the results of mass spectrometry analysis. The lower duplex band (in FIG. 21) was identified as IspS. Figure 22 shows that amino-terminal truncation was observed after amino acids 39, 40, 42 and 44 (peptide sequence of IspS protein according to amino-terminal His-tag in pDu 27). The carboxy terminus of IspS is intact.

Construction of amino-terminally truncated IspS variants:

all truncated constructs without affinity tags were generated using the QuickChange site directed mutagenesis kit (Stratagene) using populus alba pET24a template for PCR amplification. Approximately 50ng of template DNA was used to amplify (using an Eppendorf Mastercycler gradient PCR instrument) the mutagenized PCR products using the forward (For) and reverse (Rev) primer pairs corresponding to each truncation involved (e.g., QC MSV For and QC MSV Rev, see Table 11-2). The following PCR reaction mixtures were used: 1 μ l Populus alba pET24a, 5 μ l 10XPfuUltraHF buffer, 1. mu.l dNTP, 1ul (50. mu.M) forward primer (e.g., QC MSV For), 1. mu.l (50. mu.M) reverse primer (e.g., QC MSV Rev), 2. mu.l DMSO, 39. mu.l deionized H ₂O, 1. mu.l of Pfuultra HF polymerase (Stratagene). The following PCR cycle parameters were used: 1 minute at 95 ℃, 30 seconds at 95 ℃, 1 minute at 55 ℃ and 7.3 minutes at 68 ℃ in one cycle; followed by 95 ℃ for 30 seconds, 55 ℃ for 1 minute, 68 ℃ for 7.3 minutes for a total of 18 cycles; and then 4 deg.c. The PCR product was treated with 1-2. mu.l of DpnI (Roche) at 37 ℃ for 1-3 hours. A5. mu.l aliquot of the DpnI-treated product was shown on a 0.8% E-gel (Invitrogen). Aliquots of 1 μ l of each product were transformed into chemically competent E.coli Top10 cells (Invitrogen) according to the manufacturer's protocol. Transformants were selected on LB medium (Kan50) containing kanamycin at a concentration of 50. mu.g/ml and incubated overnight at 37 ℃. 5 colonies per transformation were selected and grown to stationary phase in 3ml of liquid LB Kan 50. Plasmids were purified according to the manufacturer's recommended protocol using the Qiagen miniprep kit. The purified plasmids were sequenced with T7 forward and reverse primers (by Quintara Biosciences) and their corresponding truncations were confirmed. The resulting plasmids (pDU39 to pDU43, see tables 11-4, FIGS. 23-34) were transformed into chemically competent E.coli BL21 (. lamda.DE 3) pLysS (Invitrogen) according to the manufacturer's recommendations. Table X describes strains used to express truncated IspS enzymes.

Using populus alba pET24a as template for the PCR reaction, constructs were generated with an affinity (6 × His) tag and a proteolytic (TEV, tobacco etch virus) tag. The PCR reaction mixture was prepared as follows: 1ul (Populus Alba pET24a), 5ul 10 XPfuUltraII Fusion buffer, 1ul dNTP's (10mM), 1ul primer (50. mu.M) Populus Alba FL-NdeI-For or Alba TRC (MEA) -NdeI-F, 1ul primer (50uM) Alba FLTRC (+) TEV-R, 41ul deionization H₂O and 1ul PfuultraiI fusion DNA polymerase from Stratagene. The PCR cycle parameters were as follows: 95 ℃ for 1 minute, 95 ℃ for 30 seconds, 55 ℃ for 20 seconds, 72 ℃ for 25 seconds, one cycle, and then repeating for additional 28 cycles of 95 ℃ for 30 seconds, 55 ℃ for 20 seconds, 72 ℃ for 25 seconds; followed by 72 ℃ for 3 minutes and then 4 ℃. Amplification and confirmation of the correctness of the product by display on a 0.8% E-gel (Invitrogen)After molecular weight, the PCR product was digested with restriction enzymes NdeI and xhoi (roche) at 37 ℃ for 2 hours and then gel purified using Qiaquick gel purification system (Qiagen) according to the manufacturer's recommended protocol. Mu.l of the purified product was ligated into pET-24a (Invitrogen), wherein the pET-24a was digested with NdeI and XhoI (Roche), gel purified and dephosphorylated according to the manufacturer's recommended protocol (using SAP, shrimp alkaline phosphatase) (Promega). T4 ligase (NEB) was used to ligate the reactions, which were incubated overnight at 16 ℃. The ligation reaction was dialyzed in water for 30 min and 2. mu.l of the reaction was used to electroporate MCM331 (see below) competent cells. Cells were allowed to recover for 2 hours at 30 ℃ and then selected on Kan50 with 5mm (r) - (-) -Mevalonolactone (MVA) (Sigma) spread on the plates. Positive transformations were inoculated into 3ml of liquid LB Kan50 and plasmids were isolated using the QIAprep centrifugal miniprep kit (Qiagen). The insert was verified by restriction digestion using NdeI and xhoi (roche) and positive clones were sequenced with the T7 promoter and T7 terminator sequencing primers (Quintara Biosciences). Mu.l of each plasmid (the plasmids are described in Table 11-4 and FIGS. 35-39) was transformed into chemically competent E.coli BL21 (. lamda.DE 3) pLysS (Invitrogen) according to the manufacturer's recommendations. Transformants were selected on LB Kan50+ Cm35 (chloramphenicol 35ug/ml) plates and incubated at 37 ℃. All expression strains are described in tables 11-5.

Strain MCM331 was prepared as follows. The synthetic operon containing mevalonate kinase, mevalonate phosphate kinase, mevalonate pyrophosphate decarboxylase and IPP isomerase is integrated into the E.coli chromosome. Expression may be altered by incorporating different promoters 5' to the operon, as desired.

i) Targeting vector construction

The attTn7 site was selected for integration. The homologous upstream region (attTn7 up) (primers MCM78 and MCM79) and the homologous downstream region (attTn7 down) (primers MCM88 and MCM89) were amplified by PCR from M1655 cells. Contains 1. mu.L of 10. mu.M primer, 3. mu.L of ddH₂O, 50. mu.L of a reaction of 45. mu.L Invitrogen Platinum PCR Supermix High Fidelity and scraped MG1655 colonies at 9Denaturation at 4 ℃ for 2 min, cycling 25 times (94 ℃ for 2 min, 50 ℃ for 30 sec and 68 ℃ for 1 min), extension at 72 ℃ for 7 min and cooling to 4 ℃. The resulting DNA was cloned into pCR2.1(Invitrogen) according to the manufacturer's instructions, resulting in plasmids MCM278(attTn7 up) and MCM252(attTn7 down). The 832bp ApaI-PvuI fragment digested from MCM252 and gel purified was cloned into ApaI-PvuI digested and gel purified plasmid pR6K, resulting in plasmid MCM 276. The 825bp PstI-NotI fragment digested from MCM278 and gel purified was cloned into PstI-NotI digested and gel purified MCM276, producing plasmid MCM 281.

ii) cloning of downstream pathways and promoters

The MVK-PMK-MVD-IDI gene was amplified from pTrcKKDyIkIS using the Roche Expand Long PCR system with primers MCM104 and MCM105 according to the manufacturer's instructions. This product was digested with NotI and ApaI and cloned into MCM281 which had been digested with NotI and ApaI and gel purified. The CMR cassette was amplified from GeneBridges FRT-gb2-Cm-FRT template DNA using Stratagene Pfu Ultra II with primers MCM120 and MCM 127. For 4 templates containing 1uL of about 10 ng/. mu.L, 1. mu.L of each primer, 1.25. mu.L of 10mM dNTP, 5. mu.L of 10 Xbuffer, 1. mu.L of enzyme and 39.75. mu.L of ddH₂O50 uL PCR reaction the following PCR program was used: denaturation at 95 ℃ for 4 min; 5 cycles of 95 ℃ for 20 seconds, 55 ℃ for 20 seconds, 72 ℃ for 2 minutes; 25 cycles at 95 ℃ for 20 seconds, 58 ℃ for 20 seconds and 72 ℃ for 2 minutes; 72 ℃ for 10 minutes and cooled to 4 ℃. The reactions were pooled, purified on a Qiagen PCR clean column and the washed Pir1 cells containing plasmid MCM296 were washed with electroporation water. Electroporation was performed in a 2ml chamber at 2.5V and 200 ohms. The electroporation reaction was allowed to recover in LB at 30 ℃ for 3 hours. The transformant MCM330 was selected on LA containing CMP5, Kan 50.

iii) integration into the chromosome of E.coli

DNA prepared in minute quantities from MCM330 (Qiaquick Spin kit) was digested with SnaBI and used to electroporate BL21(DE3) (Novagen) or MG1655 containing the GeneBridges plasmid pRedeT Carb. Cells were incubated at 30 ℃ to about OD1, followed by 0.4% L-arabinoseInduction was carried out at 37 ℃ for 1.5 hours. These cells were incubated with ddH at 4 deg.C₂O washes 3 times, followed by electroporation of the transformation with 2. mu.L DNA. The integrants were selected on L agar containing chloramphenicol (5. mu.g/ml) and subsequently demonstrated no growth on L agar + kanamycin (50. mu.g/ml). Frozen BL21 integrant MCM331 and MG1655 integrant MCM 333.

TABLE 11-2 primers

TABLE 11-3 primers used for the construction of Strain MCM331

TABLE 11-4 plasmids for expression of IspS variants

TABLE 11-5 strains expressing IspS variants

Biochemical analysis of IspS truncations

The relative activity of various amino-terminally truncated IspS enzymes was determined by DMAPP assay. The strains described above were analyzed by DMAPP assay in 96-well plates. All strains were assayed in quadruplicate. The "full-length" variant refers to the IspS enzyme expressed from the poplar pET24a plasmid in BL21(λ DE3) plyss (invitrogen).

TABLE 11-6 DMAPP assay of amino-terminal truncations

As a result: table X shows the pairs OD₆₀₀On normalization, strains MD09-173, MD09-175(pDu41), MD09-176(pDu42) and MD09-177(pDu43), which contain plasmid pDu39, all showed higher DMAPP activity than the "full-length" wild-type IspS enzyme (in strain BL21 (. lamda.DE 3) pLysS, which contains Populus alba pET24 a).

Detailed kinetic analysis of "MEA" truncations in IspS

The relative specific activities were determined and the kinetics of the "amino-terminally truncated" poplar isoprene synthase compared to the "full-length" poplar isoprene synthase was examined. 4 strains expressing 4 different constructs were used in this assay: BL21(λ DE3) pLysS containing Populus alba pET24 a; MD 09-173; MD 09-165; and MD09-167 (strain detailed above). These strains expressed "full-length" poplar IspS, "truncated" poplar IspS (MEA truncations), "full-length" carboxy-terminal TEV and His-tagged poplar IspS, and "truncated" carboxy-terminal TEV and His-tagged poplar IspS, respectively. In the experiments described below, "truncation" refers specifically to the MEA variant of populus alba IspS.

All strains were inoculated into LB containing 30mg/L chloramphenicol (Cm) and 50mg/L kanamycin and incubated overnight at 37 ℃ in 2mL culture tubes. The next morning, the overnight cultures were diluted 1: 100 in LB medium containing 30mg/L chloramphenicol (Cm) and 50mg/L kanamycin and incubated at 37 ℃ until the OD was about 0.5. Each strain was grown in triplicate. The culture was then induced with 400uM IPTG and incubated for 4 hours at 30 ℃. 20mL of each culture was centrifuged at 3000Xg for 20 minutes and the supernatant discarded. The pellet was frozen at-80 ℃ overnight. The pellet was resuspended in 2mL of a buffer (pH 8) containing 100mM Tris, 100mM NaCl, 0.25mg/mL lysozyme and 0.25mg/mL DNase. The cell suspension was subjected to 2 french crushes at 20,000psi and the lysate was then centrifuged at 14000xg for 20 minutes to produce a cell-free extract for kinetic studies and protein concentration determination.

To measure specific activity, 5 μ L of cell-free extract from each strain was mixed with 5mM DMAPP, 50mM MgCl in a buffer (pH 8) containing 100mM Tris and 100mM NaCl in 2mL air-tight vials at 30 ℃₂Incubate for 15 minutes to a final volume of 100. mu.L. The reaction was stopped by adding 100. mu.L of 500uM EDTA, pH 8. Samples were analyzed by GC-MS to determine the concentration of isoprene in the vial headspace.

To determine k_catAnd K_M5 μ L of cell-free extract from each strain was mixed with 100mM Tris, 50mM MgCl in 2mL airtight vials at 30 deg.C₂And DMAPP at a concentration in a buffer of 100mM NaCl (pH 8) ranging from 0.625 to 40mM DMAPP for 15 minutes to a final volume of 100. mu.L. The reaction was stopped by adding 100. mu.L of 500mM EDTA, pH 8. Samples were analyzed by GC-MS to determine the concentration of isoprene in the vial headspace. Data were analyzed using Kaleidagraph and fitted to the following equation for noncompetitive substrate inhibition: rate/E ═ k_cat*S/(K_M+S*(1+S/K_i)). All data were treated in triplicate, except for MD09-167 which used 2.5mM DMAPP in duplicate.

Cell-free extracts were electrophoresed on a Caliper microfluidics electrophoresis apparatus (Caliper Life Sciences, Hopkinton, MA, USA) to quantify the amount of isoprene synthase in each sample. According to the manufacturer's instructions (LabChip) HT Protein Express, P/N760301) to prepare microfluidic chips and Protein samples. In 96 hole micro titration plate by adding containing 0.1% Tween 20, 0.1mg/ml lysozyme, 1.0ug/ml DNA enzyme 50mM Tris pH 8.0 at room temperature for 30 minutes, followed by centrifugation, to prepare cultureA nutrient lysate. The supernatants were then transferred to another 96-well plate and stored at-20 ℃ until use, at which time they were thawed at room temperature for 30 minutes. After brief shaking, 2. mu.l of each culture sample was transferred to a 96-well PCR plate (Bio-Rad, Hercules, Calif., USA) containing 7. mu.l of sample buffer (Caliper), followed by heating the plate to 90 ℃ for 5 minutes on a thermostatically controlled plate heater. The plate was allowed to cool, after which 35. mu.l of water was added to each sample. The plate is then placed in the instrument along with the manufacturer supplied and calibrated protein standards. The instrument functions by mixing the sample with a fluorescent dye that is not covalently linked to the protein, followed by electrophoresis through a gel matrix. As the protein moves through one focus of the chip, a fluorescent signal is recorded and protein concentration is determined by quantifying the fluorescent signal relative to the signal generated by the calibrated set of protein standards.

TABLE 11-7. k of isoprene synthase_catAnd K_MAnd specific activity value

Parameters were determined by fitting the data obtained for the following non-competitive substrate inhibition equation to rate/[ E ] vs.

Containing 5mM DMAPP and 50mM MgCl₂Specific activity (S.A.) was calculated for reactions of 100mM Tris, 100mM NaCl and 2.5-4.5. mu.g isoprene synthase from the supernatant of whole cell lysates. Using independently incubated cultures, reactions were performed at 30 ℃ in triplicate for 15 minutes.

Results/discussion:

the specific activity of each protein was determined (FIG. 40 and tables 11-7). The specific activity of the truncated isoprene synthase is approximately 2 times greater than that of the full-length isoprene synthase. Carboxyl-terminal His-tagged full-length isoprene synthase yielded approximately the same specific activity as the full-length isoprene synthase. The carboxy-terminal His-tagged truncated isoprene synthase yielded specific activities that were less than those of the untagged truncated isoprene synthase, but greater than those of the two full-length isoprene synthases.

Analysis of the rate of DMAPP conversion to isoprene over a range of DMAPP concentrations aimed at determining k for the enzyme_catAnd K_MParameters (fig. 41 and 42 and tables 11-7). The enzymes all exhibited a rate profile consistent with non-competitive substrate inhibition by DMAPP. K of full-Length construct _iK greater than truncated constructs_iE.g. by changing K_iAnd observed as determined by the best fit (R-value) to the data (data not shown). All data have a K of 10mM in the graph of this document_iAnd (6) fitting. K of truncated isoprene synthase_MRelative to full-length isoprene synthase. Thus, as the substrate concentration decreased, the ratio between isoprene synthase activities of truncated isoprene synthase and full-length isoprene synthase increased (fig. 43). K of truncated isoprene synthase_catRelative to full-length isoprene synthase. This resulted in greater isoprene synthase activity of the truncated isoprene synthase than the full-length isoprene synthase at all substrate concentrations (fig. 43). The ratio of isoprene synthase activity of truncated isoprene synthase to full-length isoprene synthase was determined at different DMAPP levels (fig. 43).

And (4) conclusion: "truncated" isoprene synthase exhibits increased k for catalyzing the conversion of DMAPP to isoprene compared to "full-length" isoprene synthase_catValue and reduced K_MThe value is obtained. The specific activity of a "truncated" isoprene synthase is increased relative to the specific activity of a "full-length" isoprene synthase. The most active isoprene synthase is the unlabeled truncated isoprene synthase "MEA" variant (in strain MD 09-173). Truncated isoprene synthases may be useful in comparison to full-length isoprene synthases Increasing isoprene synthase activity in an isoprene producing organism.

Example 12

Enrichment-mitigation of DMAPP toxicity by isoprene synthase

This example identifies internal residue alterations in IspS that confer better activity to the enzyme by kinetic improvement, increased expression, increased solubility, or any other means by which DMAPP is more efficiently converted to isoprene by isoprene synthase. This process allows for the reduction of toxic intracellular levels of DMAPP by expression of improved IspS variants. In a population of cells expressing a heterogeneous mixture of IspS variants, the best enzyme should allow better growth of its host strain and should be enriched in the mixed population.

I. Strain construction

The following are the frameworks of strains MCM518-521 and 528-531, where the lambda promoter drives the integrated mKKDyI. Primers MCM120 and MCM224 (Table 12-1) were used to amplify the resistance cassette from GeneBridgesFRT-gb2-Cm-FRT template using the Stratagene Herculase II Fusion kit according to the manufacturer's protocol. 4 50 μ L of the reaction were cycled as follows: 2 minutes at 95 ℃; (95 ℃ for 20 seconds, 55 ℃ for 20 seconds, 72 ℃ for 1 minute) for 30 cycles; 3 minutes at 72 ℃; and 4 ℃ until cooled. 4 reactions were pooled and purified on Qiagen PCR columns according to the manufacturer's protocol and eluted with 60 μ L EB at 55 ℃.

Plasmid pRedeT-carb (GeneBridges) was electroporated into MCM 446. Transformants were recovered by shaking in SOC (Invitrogen) for 1 hour at 30 ℃ and subsequently selected on LB plates (carb50) containing carbenicillin (50. mu.g/ml) overnight at 30 ℃. Carbenicillin resistant colonies were frozen as MCM508 (Table 12-2).

Strain MCM508 was grown from fresh streaks in 5mL LB/carb50 at 30 ℃ to OD₆₀₀About 0.5. 40mM L-arabinose was added and the culture was incubated at 37 ℃ for 1.5 hours. Cells were harvested and electroporated with 3 μ L of purified amplicon as before and subsequently restored to 1.5 ℃ in 500 μ LSOC at 37 ℃-3 hours. Transformants were selected on LB/kan10 plates at 37 ℃.

Recombination of the amplicon at the target locus was confirmed by PCR using primers GB-DW and MCM 208. The resulting amplicons were sequenced to identify 4 clones with the following sequences. The carbenicillin sensitive clone was frozen as strain MCM 518-521.

MCM518-521 was restreaked on LB kan10 plates and incubated overnight at 37 ℃.

Strain MCM518-521 was cultured in LB/kan10 at 37 ℃ and subsequently electro-transformed with plasmid pCP20 (Datsenko KA, Wanner BL. one-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products, Proc Natl Acad Sci USA 6.2000, 6.6.97 (12): 6640-5). Cells were recovered in 500. mu.L SOC shaken at 30 ℃ for 1 hour. Transformants were selected on LB/carb50 plates overnight at 30 ℃. The next morning, colonies from each transformant were incubated at 30 ℃ in liquid LB/carb50 until turbidity was observed. The culture was then moved to 37 ℃ for at least 3 hours. Cells were streaked from this culture onto LB plates and incubated overnight at 37 ℃.

The next day, colonies were supplemented to LB, LB/carb50 and LB/kan 10. Clones did not grow on either carb50 or kan10, and spots from LB were grown in liquid LB and frozen as MCM 528-531.

DNA sequence

These assemblies include the novel promoter inserted on the chromosome of strain MCM518-521 and the origin comprising exactly the mvk ORF. Upstream of these assemblies was the sequence from the GeneBridgesFRT-gb2-Cm-FRT cassette. Downstream is the remainder of the mvk ORF and subsequently the remainder of the downstream MVA pathway integrant from strain MCM 508.

MCM518

aaagaccgaccaagcgacgtctgagagctccctggcgaattcggtaccaataaaagagctttattttcatgatctgtgtgttggtttttgtgtgcggcgc ggaagttcctattctctagaaagtataggaacttcctcgagccctatagtgagtcgtattaaattcatataaaaaacatacagataaccatctgcggt g a taaattatctctggcggtgttgacataaataccactggcggtgatactgagcacatcagcaggacgcactgaccaccatgaaggtgcaaaggaggt aa aa aaacatggtatcctgttctgcgccgggtaagatttacctgttcggtgaacacgccgtagtttatggcgaaactgcaattgcgtgtgcggtggaa

MCM519

aaagaccgaccaagcgacgtctgagagctccctggcgaattcggtaccaataaaagagctttattttcatgatctgtgtgttggtttttgtgtgcggcgcggaagttcctattctctagaaagtataggaacttcctcgagccctatagtgagtcgtattaaattcatataaaaaacatacagataaccatctgcggtgataaattatctctggcggtgttgacctaaataccactggcggtgatactgagcacatcagcaggacgcactgaccaccatgaaggtgcaaaggaggtaaaaaaacatggtatcctgttctgcgccgggtaagatttacctgttcggtgaacacgccgtagtttatggcgaaactgcaattgcgtgtgcggtggaactgcgtacccgtgttcgcgcggaactcaatgactctatcactattcagagc(SEQ ID NO：57)

MCM520

aaagaccgaccaagcgacgtctgagagctccctggcgaattcggtaccaataaaagagctttattttcatgatctgtgtgttggtttttgtgtgcggcgcggaagttcctattctctagaaagtataggaacttcctcgagccctatagtgagtcgtattaaattcatataaaaaacatacagataaccatctgcggtgataaattatctctggcggtgttgacctaaataccactggcggtgatactgagcacatcagcaggacgcactgaccaccatgaaggtgcaaaggtaaaaaaacatggtatcctgttctgcgccgggtaagatttacctgttcggtgaacacgccgtagtttatggcgaaactgcaattgcgtgtgcggtggaactgcgtacccgtgttcgcgcggaactcaatgactctatcactattcagagc (SEQ ID NO：58)

MCM521 (in strains MCM531 and MD 09-171)

aaagaccgaccaagcgacgtctgagagctccctggcgaattcggtaccaataaaagagctttattttcatgatctgtgtgttggtttttgtgtgcggcgcggaagttcctattctctagaaagtataggaacttcctcgagccctatagtgagtcgtattaaattcatataaaaaacatacagataaccatctgcggtgataaattatctctggcggtgttgacgtaaataccactggcggtgatactgagcacatcagcaggacgcactgaccaccatgaaggtgcaaaggaggtaaaaaaacatggtatcctgttctgcgccgggtaagatttacctgttcggtgaacacgccgtagtttatggcgaaactgcaattgcgtgtgcggtggaactgcgtacccgtgttcgcgcggaactcaatgactctatcactattcagagc(SEQ ID NO：59)

neo-PL.2-mKKDyI (from MCM521) was transduced into BL21(λ DE3) to produce strain MD 09-171. A P1 lysate of MCM521 was generated and transduced into BL21 (. lamda.DE 3) according to standard molecular biology techniques (Miller, Short Course in Bacterial Genetics). The transducer was selected on Kan20LB medium plates. Positive colonies were further verified by PCR to confirm the presence of PL.2-mKKDyI in BL21 (lambda DE3) strain. Mu.l of pCP20 plasmid were subsequently transformed into this strain and selected and incubated at 30 ℃ on LB + Carb 50. Positive transformants were then streaked on LB plates and incubated at 37 ℃ to discard the pCP20 plasmid. To confirm the loss of the neomycin (kanamycin) resistance marker, colonies grown at 37 ℃ were inoculated onto LB Kan20, LB Carb50 and antibiotic-free LB plates. Strains that have lost pCP20 with an integrated pl.2mkkkdyi without the kanamycin resistance marker should be sensitive to kanamycin and carbenicillin. The presence of mkkkdyi in BL21(λ DE3) was checked by PCR using 4 Kan sensitive Carb strains, with the parental BL21(λ DE3) strain as a control. Once the presence of mKKDyI was confirmed by PCR, the resulting strain was transformed with 1. mu.l of pLysS plasmid (Invitrogen). The resulting strain MD09-171 was used in enrichment experiments described below.

TABLE 12-1 primers used for Strain construction

TABLE 12-2 strains

Growth inhibition of MCM531 by mevalonic acid

Overnight cultures of MCM531 (see strain description) were re-diluted to OD₆₀₀Is 0.05 (this corresponds to an OD of about 0.005 in a 96-well plate reader)₆₀₀) (SpectraMax M2, Molecular Devices). The diluted culture was then aliquotedStandard TM3 medium (13.6g K) with 0, 1, 5, 10, 15 or 20mM MVA was added to each well in a 96-well deep-well plate₂PO₄，13.6g KH₂PO₄，2.0g MgSO₄*7H₂O), the TM3 medium was supplemented with 1% glucose and 0.8 g/LBiosspringer yeast extract (1% yeast extract final concentration)). Fig. 44 shows the growth curves of MCM531 at various concentrations of MVA. Each MVA concentration was determined in quadruplicate with error bars ignored. FIG. 44 shows that the growth of MCM531 was severely inhibited at 5mM MVA and higher concentrations.

Mutagenesis and selection/enrichment assays of IspS

To generate randomly mutagenized IspS open reading frames, the GeneMorph II EZ Clone domain mutagenesis kit (Stratagene) was used according to the manufacturer's recommendations. Specific primers for amplification of template (Pdu39(pET24 a-Populus alba (MEA))) (Table 12-3, pET24Megaprime Forward and Reverse) are described below. To achieve the desired mutation frequency, the protocol outlined in the genemorphh II kit was followed. To generate 2 to 3 residue changes per molecule, approximately 150ng of starting template DNA was used for the initial PCR reaction. More or fewer templates were used to generate IspS enzymes with fewer or more residue changes, respectively. The resulting mutant "macroprimers" were then used to amplify the remainder of the plasmid according to the manufacturer's recommendations.

The final PCR product from the genemorphh II kit was treated with DpnI according to the manufacturer's recommended protocol. Prior to transformation into E.coli, the PCR reaction needs to be desalted by microdialysis. In general, approximately 20. mu.l of the PCR reaction was microdialysed and used for electroporation by standard molecular biology methods into the strain MD09-171 (Table 12-2). After electroporation, the cells were recovered at 30 ℃ for 2 hours and then plated on LB medium Kan50 Cm 35. The entire transformation volume was plated to recover all mutations generated by this mutagenesis method.

For enrichment, all transformants were scraped and pooled together. Aliquots from each pool were frozen for storage at-80 ℃. Before enrichment, the strains (pairs)Photograph or experimental pool) were inoculated directly into LB containing Kan50 and incubated for several hours to minimize loss of pool heterogeneity. After this recovery period, cells were diluted into liquid TM3 medium (described above) containing Kan50, 5mM MVA and 200 μ M IPTG. (for each pool/media source/control reaction, the exact dilution was determined empirically). The culture was then placed in a shaking incubator at 34 ℃ until OD₆₀₀Not more than 5. At this point, the plasmid was purified from 1ml of "enriched" culture by a microfabrication protocol (Qiagen). This plasmid preparation was subsequently transformed into electrocompetent MD09-171 cells as described above. Transformed cells were recovered in antibiotic-free LB medium for 2 hours and then enriched in subsequent rounds by dilution into TM3 containing Kan50, 5mM MVA and 200 μ M IPTG as described above. As described above, the culture was placed in a shaking incubator at 34 ℃ until it reached an OD of not more than 5 ₆₀₀. The plasmid was subsequently purified, retransformed and subjected to a further round of "enrichment". The enrichment process was continued for 5 or 6 rounds of selection, plasmid purification and retransformation. This process continues until the culture is homogeneous, i.e., contains only one IspS variant as indicated by sequencing analysis.

After the final round of enrichment, plasmid pools were transformed into chemically competent E.coli Top10 cells (Invitrogen), recovered, plated on LB medium with Kan50 and sent for complete sequencing (Quintara Biosciences) to compare with the wild-type sequence of Populus alba IspS, according to the manufacturer's recommendations. Primers used for sequencing are described below:

TABLE 12-3 primers for IspS mutagenesis and sequencing

pET24 Megaprime Forward	gtttaactttaagaaggagatatacat
		pET24 Megaprime reverse	gagctcgaattcggatcctta
Populus alba sequencing reverse	ctcgtacaggctcaggatag
		Populus alba sequencing reverse 2	ttacgtcccaacgctcaact
EWL1000	gcactgtctttccgtctgctgc
		QB1493	cttcggcaacgcatggaaat

Individual residue changes identified by enrichment/DMAPP toxicity mitigation:

plasmids isolated from the selection/enrichment process were completely sequenced. The following residue changes were confirmed by sequencing (Quintara Biosciences). The residue numbering corresponds to the Populus alba "full-length" sequence (in Populus alba pET24 a; SEQ ID NO: 120), wherein the initial methionine is amino acid number 1. The identified residue changes include: V10M, F12S, T15A, E18G, V58I, V58F, L70Q, L70V, T71V, V79V, E89V, G94V, S119V, F120V, G127V, E175V, T212V, S257V, R262V, a 266V, F280V, N297V, F305V, L319V, E323V, a V, D36342, a 359V, K366V, E368V, L374V, S396V, V418V, K V, H36438 72, T V, T442V, I449V, a 469V, K500V, K V, G V, S36509, S V, N507 36511, and N532V.

Combinations of residue changes (in individual IspS enzymes) identified by enrichment/DMAPP toxicity mitigation included: G127/F511, L70/G94/R262/F305, F12/T15/E18/N297, S396/T442, V10/E323, F120/A266, K438/K500, V79/S509, E175/S257/E368/A469, T71/L374, F280/H440, E89/H440, V58/A328/N532, S119/D342/I449 and K366/G507.

Example 13

Construction of site-saturated library (SSL) and biochemical analysis of L70R variants

This example includes an examination of the effect of possible amino acid substitutions at the sites identified by the selection/enrichment method described above and at other potential sites of interest (active sites, conserved between populus species) on the solubility, expression and activity of IspS.

I. Strain construction

Residues identified by the selection/enrichment method described above (L70, G94, R262, F305) were selected for analysis. In addition, residues putatively involved in substrate binding (F303, V3065, F385, S412, Q416, F450) and residues that differ between the various poplar species (e.g. V418, T442) were selected for further analysis (numbering corresponding to the "full length" amino acid sequence of the poplar IspS). To generate a randomized pool of amino acid substitutions (site-saturated library, SSL), pDu39 (see description above) was subjected to QuickChange (Stratagene) mutagenesis using QC primers shown below (Table 13-1) according to the manufacturer's recommendations. The PCR reactions were prepared as follows:

Mu.l of pDU39, 5. mu.l of 10 XPfuultra HF buffer, 1. mu.l of dNTP, 1. mu.l (50. mu.M) of forward primer (e.g.QCL 69F), 1. mu.l (50. mu.M) of reverse primer (e.g.QCL 69R), 2. mu.l of DMSO, 39. mu.l of deionised H₂O and 1. mu.l of Pfuultra HF polymerase (Stratagene). The PCR cycle parameters for QuickChange are as follows: 95 ℃ for 1 minute, 95 ℃ for 30 seconds, 55 ℃ for 1 minute, 68 ℃ for 7.3 minutes, one cycle, followed by 95 ℃ for 30 seconds, 55 ℃ for 1 minute, 68 ℃ for 7.3 minutes, 17 additional cycles. The temperature was then reduced to 4 ℃. The incorporation of the base NNK at the codon of the above-mentioned residue allows the insertion of codons representing all 20 possible amino acids at a given site. Mu.l of the resulting pool of mutagenized PCR products (supra)Described) DpnI and transformed into chemically competent E.coli Top10 cells (Invitrogen) according to the manufacturer's recommendations. All transformation reactions were recovered in antibiotic-free 1ml LB medium at 37 ℃ for 1 hour and plated on LB Kan 50. The next day, all transformants were scraped off LB plates, mixed thoroughly and the plasmid purified by miniprep (Qiagen). The plasmid pool was subsequently transformed into chemically competent BL21 (. lamda.DE 3) pLysS cells (Invitrogen) according to the manufacturer's protocol. The transformation reaction was recovered in 1ml of LB medium at 37 ℃ for 1 hour and then plated to LB Kan50 Cm35 at a dilution sufficient to cause isolation of positive colonies. After overnight incubation at 37 ℃, each colony was inoculated into each well of a 96-well deep-well microtiter plate (VWR) containing 500ul of liquid LB Kan50 Cm35 each. In 8 wells (generally column 12, A to H), the strains MD09-173 (see above) or BL21(λ DE3) pLysS containing Populus alba pET24a (full length) were inoculated as controls for the DMAPP assay. The microtiter plates were then sealed with a semipermeable membrane (Breathe-Easier, modified Biotech) and incubated overnight at 30 ℃ in a shaking incubator (Vertiga). The following day, 100 μ l samples from each well in one 96 well plate were mixed with 50 μ l 50% glycerol in one 200ul new 96 well plate and frozen at-80 ℃ until further analysis. The plate was then used for the DMAPP assay described below.

TABLE 13-1 primers for mutagenesis

QC L70F	gaaaaagcagaatttnnkaccctgctggaactg (SEQ ID NO：68)
		QC L70R	cagttccagcagggtmnnaaattctgctttttc (SEQ ID NO：69)
QC G94F	gagtctgatatccgtnnkgcgctggatcgcttc (SEQ ID NO：70)
		QC G94R	gaagcgatccagcgcmnnacggatatcagactc (SEQ ID NO：71)
QC R262F	tcccgttggtggcgtnnkgtgggtctggcgacc (SEQ ID NO：72)

QC R262R	ggtcgccagacccacmnnacgccaccaacggga (SEQ ID NO：73)
		QC F303F	tccgtcgcaaaaatgnnktctttcgtaaccatt (SEQ ID NO：74)
QC F303R	aatggttacgaaagamnncatttttgcgacgga (SEQ ID NO：75)
		QC F305F	gcaaaaatgttttctnnkgtaaccattatcgac (SEQ ID NO：76)
QC F305R	gtcgataatggttacmnnagaaaacatttttgc (SEQ ID NO：77)
		QC V306F	aaaatgttttctttcnnkaccattatcgacgat (SEQ ID NO：78)
QC V306R	atcgtcgataatggtmnngaaagaaaacatttt (SEQ ID NO：79)
		QC F385F	gacctgtgcaacgctnnkctgcaagaagccaag (SEQ ID NO：80)
QC F385R	cttggcttcttgcagmnnagcgttgcacaggtc (SEQ ID NO：81)
		QC S412F	gcatggaaatcctctnnkggcccgctgcaactg (SEQ ID NO：82)
QC S412R	cagttgcagcgggccmnnagaggatttccatgc (SEQ ID NO：83)
		QC Q416F	tcttctggcccgctgnnkctggtgttcgcttac (SEQ ID NO：84)
QC Q416R	gtaagcgaacaccagmnncagcgggccagaaga (SEQ ID NO：85)
		QC V418F	ggcccgctgcaactgnnkttcgcttacttcgct (SEQ ID NO：86)
QC V418R	agcgaagtaagcgaamnncagttgcagcgggcc (SEQ ID NO：87)
		QC T442F	caaaaataccatgacnnkatctctcgtccttcc (SEQ ID NO：88)
QC T442R	ggaaggacgagagatmnngtcatggtatttttg (SEQ ID NO：89)
		QC F450F	cgtccttcccatatcnnkcgtctgtgcaatgac (SEQ ID NO：90)
QC F450R	gtcattgcacagacgmnngatatgggaaggacg (SEQ ID NO：91)

Generating "winner" plates for the second assay and identifying L70R as variants with increased specific activity

Variants were selected for further analysis, wherein the variants exhibited increased specific isoprene production compared to the wild type. Figure 45 shows a typical dataset for SSL plates for a single residue (in this case L70). From this particular plate, samples in wells C3(27), D3(39) or E3(51) were selected for further analysis. When DMAPP analysis was performed, other variants at different residues (listed above) that showed increased isoprene production were isolated from their original SSL plates (described above) stored at-80 ℃ and re-arrayed onto one "winner" plate for a second screen. Two wells containing MD09-173 were included as controls. All variants were sequenced (Quintara Biosciences) and performed as described aboveDMAPP assay. The sequence results are shown in Table 13-2. For the DMAPP assay, single growth of each variant was assayed and thus a single lysate was generated, but in quadruplicates to generate statistically significant data. OD of sample shown in Table 13-2₆₀₀And (4) measuring. All lysates were subjected to protein analysis using the Western Breeze Western blotting kit (Invitrogen) followed by fluorescent detection of Storm860 (see below).

DMAPP assay-growth, lysis and isoprene measurement

Plaque plates were prepared from overnight glycerol stock plates using VP-Scientific Replication Tool patch LB agar CM35/Kan50 Large plaque plates. The cultures were incubated overnight (20 to 24 hours) at 30 ℃. The plates were stored at 4 ℃ for up to one week.

Overnight growth plates were prepared from 500mL LB CM35/Kan50 medium. 300 μ L/well LB CM35/Kan50 medium was dispensed into deep 96 well plates. Plaque inoculum was transferred to deep 96-well plates using a V & S replication tool. The medium was inoculated by dipping the tool and then shaking the needle inside the well. The overnight growth plates were sealed with a Breathe-Easier sealing membrane. The plates were incubated overnight at 800 rpm for 16 to 18 hours at 30 ℃ in a Vertiga Shaking incubator.

Deep 96 well diurnal growth plates were prepared by partitioning into 588. mu.L/well of LB CM35/Kan50 medium. The overnight growth plates were removed from the incubator and the cultures were diluted 50-fold. 12 μ L of overnight culture was transferred to diurnal growth plates containing 588 μ L/well of supplemented LB medium. The overnight growth plates were sealed with a fresh piece of Breathe-Easier sealing film and incubated at 34 ℃ and 800 rpm in a Vertiga shaker incubator for 2.25 hours.

To induce expression of IspS, thawed 12mM IPTG was poured into a 50mL or 100mL sterile reservoir and dispensed at 20. mu.L/well into each 600. mu.L/well culture. The overnight growth plate was resealed with a Breathe-Easier seal film and incubated at 34 ℃ and 800 rpm in a Vertiga shake incubator for 4 hours.

To harvest the cells, 200. mu.L of the induced culture was transferred to 450. mu.L Nunc storage plates. The plate was centrifuged at 3300 rpm for 20 minutes at 4 ℃ in a low speed bench top centrifuge. Remove 180 μ L of supernatant with a pipette and discard. The plates were sealed with aluminum foil membrane, covered with a plastic plate lid and stored frozen at-80 ℃.

Read the OD of the plate₆₀₀. 150 μ L of 1xPBS was dispensed into 96-well Costar Read plates (# 9017). Subsequently 50 μ L of culture samples were transferred to the Read plate. OD was then taken with a Spectramax plate reader₆₀₀And (6) reading.

Cracking: the harvested plates were thawed in a room temperature water bath for 4 minutes and then incubated in a hot mixer at 25 ℃ for 1 minute at 1200 rpm. Lysis buffer was dispensed at 80. mu.L/well into 20. mu.L/well of harvested cells. From 6.25ml 1M Tris pH8, 625. mu.l 10% Tween 20, 312.5. mu.l 0.2M PMSF, 462.5. mu.l 10mg/ml DNase I (Sigma), 1.25ml 1M MgCl ₂132.5. mu.l 25000U/. mu.l lysozyme (Epicentre Technologies) and 40.968ml deionised H₂O1.25 Xlysis working stock buffer. The plates were incubated at 1200 rpm for 30 minutes in a thermal mixer at 25 ℃. By deionizing H with 4.75ml₂A stock of 1 Xlysis buffer was prepared by O dilution of 19ml of 1.25 Xlysis working stock.

The DMAPP working stock was prepared as follows:

the diluent was 0.1M potassium phosphate. Dispense 200 uL/well for transfer to sample wells and store on ice.

DMAPP reaction: 1 × lysis buffer was dispensed at 65 μ L/well. Transfer 15. mu.L/well lysate to each sample well in a 96-well Zeiss Glass Block (Zinsser Glass Block). DMAPP reagent was dispensed at 20. mu.L/well. The glass blocks were sealed with aluminum foil film and incubated at 450 rpm for 45 minutes at 25 ℃. The reaction was terminated by transferring the glass block to a 70 ℃ water bath and incubating for 6 minutes. GC analysis was performed as described previously.

Western blotting of pentadiene synthase with fluorescently labeled secondary antibody

Samples were prepared and subjected to native PAGE^TM NovexBis-Tris gels (Invitrogen) were run according to the manufacturer's protocol. After completion of electrophoresis, XCell II was used^TMThe Blot Module (Invitrogen) transferred the gel immediately to nitrocellulose membrane according to the manufacturer's recommendations. After transfer, the membrane was placed in 15ml of a suitable blocking solution (ultrafiltration water 31.5ml, blocking/diluent (part a) 9ml, blocking/diluent (part B) 4.5ml) in a plastic dish with a lid provided in the kit and incubated for 30 minutes on a rotary shaker set at 1 rpm. The blocking solution was decanted and the membrane was rinsed 2 times with 20ml of water, each for 5 minutes. The membrane was incubated with 15ml of primary antibody (Ab) solution (24. mu.l of primary antibody in 15ml of blocking solution) for 1 hour, followed by 3 washes with 20ml of 1 Xantibody wash for 5 minutes. This membrane was then incubated with 15ml of secondary antibody solution (15 ul of secondary antibody (Alexa Fluor 488 goat anti-rabbit IgG (H + L, Invitrogen)) in 15ml of blocking solution for 30 min. The membrane was washed 3 times with 20ml antibody wash for 5 minutes each and rinsed 2 times with 20ml water for 2 minutes. The film was dried between absorbent papers and stored at room temperature for further testing. Fluorescent bands were detected and quantified using Storm 860 Molecular Imager (GMI, Inc).

V. results:

table 13-2 shows all relevant data for each variant tested: sequencing results (of all 4 replicates), residue changes, average isoprene production, protein concentration and average specific activity. FIG. 46 shows a graphical representation of the data shown in Table 13-2. The specific activity was calculated by multiplying the produced isoprene (. mu.g/l) by 0.0414 and then dividing by the protein concentration (mg/ml). The conversion factor (0.0414) represents the total headspace volume (1.9ml), lysate volume (15ul), duration of the DMAPP assay (45 minutes) and isoprene molecular weight in a 2ml sealed GC vial. Thus, specific activity values are given in nmol isoprene/mg Isps/min.

The data in table 13-2 and the graph of fig. 46 show that all variants analyzed, all 3L 70R variants, exhibited higher specific activity than the wild type. To further analyze the L70R variants, the specific activity values of all 3 isolates (in quadruplicate) were averaged and compared to a control (2 isolates, each in quadruplicate). Thus, there are 12 metric values for the L70R variant and 8 metric values for the wild type. These data are shown below in tables 13-3. The L70R variant showed a 25% increase in activity over MD09-173(MEA truncations) when corrected for protein. Figure 47 shows the average specific activity of all L70R variants compared to MEA. Error bars represent one standard deviation. Two sets of L70R and MEA controls were subjected to the student T-test for statistical analysis, which yielded a P-value of 6.0011X 10 ^-5。

TABLE 13-2 sequencing results of all residues in winner plate, isoprene production, protein concentration and specific activity

It should be noted that the entire plasmid sequence is identical to Pdu39 except for the codons indicated (see above). The L70R variant is highlighted in grey.

TABLE 13-3 average specific Activity of all L70R variants relative to MEA control

Variant averaging	Specific activity	Standard deviation of
			L70R	365.116	35.31977

WT (MEA control)

294.7809

17.19228

The bar graph is shown in FIG. 47.

Example 14

Truncation of Populus alba, Populus deltoides, Populus trichocarpa and Pueraria lobata synthases

This example describes the production of a series of truncations in the IspS enzymes of populus alba, populus deltoids, populus trichocarpa and pueraria lobata and determines their effect on activity.

I. Strain construction

All isoprene synthase genes were codon-optimized for E.coli from DNA2.0(Menlo Park, CA), synthesized and cloned into pET24 a. Using the QuickChange site directed mutagenesis kit (Stratagene), the template was amplified using PCR as described previously: populus alba pET24a (for plasmids pDu47-3 to-7, FIGS. 48, 49, 51-60), Populus deltoides pET24a (plasmid pDu48, FIGS. 49C, 61 and 62), Populus tomentosa pET24a (pDu49, FIGS. 50A, 63, 64) or pET24 d-Kudzuvine (pDu 50)And 50-4, FIGS. 50B, 50C, 65-68), all truncated constructs were generated. Approximately 50ng of template DNA was used to amplify (using an Eppendorf Mastercycler gradient PCR instrument) PCR products using the forward (For) and reverse (Rev) primer pairs (QC Trunc-3F and QC Trunc-3R, see, For example, Table 14-1) corresponding to each truncation involved. The PCR reaction mixture was as follows: mu.l Populus alba pET24a (or other template), 5. mu.l 10 XPfuultra HF buffer, 1. mu.l dNTP (10mM), 1. mu.l (50uM) forward primer, 1. mu.l (50. mu.M) reverse primer, 1.5. mu.l DMSO, 39.5. mu.l deionised H ₂O and 1. mu.l of Pfuultra HF polymerase. The PCR cycle parameters were as follows: (95 ℃ for 1 min, 55 ℃ for 1 min, 68 ℃ for 7.30 min) 18 cycles, followed by 4 ℃ until cooling, using an Eppendorf Mastercycler Gradient Machine. The PCR product was treated with 1-2. mu.l of DpnI (Roche) at 37 ℃ for 1-3 hours. Mu.l of DpnI-treated product are shown on a 0.8% E-gel (Invitrogen). Mu.l of each product (according to the manufacturer's protocol) were transformed into chemically competent E.coli Top10 cells (Invitrogen). Transformants were selected on LB medium (Kan50) containing kanamycin at a concentration of 50. mu.g/ml and incubated overnight at 37 ℃. 5 colonies per transformation were selected and grown to stationary phase in 3ml of liquid LB Kan 50. The plasmid was purified according to the manufacturer's recommended protocol using the QIAPrep centrifugation miniprep kit (Qiagen). The purified plasmids were sequenced with T7 forward and reverse primers (by Quintara Biosciences), compared to the parental sequences, and their corresponding truncations were confirmed. The resulting plasmids (pDU47-3 to pDU50-4, see Table 14-2) were transformed into chemically competent E.coli BL21(DE3) pLysS (Invitrogen) according to the manufacturer's recommendations. Tables 14-3 describe strains for expression of truncated IspS enzymes.

After overnight incubation at 37 ℃, each colony was inoculated into each well of a 96-well deep-well microtiter plate (VWR) containing 500ul of liquid LB Kan50 CM35, respectively. The microtiter plates were then sealed with a semipermeable membrane (Breathe-Easier, Diversified Biotech) and incubated overnight at 30 ℃ in a shaking incubator (Vertiga). The following day, 100 μ l samples from each well in one 96 well plate were mixed with 50 μ l 50% glycerol in one 200ul new 96 well plate and frozen at-80 ℃ until further analysis. The plate was then used in a DMAPP assay as described in example 13. Tables 14-4 show the average specific productivity for all samples and figure 69 shows a graphical representation of the same data.

DMAPP activity and protein quantification were determined as described in example 13.

Specific activity was calculated by multiplying the produced isoprene (. mu.g/l) by 0.00776 and dividing by the protein concentration (mg/ml). The conversion factor (0.00776) represents the total headspace volume (1.9ml), lysate volume (80 μ l), duration of the DMAPP assay (45 minutes) and isoprene molecular weight in a 2ml sealed GC vial. Thus, specific activity values are given in nmol isoprene/mg Isps/min.

TABLE 14-1 primers

QC Trunc-3F	gaaggagatatacatatgaccgaagctcgtcgt (SEQ ID NO：92)
		QC Trunc-3R	acgacgagcttcggtcatatgtatatctccttc (SEQ ID NO：93)
QC Trunc-4F	gaaggagatatacatatggaaaccgaagctcgt (SEQ ID NO：94)
		QC Trunc-4R	acgagcttcggtttccatatgtatatctccttc (SEQ ID NO：95)
QC Trunc-5F	gaaggagatatacatatgactgaaaccgaagct (SEQ ID NO：96)
		QC Trunc-5R	agcttcggtttcagtcatatgtatatctccttc (SEQ ID NO：97)
QC Trunc-6F	gaaggagatatacatatggaaactgaaaccgaa (SEQ ID NO：98)
		QC Trunc-6R	ttcggtttcagtttccatatgtatatctccttc (SEQ ID NO：99)
QC Trunc-7F	gaaggagatatacatatgaccgaaactgaaacc (SEQ ID NO：100)
		QC Trunc-7F	ggtttcagtttcggtcatatgtatatctccttc (SEQ ID NO：101)
QC Kudzu MEA F	agaaggagatataccatggaagctcgtcgttccgcaaac (SEQ ID NO：10)
		QC Kudzu MEA R	gtttgcggaacgacgagcttccatggtatatctccttct (SEQ ID NO：103)
QC Kudzu-4F	agaaggagatataccatggagcataattcccgt (SEQ ID NO：104)
		QC Kudzu-4R	acgggaattatgctccatggtatatctccttct (SEQ ID NO：105)
QC Trem/Trich-2F	gaaggagatatacatatggaaacgcgtcgttct (SEQ ID NO：106)
		QC Trem/Trich-2R	agaacgacgcgtttccatatgtatatctccttc (SEQ ID NO：107)

TABLE 14-2 plasmids

pDu47-3	Mtg pET24a-P.alba TRC(-3)
		pDu47-4	Mtg pET24a-P.alba TRC(-4)
pDu47-5	Mtg pET24a-P.alba TRC(-5)
		pDu47-6	Mtg pET24a-P.alba TRC(-6)
pDu47-7	Mtg pET24a-P.alba TRC(-7)
		pDu48	Mtg pET24a-P.tremu TRC(MET)
pDu49	Mtg pET24a-P.tricho TRC(MET)
		pDu50	Mtg pET24d-Kudzu TRC(MEA)
pDu50-4	Mtg pET24d-Kudzu TRC(-4)

TABLE 14-3 strains

MD09-197-3	BL21(DE3)pLysS，pDu47-3
		MD09-197-4	BL21(DE3)pLysS，pDu47-4
MD09-197-5	BL21(DE3)pLysS，pDu47-5
		MD09-197-6	BL21(DE3)pLysS，pDu47-6
MD09-197-7	BL21(DE3)pLysS，pDu47-7
		MD09-198	BL21(DE3)pLysS，pDu48
MD09-199	BL21(DE3)pLysS，pDu49
		MD09-200	BL21(DE3)pLysS，pDu50
MD09-200-4	BL21(DE3)pLysS，pDu50-4

TABLE 14-4 specific Productivity of the variants listed above

A second experiment was performed with the strains listed in Table 14-5. The control was BL21 DE3 pLysS containing Populus alba pET24a (full length Populus alba IspS).

TABLE 14-5 strains

MD09-197-3	BL21(DE3)pLysS，pDu47-3
		MD09-197-4	BL21(DE3)pLysS，pDu47-4
MD09-197-5	BL21(DE3)pLysS，pDu47-5
		MD09-197-6	BL21(DE3)pLysS，pDu47-6
MD09-197-7	BL21(DE3)pLysS，pDu47-7
		MD09-198	BL21(DE3)pLysS，pDu48
MD09-199	BL21(DE3)pLysS，pDu49
		MD09-173	BL21(DE3) pLysS, pET24a-P.alba (MEA) unlabeled (pDu39)
MD09-174	BL21(DE3) pLysS, pET24a-P.alba (MNV) unlabeled (pDu40)

MD09-175	BL21(DE3) pLysS, pET24a-P.alba (MSV) unlabeled (pDu41)
		MD09-176	BL21(DE3) pLysS, pET24a-P.alba (MTE) unlabeled (pDu42)
MD09-177	BL21(DE3) pLysS, pET24a-P.alba (MVS) unlabeled (pDu43)
		MD09-197-3	BL21(DE3)pLysS，pDu47-3
MD09-197-4	BL21(DE3)pLysS，pDu47-4

Results

All truncations of aspen IspS and two truncations from aspen americana and populus trichocarpa were assayed in parallel to compare their relative specific activities by DMAPP assay and quantitative western blotting. At least 2 samples of each variant were assayed for isoprene production and the amount of IspS (mg/ml). The variant MD09-174 produced low amounts of isoprene and expressed low amounts of protein, but showed high specific activity. MD09-173, MD09-176, and MD09-197-3 also showed high specific activities (see Table 14-6 and FIG. 70). MD09-176 and MD09-197-3 showed the highest level of protein (μ g) among 3 μ g total protein, indicating that these variants are more efficiently expressed in E.coli BL21 DE3 host strain.

TABLE 14-6 specific Activity of truncates

Bacterial strains	Average specific Activity	Standard deviation of	Mean ugIspS/3. mu.g total protein
				Populus alba FL	240.16239	31.0423851	0.198
MD09-175	331.8755329	8.958408319	0.188
				MD09-177	340.1959506	39.72104203	0.150
MD09-176	363.516921	3.376026129	0.202
				MD09-174	452.7792122	27.71567075	0.018
MD09-197-7	279.2042431	23.82331163	0.158
				MD09-197-6	309.8357305	7.903564316	0.164
MD09-197-5	293.22592	20.97161876	0.165
				MD09-197-4	321.3926574	56.13760028	0.186
MD09-197-3	333.0604155	45.92710529	0.207
				MD09-173	368.4597405	37.80631246	0.159

MD09-198	297.6476631	56.81405985	0.154
				MD09-199	256.7342861	8.239697653	0.216

Example 15

Constructs for three-dimensional structure determination

Construction of pMAL-C4X Kudzu

A synthetic gene encoding kudzu (Pueraria lobata) isoprene synthase (IspS) and codon-optimized for E.coli was purchased from DNA2.0(Menlo Park, CA), and provided as plasmid p9795 (FIGS. 71 and 72). This insert was excised by BspLU111I/PstI digestion, gel purified and religated into NcoI/PstI-digested pTrcHis2B (Invitrogen, Carlsbad, Calif.). The obtained plasmid was designated as pTrcKudzu (FIG. 73: map of pTrcKudzu). The stop codon in this insert precedes the PstI site, which results in a construct in which the His tag is not attached to the IspS protein.

PCR reactions were carried out to amplify E.coli codon-optimized Kudzuvine gene using plasmid pTrcKudzu as DNA template, primers EL-959 and EL-960, 10mM dNTP (Roche, Indianapolis, IN) and Pfu Ultra II Fusion DNA polymerase (Stratagene, La Jolla, CA) according to the manufacturer's protocol. The PCR conditions were as follows: 2 min at 95 ℃ (first cycle only); repeating 28 cycles at 95 ℃ for 25 seconds, 60 ℃ for 25 seconds, and 72 ℃ for 30 seconds; final extension at 72 ℃ for 1 min. The PCR products were subsequently purified using the QIAquick PCR purification kit (Qiagen Inc, Valencia, CA).

The kudzu PCR product (1. mu.g) was digested with EcoRI and HindIII restriction endonucleases (Roche) according to the manufacturer's protocol. The digestion product was incubated at 37 ℃ for 30 minutes to minimize digestion of the internal EcoRI site present in the kudzu gene. The digested PCR fragment was then purified using QIAquick PCR purification kit. The vector pMAL-C4X (0.5. mu.g) (New England Biolabs, Ipshow, MA; FIGS. 75 and 76) was digested with EcoRI and HindIII restriction endonucleases (Roche) according to the manufacturer's protocol. The digested vector was then gel purified using a QIAquick gel extraction kit (Qiagen Inc). DNA ligation was performed using T4D NA ligase (New England Biolabs) at a 5: 1 ratio of digested Kudzuvine PCR product to digested pMAL-C4X vector according to the manufacturer's protocol. An aliquot of the ligation reaction was then transformed into TOP10 chemically competent cells (Invitrogen Corp). Transformants were selected on LA + 50. mu.g/. mu.l carbenicillin plates.

The selection of transformants containing the pueraria gene is carried out as follows: colonies were picked and PCR was performed using PuReTaq Ready-To-Go PCR beads (GE Healthcare, Piscataway, NJ) with primers EL-957 and EL-966 according To the manufacturer's protocol. The PCR conditions were as follows: 2 min at 95 ℃ (first cycle only); repeating 28 cycles at 95 ℃ for 30 seconds, 50 ℃ for 30 seconds, and 72 ℃ for 40 seconds; final extension at 72 ℃ for 1 min. The PCR products were analyzed on a 2% E-gel (Invitrogen Corp) looking for a 600bp fragment. Colonies containing the correct size PCR product insert were submitted for DNA sequencing using primers EL-950, EL-951, EL-953 and EL-957. DNA sequencing confirmed the construction of plasmid pMAL-C4X Kudzu (FIGS. 77-79).

TABLE 15-1 primer sequences

Plasmid pMAL-C4X Kudzzu was transformed into OneShot BL21 (. lamda.DE 3) chemically competent cells (Invitrogen Corp). Transformants of the expression strain were selected on LA +50mg/ml carbenicillin plates.

IspS variants for Crystal Structure testing

This example describes methods for generating affinity tagged isoprene synthase (IspS) enzymes for expression, purification and crystallization.

Strain construction

For the construct in pET200D-TOPO vector (Invitrogen), the PCR products of the IspS enzyme from Populus alba, Populus tremula and Populus tomentosa were gel extracted and purified (Qiagen) using a 0.8% E-gel (Invitrogen) according to the manufacturer's recommendations. The PCR reaction for the pET200 construct was as follows: the reaction mixture was 1. mu.l (template) -pET24 a-Populus alba, 5. mu.l 10 XPfuUltraII Fusion buffer, 1. mu.l dNTP (10mM), 1. mu.l primer (50uM) forward primer (MCM219 or 218), 1. mu.l primer (50uM) reverse primer (MCM182), 41. mu.l deionised H₂O and 1. mu.l of PfuUltraII Fusion DNA polymerase from Stratagene; the cycling parameters were 95 ℃ for 1 minute, 55 ℃ for 20 seconds, 72 ℃ for 27 seconds, 29 cycles, followed by 72 ℃ for 3 minutes and then 4 ℃ until cooling, using an Eppendorf Mastercycler. Similar reactions were carried out on populus deltoids, populus trichocarpa and pueraria lobata. Mu.l of the purified product was then ligated with pET200D/TOPO vector (Invitrogen) according to the manufacturer's protocol. The reaction was incubated at room temperature for 5 minutes and 6. mu.l of the topoisomerase mixture was subsequently transformed into E.coli Top10 chemically competent cells (Invitrogen) according to the manufacturer's protocol. Transformants were selected on LB Kan50 plates and incubated overnight at 37 ℃. 5 colonies were picked for each construct and screened using PuReTaq Ready-To-Go PCR beads (Amersham) using T7 forward and MCM182 primers (Table 15-2). Clones carrying inserts of the correct size were further verified by centrifugation of plasmid minipreps using QIAprep (Qiagen) followed by sequencing with the T7 forward primer and the T7 reverse primer (Quintara Biosciences). One fully sequenced construct (for details and sequence/figures 79-90, see below) was selected for each IspS variant for further study. According to the manufacturer's scheme, will Mu.l of each plasmid was transformed into BL21 (lambda DE3) pLysS (Invitrogen). Transformants were selected on LB medium containing Kan50+ Cm35 and incubated overnight at 37 ℃. The resulting strains were used to express and purify various IspS enzymes for crystallographic studies.

The construction and purification of the amino-terminal 6 His-tagged IspS plasmid, strain are described in example 11.

TABLE 15-2 primers

MCM219	caccatgcgttgtagcgtgtcca(SEQ ID NO：114)
		MCM182	gggcccgtttaaactttaactagactctgcagttagcgttcaaacggcagaa(SEQ ID NO：115)
MCM218	caccatgcgtcgttctgcgaactac(SEQ ID NO：116)

TABLE 15-3 plasmids

TABLE 15-4 strains

Digestion of TEV (tobacco etch Virus) or EK (Enterokinase) -labeled enzymes

TEV cleavage (IspS from strains MD09-165 and MD 09-167)

Strains MD09-165 and MD09-167 are described in example 11. For digestion, the enzyme was purified by means of Ni-charged sepharose (GE Healthcare) and desalted in 50mM HEPES, 50mM NaCl pH 7.4 buffer containing 1mM DTT. Digestion was performed with TurboTEV protease from Eton Bioscience Inc. One unit of TurboTEV was used per 10. mu.g of purified protein. Digestion was performed overnight at 4 ℃. The sample was passed through another Ni column equilibrated in Ni buffer to remove uncleaved enzyme, label, TurboTEV protease (which is also labeled), and impurities. And the Ni column permeate and wash were analyzed using SDS-PAGE gels (NUPAGE, Invitrogen) and DMAPP activity assay. Samples containing pure enzyme were pooled and desalted in 50mM NaCl pH 7.4 buffer containing 1mM DTT and stored at-80 ℃.

EK cleavage (IspS from strains MD08-102 and MD 08-104)

For digestion, the enzyme was purified by Ni-charged sepharose (GE Healthcare) and desalted in 50mM HEPES, 50mM NaCl pH7.4 buffer containing 1mM DTT.

One unit of EKMax was used per 20 μ g of purified protein and digestion was performed overnight at 4 ℃ with EKMax (E180-02) (Invitrogen). The samples were passed through EK Away resin (Invitrogen) to remove excess enterokinase. Samples were loaded in portions onto Ni-loaded Sepharose resin (equilibrated in Ni wash buffer) and incubated for 30 min at 4 ℃ with occasional mixing by inversion. This removes uncleaved enzyme, label and impurities. And the Ni column permeate and wash were analyzed using SDS-PAGE gels (4-12% NUPAGE, Invitrogen) and DMAPP activity assay. Samples containing pure enzyme were pooled and desalted in 50mM HEPES, 50mM NaCl pH7.4 buffer containing 1mM DTT and stored at-80 ℃.

Purification of MBP-IspS

The construction of pMAL-C4X Kudzu for expression of MBP-Kudzu isoprene synthase is described above. MBP-kudzu isoprene synthase was produced on a 15-L scale from batch-cultured E.coli.

Culture medium formula (fermentation medium per liter)

K₂HPO₄7.5g，MgSO₄*7H₂O2 g, citric acid monohydrate 2g, ferrous ammonium citrate 0.3g, yeast extract 0.5g, 1000 times modified trace metal solution 1 ml. All components are added together and dissolved in diH₂And (4) in O. The solution was autoclaved. The pH was adjusted to 7.0 with ammonium hydroxide (30%) and the volume was made up. After sterilization and pH adjustment 10g glucose, thiamine HCl 0.1g and antibiotics were added.

1000 x improved trace metal solution

Citric acid H₂O 40g，MnSO₄*H₂O 30g，NaCl 10g，FeSO₄*7H₂O 1g，CoCl₂*6H₂O 1g，ZnSO₄*7H₂O 1g，CuSO₄*5H₂O 100mg，H₃BO₃ 100mg，NaMoO₄*2H₂O100 mg. Each component is dissolved in diH one time₂In O, the pH is adjusted to 3.0 with HCl/NaOH, then made up to volume and filter sterilized with a 0.22 μm filter.

Fermentation was performed in a 15-L bioreactor using BL21(DE3) E.coli cells containing the pMAL-C4X plasmid expressing Maltose Binding Protein (MBP) -pueraria isoprene synthase fusion molecule. This experiment was performed to produce isoprene synthase at the desired fermentation pH of 7.0 and temperature of 30 ℃. One vial of frozen E.coli strain was thawed and inoculated into tryptone-yeast extract medium. Inoculum was grown to 550nm (OD)₅₅₀) After measuring OD 1.0, 120mL was used to inoculate a 15-L bioreactor, with an initial volume of 9-L.

By adding isopropyl-beta-D-1-thiogalactopyranoside (IPTG) expression of the desired molecule is achieved. When OD is reached₅₅₀When a value of 10 is reached, the IPTG concentration is brought to 1 mM. Cells containing the desired product were harvested 3 hours after IPTG addition.

MBP-IspS purification

The culture broth was centrifuged at 10000Xg for 15 minutes. The precipitate was collected and frozen at-80 ℃ until further purification. Cells were resuspended in MBP binding buffer (5% glycerol, 20mM Tris pH 7.4, 200mM NaCl, 2mM DTT, 1mg/ml lysozyme) and passed 3 times through a 20000psi French press. The lysate was then ultracentrifuged at 100000x g for 1 hour to produce a relatively clear solution. The supernatant was aspirated from the top of the tube without disturbing the gel-like material on the bottom of the centrifuge tube. The supernatant was gel filtered using a Superdex-20026/60 column (GE healthcare). The column was developed at 23 ℃ using MBP binding buffer at a flow rate of 3 mL/min. The fractions were tested for DMAPP activity as described below. Active fractions were pooled and loaded onto 25mL amylose resin (New England Biolabs). The column was washed with 10 column volumes of MBP binding buffer and the protein was subsequently eluted with 2 column volumes of MBP binding buffer containing 10mM maltose to yield more than 90% pure MBP-IspS.

DMAPP assay

The following reaction mixture was used for the DMAPP assay: 25 μ L lysis mixture, 5 μ L MgCl₂(1M), 5. mu.L DMAPP (100mM) and 65. mu.L 100mM Tris pH 8, 100mM NaCl in a total volume of 100. mu.L. The reaction was carried out at 30 ℃ for 15 minutes in a gas tight 1.8mL GC tube. The reaction was stopped by the addition of 100. mu.L of 500mM EDTA (pH 8). The amount of isoprene produced was measured by GC/MS as described above.

Example 16

Three-dimensional Structure of IspS

7 constructs of plant isoprene synthase (IspS) were prepared to generate crystals suitable for X-ray diffraction. These constructs were: constructs containing amino-terminal histidine-tagged maltose binding protein and geum IspS (MBP-geum), full-length Populus alba IspS with amino-terminal histidine-tag (MD08-99), Populus alba IspS with the first 19 amino-terminal residues removed (MD08-100), which constructs also had the amino-terminal His tag removed after purification. Full-length, unlabeled Populus alba IspS (strain RM 11608-2). A truncated populus alba IspS construct (MD09-167) was generated featuring two additional residues before the twin arginine motif. An N.trichocarpa IspS was generated containing an amino-terminal His tag and an amino-terminal truncation (MD08-104) and another construct consisting of IspS from Populus tremuloides with an amino-terminal His tag and an amino-terminal truncation was generated (MD 08-102). The construction of strains expressing various isoprene synthases was described above.

Each construct was purified and then concentrated protein solutions were prepared for investigation of possible crystallization conditions. Each construct was purified and investigated independently as described below. A hanging drop vapor diffusion method was used to establish an all-in-one crystallization screening method. At a minimum, each construct was investigated using the following commercial screening method: crystal screening from Hampton Research (Aliso Viejo, CA) and JCSG + Suite from Qiagen (Valencia, CA).

Purified MBP-pueraria was produced using the following commercial screening method: crystal screening from Hampton Research and JCSG + Suite from Qiagen (Valencia, CA). Additionally, purified MBP-kudzu was sent to Hauptman-woody Institute (Buffalo, NY) for high throughput screening, where not less than 1536 conditions were investigated. The purified MBP-pueraria fusion protein precipitated from solution under most conditions and no protein crystals were observed.

The next construct used for the crystallization screening method was MD08-99 (full length populus alba IspS with an amino terminal histidine-tag). MD08-99 was purified and the histidine tag was removed. The same 3 primary crystallization screens were performed as for MBP-kudzu. Hampton Research crystal screening and Qiagen JCSG + Suite were each performed at multiple protein concentrations. Small needle-like crystals were observed under some Hampton Research crystal screening conditions. Further attempts to improve the crystals involved co-crystallization with the IspS inhibitor ibandronate sodium (Sigma-Aldrich, St Louis, Mo.). In summary, an additional 288 crystallization conditions were attempted with varying pH, concentration and crystallization reagents. The 9 best crystals were then prepared for data collection and tested internally on a Rigaku RU200 rotating anode generator and R-AXIS IV + + and they did not diffract X-rays or salt crystals.

The first 19 amino-terminal residues of the aspen IspS were removed to generate the construct MD 08-100. The construct was purified and the amino-terminal His tag removed. Internal screening was performed using Hampton Research crystal screening and Qiagen JCSG + Suite, each with multiple protein concentrations. Preliminary crystal hits include diffraction to using an internal X-ray generatorHexagonal plate of resolution and diffract toSmall rods of resolution. In an attempt to modify the crystals, MD08-100 co-crystallized with ibandronate sodium or sodium pyrophosphate (Sigma-Aldrich, St Louis, MO), both of which were inhibitors of IspS activity. Neither inhibitor produces improved crystallinity or improved diffraction. An additional 168 crystallization conditions were attempted with varying pH, concentration and crystallization reagents. The 21 most promising crystals of MD08-100 were screened for diffraction, the best resolution obtained being

Full-length, unlabeled Populus alba IspS (strain RM11608-2) was purified from the fermentation process. A preliminary screen was set up using Hampton Research crystal screening and crystals were observed under 4 different conditions. All 4 crystals were tested internally for diffraction, 3 crystals were salt crystals and one did not diffract.

A truncated populus alba IspS construct (MD09-167) was generated featuring two additional residues before the twin arginine motif. The construct contains a carboxy-terminal histidine tag and crystallization experiments were established with or without cleavage of the tag, at varying protein concentrations and in the presence or absence of sodium pyrophosphate. Preliminary work according to MBP-KudzuvineAnd (5) crystal screening. Crystals from this construct were observed under a number of conditions; 528 variables including pH, precipitation reagent, concentration and inhibitor were optimized. From the optimization experiments, 15 different MD09-167 crystals were screened internally for diffraction. In an effort to improve resolution, various crystal freezing conditions were tested, with the effect of improving diffraction limit being fromThe improvement is that

A new construct containing Populus tomentosa IspS was generated, which contained a histidine-tag and an amino-terminal truncation (MD 08-104). Purified MD08-104, from which the histidine-tag was cleaved, was investigated using Hampton Research crystal screening and Qiagen JCSG + Suite. This construct produced a heavier pellet than the poplar IspS construct. Very small needles were observed and all crystals were not suitable for diffraction.

Another construct consisting of IspS from populus trichocarpa with a histidine-tag and amino-terminal truncation was generated (MD 08-102). Purified MD08-102 with or without excision of the histidine-tag was established at different protein concentrations using Hampton Research crystal screening and qiagen jcsg + Suite. Rod-like and plate-like crystals were observed under some conditions and an additional 120 experiments were performed to improve the crystals by varying pH, concentration and crystallization reagents. From the optimization experiment, 10 crystals were tested internally, and the initial best diffraction achieved that upon further adjustment of the freezing conditions of the crystals, diffraction from the protein without excision of the histidine tag was found to The crystal of (4). By mixing 2. mu.g of protein (10mg/ml, containing 30mM MgCl)₂) With 2. mu.L of precipitant solution [ 10% (wt/vol) polyethylene glycol 8000, 0.1M HEPES, pH 7.5, 8% ethylene glycol]The crystals were mixed and equilibrated with 500. mu.L of precipitant to grow. A cluster of rod-shaped crystals appeared after 3 weeks. The crystal belongs to a squareSpace group P43212 and has a unit cell size: 154.2, 154.2 and 142.7.

Internal X-ray diffraction data were collected using a Rigaku RU200 generator and an R-AXIS IV + + detector at 100K under a nitrogen stream. Prior to rapid freezing of the crystals in liquid nitrogen, the crystals were cryoprotected by rapidly passing the crystals through a solution containing 10% (wt/vol) polyethylene glycol 8000, 0.1M HEPES, pH 7.5 and 25% ethylene glycol. Data were integrated using Mosflm (Leslie, A. (1998) J. of application. Crystagonography 30, 1036-. Followed by MrBUMP Keegan, R.M. and Winn, M.D. (2007) Acta Crystagonococca Section D63, 447-; vagin, A. and Teplyakov, A. (1997) J.of appl.Crystallography 30, 1022-1025), data were phased by molecular replacement methods with the monomer of the limonene synthase (protein database ID 2ONH) (Berman, H., et al (2007) Nucl. acids Res.35, D301-303) as the starting model. The crystals contained one dimer in the asymmetric unit with a solvent content of 66%.

Subsequent collection of crystals from the same crystals using Stenford synchrotron radiation laboratory beam stream line 11-1A data set. These data were also processed using Mosflm and SCALA. The data set and revised statistics are given in Table 16-1.

The iterative manual reconstruction procedure was used with the visualization program Coot (Emsley, p. and Cowtan, K. (2004) Acta Crystallographica Section D60, 2126-. During the correction, the geometry of the protein was checked using Molprobity (Davis, i.w., et al (2007) nuclear acids res., gkm 216).

The folding of poplar IspS is similar to that of borneol-based diphosphate synthase (Whittington, D.A., et al (2002) Proc.Natl Acad.Sci.USA 99, 15375-. The structure consists of two helical domains, a carboxy-terminal domain containing the active site and an amino-terminal domain (FIGS. 90 and 91). The coordinates are provided in tables 16-7.

TABLE 16-1 data Collection and modified statistics

Flexible ring

A unique and unexpected finding from the determination of the three-dimensional structure of isoprene synthase is that several key loops forming the active site are flexible. This finding was immediately seen when the known structures of other terpene synthases were compared with those of isoprene synthase (FIG. 94). In general, the structure is highly conserved in secondary structure and conformation of the connecting loops. (in this example of aspen IspS from construct p.tremtrc-pET200, the numbering convention is such that the first number containing the complete sequence of the tag is-35 and the first residue of IspS is 1). However, it was observed that the three segments forming the largest part of the substrate binding pocket, in particular the truncated amino-terminus, differed along the 2 loops consisting of residues 438-. This has been attributed to the lack of substrate complexed with this enzyme in our structural assays.

For example, comparing this enzyme to BdpS, we found that the loops corresponding to residues 498-513 and 573-587 consist of the same number of residues and have homologous but non-identical amino acid sequences in these regions. We expect that as these structures are more thoroughly studied, it will be found that the relevant terpene synthases exhibit similar flexibility within the segment. The residues corresponding to these variable loop regions in terpene synthases are listed in Table 16-2.

TABLE 16-2 residues corresponding to the variable loop region in terpene synthases

	Populus IspS	LS	BdpS	TEAS
					Amino terminus I	Met 1	Met 57	Ile 54	Val 14
	Arg 2	Arg 58	Arg 55	Arg 15
						Arg 3	Arg 59	Arg 56	Pro 16
	Ser 4	Ser 60	Ser 57	Val 17
						Ala 5	Gly 61	Gly 58	Ala 18
	Asn 6	Asn 62	Asn 59	Asp 19
						Tyr 7	Tyr 63	Tyr 60	Phe 20
	Glu 8	Asn 64	Gln 61	Ser 21
						Pro 9	Pro 65	Pro 62	Pro 22
	Asn 10	Ser 66	Ala 63	Ser 23
						Ser 11	Arg 67	Leu 64	Leu 24
	Trp 12	Trp 68	Trp 65	Trp 25
						Asp 13	Asp 69	Asp 66	Gly 26
	Tyr 14	Val 70	Ser 67	Asp 27
						Asp 15	Asn 71	Asn 68	Gln 28
	Tyr16	Phe 72	Tyr 69	Phe 29

Amino terminus II	Leu 17	Ile 73	Ile 70	Leu 30
						Leu 18	Gln 74	Gln 71	Ser 31
	Ser 19	Ser 75	Ser 72	Phe 32
						Ser 20	Leu 76	Leu 73	Ser 34
	Asp 21	Leu 77	Asn 74	Ile 35

	Thr 22	Ser 78	Thr 75	Asp 36
					Asp 23	Asp 79	Pro 76	Asn 37
	Glu 24	Tyr 80	Tyr 77	Gln 38
					Ser 25	Lys 81	Thr 78	Val 39
	Ile 26	Glu 82	Glu 79	Ala 40
					Glu 27	Asp 83	Glu 80	Glu 41
	Val 28	Lys 84	Arg 81	Lys 42

Ring I	Leu 438	Leu 498	Leu 498	Thr 446
					Ala 439	Gly 499	Gly 499	Ala 447
	Ser 440	Thr 500	Thr 500	The 448
					Ala 441	Ser 501	Ser 502	Tyr 449
	Ser 442	Val 502	Tyr 503	Glu 450
					Ala 443	Glu 503	Phe 504	Val 451
	Glu 444	Glu 504	Glu 505	Glu 452
					Ile 445	Val 505	Leu 506	Lys 453
	Ala 446	Ser 506	Ala 507	Ser 454
					Arg 447	Arg 507	Arg 508	Arg 455
	Gly 448	Gly 508	Gly 509	Gly 456
					Glu 449	Asp 509	Asp 510	Gln 457
	Thr 450	Val 510	Val 511	Ile 458
					Ala 451	Pro 511	Pro 512	Ala 459
	Asn 452	Lys 512	Lys513	Thr 460
					Ser 453	Ser 513	Thr 514	Gly 461

Ring II	Tyr 512	Tyr 576	Tyr 573	Tyr 520
								Ile 521
	His 513	His 577	Leu 574	His 522
					Asn 514	Asn 578	His 575	Asn 523
	Gly 515	Gly 579	Gly 576	Leu 524
					Asp 516	Asp 580	Asp 577	Asp 525
	Ala 517	Gly 581	Gly 578	Gly 526
					His 518	His 582	Phe 579	Tyr 527
	Thr 519	Gly 583	Gly 580	The 528
					Ser 520	Thr 584	Val 581	His 529
	Pro 521	Gln 585	Gln 582	Pro 530
					Asp 522	His 585	His 583	Glu 531
	Glu 523	Pro 586	Ser 584	Lys 532
					Leu 524	Ile 587	Lys 585	Val 533
	Thr 525	Ile 588	Thr 586	Lue 534
					Arg 526	His 589	Tyr 587	Lys 535

This important finding can be used to engineer improved isoprene synthases in a straightforward manner. What is desired would be: the enzyme performance was enhanced using this flexibility as follows: substitutions are made in the amino acids forming these segments to facilitate the transition that the enzyme must undergo during the step of binding the substrate, and to allow rearrangement of the substrate in different kinetic steps (presumably occurring during enzymatic dephosphorylation), and to allow electron transfer to convert DMAPP to isoprene.

This structure provides a new perspective: these loops can exist in at least 2 conformations: an "open" form in the absence of substrate, as we have seen in the uncomplexed structure of isoprene synthase, and a "closed" or active form when bound to a substrate. Thus, it would also be beneficial to modify residues as described in tables 16-3 that contact the active form of the ring.

TABLE 16-3 residues into the 5 Angstrom range of the flexible element

Selection of sites for improving plant isoprene synthase

Plant isoprene synthase is expected to be homologous to terpene synthase. The three-dimensional structure of 3 homologous terpene synthases has been determined: salvia officinalis (Salvia officinalis) borneol-based diphosphate synthase (BdpS; pdb entry 1N1B), spearmint (Mentha spicata) limonene synthase (LS; pdb entry 2ONG) and tobacco 5-epi-aristolocene synthase (TEAS; pdb entry 5 EAS). These enzymes share only 33% homology, but their tertiary structure is conserved. Sequence identity is shown in Table 16-4 and structural homology between these structures is shown in Table 16-5. Furthermore, the structure of the intermediate complex with all 3 related enzymes indicates that both the tertiary folding and the specific interactions in the active sites of these enzymes are highly conserved.

TABLE 16-4 percent identity of terpene cyclase

	Populus deltoides IspS	1N1B	2ONG	5EAS^e
					Populus alba IspS^a	98.6	40.7	41.3	33.2
Populus deltoides IspS^b		41.0	41.4	33.2
					1N1B^c			51.4	33.8
2ONG^d				33.3

^aPopulus alba isoprene synthase

^bPopulus tremuloides isoprene synthase

^cBorneol-based diphosphate synthase

^dLimonene synthase

^e5-epi-aristolocene synthase

TABLE 16-5 structural alignment of terpene synthases

	1N1B^b	20NG^c	5EAS^d
				Populus deltoides IspS^a	1.40(465)^e	1.29(468)	1.62(458)

1N1B		1.27(520)	1.97(476)
				20NG			1.83(477)

^aPopulus tremuloides isoprene synthase

^bBorneol-based diphosphate synthase

^cLimonene synthase

^d5-epi-aristolocene synthase

^eRoot mean square deviation of C.alpha.atomThe number of residues aligned is shown in parentheses

In this example of aspen IspS from construct p.tremtrc-pET200, the numbering convention is such that the first number containing the complete sequence of the tag is-35 and the first residue of IspS is 1.

Comparison of active sites from the BdpS and poplar IspS structures indicates that the active sites involved in metal ion binding and phosphate recognition are conserved. In particular, Arg 255, Asp 292, Asp 296, Glu 370, Arg 433 and Asn 436 of poplar IspS were observed to overlap with equivalent residues in BdpS. The position of the intermediate of BdpS was also compared to the poplar IspS structure. Based on this comparison, it was possible to identify similar binding regions and proximity directions required for dimethylallyl pyrophosphate to bind and react with the poplar IspS enzyme.

Based on the structure of the poplar IspS, sites in the poplar IspS were identified as mutagenic candidates to generate variant IspS enzymes with improved performance. Briefly, IspS select sites that may alter metal binding, diphosphate recognition, DMAPP strand binding and/or near-active site interactions.

I. Diphosphate/metal binding sites

The side chains of amino acid residues in the poplar IspS near the metal and diphosphate binding sites were identified. These residues include Asp 293, Tyr 385, Ser 392 and Asp 437. Engineering of these sites can result in increased enzymatic activity.

Substrate proximity Ring

The substrate of the poplar IspS was located close to the loop in a region facing away from the BdpS structure. In the BdpS structure, the residue creates a cap over the active site. It is likely that the structure of poplar IspS will form a similar structure once the substrates are bound. Likewise, the residues in these loops (including residues 440-453 and 512-524) may be in positions that alter the activity of the poplar IspS. In the poplar IspS enzyme, residues 440-453 have the sequence SASAEIARGETANS and residues 512-526 have the sequence YHNGDAHTSPDEL.

Prenyl binding sites

The complex of BdpS and the reaction product camphylene diphosphate (PDB entry 1N24) was used to identify residues in the poplar IspS structure that could be used to modulate substrate specificity and/or reaction rate (rate of altered substrate and product binding and removal) by means of protein engineering. These residues include Ser 261, Trp 264, Phe 285, Thr 289, Ser 393, Ser 394, Phe 432, and Try 512.

TABLE 16-6 candidate mutagenesis sites

	Populus IspS
		DPP/Metal binding site	Asp 293

	Tyr 385
			Ser 392
	Asp 437

Substrate proximity loop I	Ser 440
			Ala 441
	Ser 442
			Ala 443
	Glu 444
			Ile 445
	Ala 446
			Arg 447
	Gly 448
			Glu 449
	Thr 450
			Ala 451
	Asn 452
			Ser 453

		Substrate proximity loop II	Tyr 512
	His 513
			Asn 514
	Gly 515
			Asp 516
	Ala 517

	His 518
		Thr 519
	Ser 520
		Pro 521
	Asp 522
		Glu 523
	Leu 524

Prenyl binding sites	Ser 261
		Trp 264
	Phe 285
		Thr 289
	Ser 393
		Ser 394
	Phe 432
		Tyr 512

TABLE 16-7. coordinates of Populus tremuloides

The title- - - -XX-XXX-XXXXxx

COMPND ---

Note 3

Note 3 correction.

Note 3 program: REFMAC 5.5.0088

Note 3 author: MURSHUDOV, VAGIN, DODSON

Note 3

Note 3 correction object: maximum likelihood

Note 3

Note 3 data used in the correction.

Note 3 high resolution (angstroms): 3.05

Note 3 low resolution (angstroms): 110.17

Note 3 data cutoff (sigma (f)): is free of

Note 3 integrity (%) of range: 99.67

Note 3 number of reflections: 32446

Note 3

Note 3 that the data used in the fitting correction.

Note 3 cross-validation method: THROUGHOUT

Note 3 free R-value check setting selection: random

Note 3R values (work + check set): .21396

Note 3R values (working settings): .21092

Note 3 free R values: .27112

Note 3 free R value check set size (%): 5.1

Note 3 free R value check set count: 1727

Note 3

Note 3 fitting in highest resolution BIN

Total number of BINs used for note 3: 20

Note 3 BIN high resolution: 3.050

Note 3 BIN low resolution: 3.129

Note 3 BIN reflection (working settings): 2359

Note 3 BIN integrity (work + test) (%): 100.00

Note 3 BIN R values (working settings): .288

Note 3 BIN free R value SET COUNT: 127

Note 3 BIN free R values: .352

Note 3

Note 3 the number of non-hydrogen atoms used in the correction.

Note 3 all atoms: 8349

Note 3

Note the 3B values.

Note 3 is from the WILSON curve (A)^**2)：NULL

Note 3 mean B value (Total A)^**2)：24.592

Note 3 Total anisotropy B values.

Note 3B 11 (A)^**2)：.41

Note 3B 22 (A)^**2)：.41

Note 3B 33 (A)^**2)：-.81

Note 3B 12 (A)^**2)：.00

Note 3B 13 (A) ^**2)：.00

Note 3B 23 (A)^**2)：.00

Note 3

Note 3 the estimated overall coordinate error.

Note 3 esu (a) based on R value: NULL

Note 3 is based on the free R value esu (a): .427

Note 3 based on the most probable esu (a): .327

Note 3 ESU (A) based on the most probable B value^**2)：39.836

Note 3

The correlation coefficient is annotated 3.

Note 3 correlation coefficient FO-FC: .916

Note 3 correlation coefficient FO-FC FREE: .868

Note 3

Note 3 RMS deviation COUNT RMS WEIGHT from ideal

Note 3 bond length of the modified atom (a): 8495; 011; .022

Note 3 other bond length (a): 5804; 001; .020

Note 3 bond angle (degree) of the modified atom: 11476, respectively; 1.279; 1.953

Note 3 other bond angles (degrees): 14093, respectively; 882; 3.000

Note 3 torsion angle, PERIOD 1 (degrees): 1020; 7.002, respectively; 5.000

Note 3 torsion angle, PERIOD 2 (degrees): 435; 35.412, respectively; 24.299

Note 3 torsion angle, PERIOD 3 (degrees): 1525, adding a stabilizer to the mixture; 18.250, respectively; 15.000

Note 3 torsion angle, PERIOD 4 (degrees): 58; 16.811, respectively; 15.000

Note 3 chiral center correction (A)^**3)：1266；.070；.200

Note 3 correction atom of total plane (a): 9416; 005; .020

Note 3 general plane other (a): 1780; 001; .020

Note 3

Note 3 Isotropic thermal factor Limit COUNT RMS weight

Note 3 ownerChain-bond modified atoms (A)^**2)：5104；.514；1.500

Note 3 other atoms of the main chain bond (A)^**2)：2068；.059；1.500

Note 3 Main chain Angle-corrected atom (A)^**2)：8204；1.000；2.000

Note 3 atoms with side chain bond modifications (A)^**2)：3391；1.218；3.000

Note 3 side chain Angle corrected atom (A)^**2)：3272；2.157；4.500

Note 3

Note 3 NCS constraint statistics

Note 3 number of different NCS groups: 1

Note 3

Note 3 NCS population number: 1

Note 3 number of chains: a B

Note 3 number of component NCS groups: 1

Note 3 COMPONENT C SSSEQI TO C SSSEQI CODE

Note 31A 17A 5416

Note 31B 17B 5416

Note 3 GROUP CHAIN COUNT RMS WEIGHT

Note 3 LOOSE POSITIONAL 11 (A): 7038; 37; 5.00

Note 3 LOOSE THERMAL 11 (A)^**2)： 7038； 1.09；10.00

Note 3

Note 3 TWIN details

Note 3 number of twin domains: NULL

Note 3

Note 3 TLS details

Note number of 3 TLS groups: 8

Note that the atoms recorded in 3 contain only residual B coefficients

Note 3

Note 3 TLS group: 1

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: A17A 219

Note 3 group origin (a): -64.766737.6643-.0896

Annotating 3T tensors

Note 3T 11: 0648T 22: .0357

Note 3T 33: 0787T 12: .0200

Note 3T 13: 0129T 23: -.0089

Annotating 3L tensors

Note 3L 11: 3.7204L 22: 1.5111

Note 3L 33: 2.6701L 12: .5715

Note 3L 13: 6692L 23: -.9699

Annotating 3S tensors

Note 3S 11: 0562S 12: 0478S 13: -.1976

Note 3S 21: 1702S 22: 0055S 23: .1376

Note 3S 31: 0900S 32: 2188S 33: -.0507

Note 3

Note 3 TLS group: 2

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: A220A 287

Note 3 group origin (a): -59.57878.4529-.7693

Annotating 3T tensors

Note 3T 11: 1615T 22: .0645

Note 3T 33: 1539T 12: -.0314

Note 3T 13: 0461T 23: .0198

Annotating 3L tensors

Note 3L 11: 2.4192L 22: 4.6709

Note 3L 33: 7709L 12: -3.2943

Note 3L 13: -. 1814L 23: -.0705

Annotating 3S tensors

Note 3S 11: 0055S 12: 0699S 13: -.2073

Note 3S 21: 1805S 22: 0996S 23: .3781

Note 3S 31: 2596S 32: 0887S 33: -.1051

Note 3

Note 3 TLS group: 3

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: A288A 374

Note 3 group origin (a): -40.18661.6932.5805

Annotating 3T tensors

Note 3T 11: 1149T 22: .1003

Note 3T 33: 1629T 12: .0153

Note 3T 13: 0224T 23: .0164

Annotating 3L tensors

Note 3L 11: 2271L 22: .7399

Note 3L 33: 4.8529L 12: .3413

Note 3L 13: 4755L 23: -.1746

Annotating 3S tensors

Note 3S 11: 0449S 12: 0288S 13: -.1131

Note 3S 21: 1346S 22: 0665S 23: -.2749

Note 3S 31: 0040S 32: 1558S 33: .1114

Note 3

Note 3 TLS group: 4

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: A375A 541

Note 3 group origin (a): -47.222021.53996.9217

Annotating 3T tensors

Note 3T 11: 1551T 22: .1194

Note 3T 33: 1485T 12: -.0666

Note 3T 13: 0275T 23: .0272

Annotating 3L tensors

Note 3L 11: 2.2352L 22: 2.1698

Note 3L 33: 2.3370L 12: -.4501

Note 3L 13: 2.2662L 23: -.1852

Annotating 3S tensors

Note 3S 11: 0233S 12: 3041S 13: -.0323

Note 3S 21: 3375S 22: 0236S 23: .0121

Note 3S 31: 0592S 32: 2979S 33: -.0469

Note 3

Note 3 TLS group: 5

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: B17B 219

Note 3 group origin (a): -73.9834-39.9016-18.5783

Annotating 3T tensors

Note 3T 11: 0658T 22: .1153

Note 3T 33: 1251T 12: -.0621

Note 3T 13: 0164T 23: -.0098

Annotating 3L tensors

Note 3L 11: 4.6230L 22: 1.7260

Note 3L 33: 3.8816L 12: -.4202

Note 3L 13: -1.8646L 23: -.9046

Annotating 3S tensors

Note 3S 11: 0685S 12: 0375S 13: -.0003

Note 3S 21: 1931S 22: 0510S 23: -.0097

Note 3S 31: 0317S 32: 2047S 33: .0175

Note 3

Note 3 TLS group: 6

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: B220B 287

Note 3 group origin (a): -62.1586-12.7634-18.1912

Annotating 3T tensors

Note 3T 11: 1825T 22: .0804

Note 3T 33: 1512T 12: .0549

Note 3T 13: 0773T 23: .0208

Annotating 3L tensors

Note 3L 11: 5.4421L 22: 4.0606

Note 3L 33: 1.5369L 12: 4.6706

Note 3L 13: -2.0058L 23: -1.5537

Annotating 3S tensors

Note 3S 11: 1622S 12: 0431S 13: .3257

Note 3S 21: 1755S 22: 0292S 23: .2977

Note 3S 31: 1910S 32: 0506S 33: -.1914

Note 3

Note 3 TLS group: 7

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: B288B 374

Note 3 group origin (a): -41.6930-10.8250-19.6636

Annotating 3T tensors

Note 3T 11: 1424T 22: .0604

Note 3T 33: 1153T 12: .0184

Note 3T 13: 0146T 23: .0276

Annotating 3L tensors

Note 3L 11: 6426L 22: .8163

Note 3L 33: 2.3437L 12: -.1831

Note 3L 13: 5246L 23: .4917

Annotating 3S tensors

Note 3S 11: 0592S 12: 0206S 13: .0071

Note 3S 21: 0906S 22: 0229S 23: -.1585

Note 3S 31: 0355S 32: 0262S 33: -.0363

Note 3

Note 3 TLS group: 8

Note 3 number of component groups: 1

Note 3 component C SSSEQI TO C SSSEQI

Note 3 residue range: B375B 541

Note 3 group origin (a): -53.4886-28.3212-26.0670

Annotating 3T tensors

Note 3T 11: 1107T 22: .1220

Note 3T 33: 1514T 12: .0692

Note 3T 13: -. 0073T 23: .0518

Annotating 3L tensors

Note 3L 11: 2.6766L 22: 1.8433

Note 3L 33: 2.6389L 12: .1130

Note 3L 13: -2.4696L 23: .6986

Annotating 3S tensors

Note 3S 11: 1115S 12: 3882S 13: .0569

Note 3S 21: 0725S 22: 0724S 23: .1450

Note 3S 31: 1453S 32: 4044S 33: -.0392

Note 3

Note 3 bulk solvent modeling.

Note 3 the method used: MASK

Note the parameters of the 3 MASK calculation

Note 3 VDW probe radius: 1.40

Note 3 ion probe radius: .80

Note 3 shrink radius: .80

Note 3

Note 3 other correction flags:

note 3 that hydrogen has been added in lattice position

Note the 3U value: only residue of

Note 3

CISPEP 1 ALA A 446 ARG A 447 .00

CISPEP 2 GLY A 515 ASP A 516 .00

CISPEP 3 THR B 22 ASP B 23 .00

CISPEP 4 ALA B 446 ARG B 447 .00

CISPEP 5 GLY B 515 ASP B 516 .00

CRYST1 155.800 155.800 143.690 90.00 90.00 90.00 P 43 21 2

SCALE1 .006418 .000000 .000000 .00000

SCALE2 .000000 .006418 .000000 .00000

SCALE3 .000000 .000000 .006959 .00000

Atom 1N LEU A17-63.93024.416-19.2021.0030.90N

Atom 2 CA LEU A17-64.13223.019-19.7311.0031.43C

Atom 4 CB LEU A17-63.30822.800-21.0211.0031.35C

Atom 7 CG LEU A17-64.00223.016-22.3861.0031.95C

Atom 9 CD1 LEU A17-62.98923.068-23.5501.0031.88C

Atom 13 CD2 LEU A17-65.05221.915-22.6761.0031.95C

Atom 17C LEU A17-63.78321.952-18.6601.0031.39C

Atom 18O LEU A17-63.14222.291-17.6511.0031.61O

Atom 22N LEU A18-64.21620.693-18.8771.0031.11N

Atom 23 CA LEU A18-63.98619.529-17.9571.0030.78C

Atom 25 CB LEU A18-62.50319.072-17.9351.0030.97C

Atom 28 CG LEU A18-61.30319.949-17.4961.0031.10C

Atom 30 CD1 LEU A18-61.40620.430-16.0641.0030.71C

Atom 34 CD2 LEU A18-59.97719.173-17.7031.0031.87C

Atoms 38C LEU A18-64.53119.665-16.5221.0030.38C

Atom 39O LEU A18-64.83718.667-15.8831.0029.86O

Atom 41N SER A19-64.58720.900-16.0231.0030.45N

Atom 42 CA SER A19-65.33521.276-14.8151.0030.37C

Atom 44 CB SER A19-64.60422.417-14.0261.0030.02C

Atom 47 OG SER A19-64.88123.741-14.4891.0028.00O

Atom 49C SER A19-66.78421.654-15.2181.0031.03C

Atom 50O SER A19-67.66621.711-14.3671.0030.95O

Atom 52N SER A20-67.02321.880-16.5191.0031.85N

Atom 53 CA SER A20-68.35522.247-17.0511.0032.37C

Atom 55 CB SER A20-68.29122.507-18.5791.0032.39C

Atom 58 OG SER A20-67.38723.542-18.9311.0031.77O

Atom 60C SER A20-69.35721.124-16.7441.0033.04C

Atom 61O SER A20-69.07620.254-15.9221.0033.08O

Atom 63N ASP A21-70.52221.136-17.3931.0033.88N

Atom 64 CA ASP A21-71.51220.069-17.2061.0034.48C

Atom 66 CB ASP A21-72.90720.655-17.1271.0034.59C

Atom 69 CG ASP A21-73.02221.661-16.0061.0035.54C

Atom 70 OD1 ASP A21-72.04121.836-15.2511.0035.31O

Atom 71 OD2 ASP A21-74.08222.289-15.8701.0038.72O

Atom 72C ASP A21-71.40918.975-18.2601.0034.94C

Atom 73O ASP A21-72.13418.947-19.2691.0034.58O

Atom 75N THR A22-70.45718.086-17.9891.0035.66N

Atom 76 CA THR A22-70.34016.799-18.6571.0036.27C

Atom 78 CB THR A22-68.89516.576-19.1681.0036.30C

Atom 80 OG1 THR A22-67.96817.278-18.3221.0036.04O

Atom 82 CG2 THR A22-68.75517.088-20.6041.0036.11C

Atom 86C THR A22-70.79215.714-17.6481.0036.83C

Atom 87O THR A22-69.96815.022-17.0351.0037.05O

Atom 89N ASP A23-72.12115.599-17.4941.0037.27N

Atom 90 CA ASP A23-72.79014.802-16.4411.0037.25C

Atom 92 CB ASP A23-72.96215.659-15.1671.0037.17C

Atom 95 CG ASP A23-71.62516.081-14.5491.0037.74C

Atom 96 OD1 ASP A23-70.71415.241-14.4361.0038.88O

Atom 97 OD2 ASP A23-71.47217.256-14.1641.0038.91O

Atom 98C ASP A23-74.17214.351-16.9561.0037.18C

Atom 99O ASP A23-75.13715.112-16.8461.0037.10O

Atom 101N GLU A24-74.28013.134-17.5011.0037.23N

Atom 102 CA GLU A24-75.40612.815-18.4101.0037.58C

Atom 104 CB GLU A24-74.94113.007-19.8651.0037.77C

Atom 107 CG GLU A24-74.42414.417-20.2391.0037.98C

Atom 110 CD GLU A24-74.12114.556-21.7461.0038.35C

Atom 111 OE1 GLU A24-74.28413.564-22.5031.0038.12O

Atom 112 OE2 GLU A24-73.72115.661-22.1741.0038.18O

Atom 113C GLU A24-76.13911.440-18.3231.0037.79C

Atom 114O GLU A24-77.32311.397-17.9601.0037.90O

Atom 116N SER A25-75.46210.345-18.6961.0037.92N

Atom 117 CA SER A25-76.1409.070-19.0481.0038.09C

Atom 119 CB SER A25-75.1678.076-19.7231.0038.11C

Atom 122 OG SER A25-74.5037.239-18.7871.0038.02O

Atom 124C SER A25-76.9178.374-17.9071.0038.42C

Atom 125O SER A25-76.6358.581-16.7241.0038.15O

Atom 127N ILE A26-77.8617.511-18.3121.0039.00N

Atom 128 CA ILE A26-78.9937.042-17.4761.0039.30C

Atom 130 CB ILE A26-78.5945.965-16.4291.0039.34C

Atom 132 CG1 ILE A26-77.8924.791-17.1201.0039.37C

Atom 135 CD1 ILE A26-77.7663.531-16.2531.0039.46C

Atom 139 CG2 ILE A26-79.8365.423-15.7141.0039.29C

Atom 143C ILE A26-79.7168.260-16.8521.0039.66C

Atom 144O ILE A26-79.2748.831-15.8381.0039.49O

Atom 146N GLU A27-80.8378.623-17.4861.0039.99N

Atom 147 CA GLU A27-81.4509.965-17.3831.0040.11C

Atom 149 CB GLU A27-82.39510.183-18.5871.0040.19C

Atom 152 CG GLU A27-81.63210.311-19.9041.0040.60C

Atom 155 CD GLU A27-82.52810.434-21.1161.0041.06C

Atom 156 OE1 GLU A27-83.3289.502-21.3671.0041.10O

Atom 157 OE2 GLU A27-82.40911.458-21.8301.0041.36O

Atom 158C GLU A27-82.14410.264-16.0421.0040.02C

Atom 159O GLU A27-81.9779.518-15.0711.0040.01O

Atom 161N VAL A28-82.89911.370-16.0051.0039.84N

Atom 162 CA VAL A28-83.46311.960-14.7791.0039.65C

Atom 164 CB VAL A28-83.88410.905-13.6941.0039.78C

Atom 166 CG1 VAL A28-84.47211.596-12.4561.0039.87C

Atom 170 CG2 VAL A28-84.8879.880-14.2741.0039.49C

Atom 174C VAL A28-82.46912.980-14.2061.0039.46C

Atom 175O VAL A28-82.79813.717-13.2701.0039.38O

Atom 177N HIS A29-81.26413.025-14.7861.0039.30N

Atom 178 CA HIS A29-80.23614.006-14.4121.0039.23C

Atom 180 CB HIS A29-78.86613.344-14.1861.0039.45C

Atom 183 CG HIS A29-78.91012.139-13.2961.0041.29C

Atom 184 ND1 HIS A29-78.40712.140-12.0071.0042.51N

Atom 186 CE1 HIS A29-78.58510.942-11.4721.0043.37C

Atom 188 NE2 HIS A29-79.18110.164-12.3651.0043.18N

Atom 190 CD2 HIS A29-79.39310.888-13.5151.0042.55C

Atom 192C HIS A29-80.09015.110-15.4641.0038.60C

Atom 193O HIS A29-79.04915.774-15.4991.0038.61O

Atom 195N LYS A30-81.11015.320-16.3111.0037.87N

Atom 196 CA LYS A30-81.26516.610-17.0011.0037.22C

Atoms 198 CB LYS A30-82.28316.542-18.1401.0037.09C

Atom 201 CG LYS A30-81.76415.794-19.3601.0037.00C

Atom 204 CD LYS A30-82.83115.653-20.4571.0036.89C

Atom 207 CE LYS A30-82.41314.637-21.5311.0036.48C

Atom 210 NZ LYS A30-83.42214.458-22.6111.0035.46N

Atom 214C LYS A30-81.64817.649-15.9381.0036.88C

Atom 215O LYS A30-82.51618.499-16.1361.0036.71O

Atom 217N ASP A31-80.98217.506-14.7881.0036.58N

Atom 218 CA ASP A31-80.89518.476-13.7201.0036.18C

Atom 220 CB ASP A31-80.51817.751-12.3961.0036.20C

Atom 223 CG ASP A31-79.86318.669-11.3421.0036.65C

Atom 224 OD1 ASP A31-80.05519.901-11.3901.0038.17O

Atom 225 OD2 ASP A31-79.14718.150-10.4491.0035.46O

Atom 226C ASP A31-79.81119.426-14.2261.0035.74C

Atom 227O ASP A31-78.62819.279-13.9181.0035.44O

Atom 229N LYS A32-80.22020.343-15.0961.0035.30N

Atom 230 CA LYS A32-79.36021.449-15.5071.0034.69C

Atom 232 CB LYS A32-78.69821.188-16.8491.0034.63C

Atom 235 CG LYS A32-77.69920.042-16.7651.0034.51C

Atom 238 CD LYS A32-76.95319.853-18.0781.0034.48C

Atom 241 CE LYS A32-76.85918.387-18.5031.0033.77C

Atom 244 NZ LYS A32-77.00218.244-19.9851.0032.92N

Atom 248C LYS A32-80.16222.745-15.4591.0034.01C

Atom 249O LYS A32-80.46823.380-16.4731.0033.41O

Atom 251N ALA A33-80.54023.051-14.2191.0033.21N

Atom 252 CA ALA A33-80.78524.381-13.7661.0032.60C

Atom 254 CB ALA A33-81.61924.347-12.4841.0032.28C

Atom 258C ALA A33-79.41125.031-13.5241.0032.31C

Atom 259O ALA A33-79.33526.081-12.9011.0032.80O

Atom 261N LYS A34-78.32324.389-13.9681.0031.70N

Atom 262 CA LYS A34-77.03525.071-14.1861.0031.12C

Atom 264 CB LYS A34-75.86324.089-14.1281.0031.23C

Atom 267 CG LYS A34-75.11824.077-12.7911.0031.76C

Atom 270 CD LYS A34-73.58424.412-12.9211.0031.49C

Atom 273 CE LYS A34-72.68523.269-12.5061.0030.50C

Atom 276 NZ LYS A34-72.95122.090-13.3481.0029.53N

Atom 280C LYS A34-77.02425.884-15.5181.0030.50C

Atom 281O LYS A34-76.97725.353-16.6251.0029.82O

Atom 283N LYS A35-76.92727.191-15.3371.0029.97N

Atom 284 CA LYS A35-77.63228.233-16.0981.0029.41C

Atom 286 CB LYS A35-78.85227.704-16.8671.0029.53C

Atom 289 CG LYS A35-80.16627.594-16.0771.0030.18C

Atom 292 CD LYS A35-81.03028.858-16.2031.0031.25C

Atom 295 CE LYS A35-82.37528.721-15.4861.0031.85C

Atom 298 NZ LYS A35-83.29829.865-15.7831.0031.73N

Atom 302C LYS A35-78.05329.277-15.0261.0028.53C

Atom 303O LYS A35-78.24630.460-15.3071.0028.53O

Atom 305N LEU A36-78.22528.791-13.7961.0027.29N

Atom 306 CA LEU A36-77.99829.576-12.5941.0026.21C

Atom 308 CB LEU A36-78.08828.679-11.3641.0025.76C

Atom 311 CG LEU A36-79.46828.350-10.8321.0024.08C

Atom 313 CD1 LEU A36-79.37627.233-9.8361.0022.16C

Atom 317 CD2 LEU A36-80.05129.586-10.2131.0023.45C

Atoms 321C LEU A36-76.58730.137-12.6651.0025.93C

Atom 322O LEU A36-76.29031.221-12.1371.0026.11O

Atom 324N GLU A37-75.71429.332-13.2601.0025.24N

Atom 325 CA GLU A37-74.38129.739-13.6501.0024.85C

Atom 327 CB GLU A37-73.67828.566-14.3131.0024.74C

Atom 330 CG GLU A37-72.18228.667-14.2851.0023.93C

Atom 333 CD GLU A37-71.51927.490-14.9371.0022.32C

Atom 334 OE1 GLU A37-72.20326.738-15.6571.0020.57O

Atom 335 OE2 GLU A37-70.30327.322-14.7281.0022.27O

Atoms 336C GLU A37-74.39130.927-14.6001.0024.69C

Atom 337O GLU A37-73.66631.891-14.3891.0024.49O

Atom 339N ALA A38-75.20330.850-15.6501.0024.68N

Atom 340 CA ALA A38-75.35231.960-16.5991.0024.87C

Atom 342 CB ALA A38-76.45331.656-17.6091.0024.53C

Atom 346C ALA A38-75.64333.278-15.8801.0025.08C

Atom 347O ALA A38-75.00934.295-16.1351.0025.21O

Atom 349N GLU A39-76.59133.228-14.9561.0025.35N

Atom 350 CA GLU A39-77.05034.400-14.2191.0025.51C

Atom 352 CB GLU A39-78.28334.014-13.3961.0025.95C

Atom 355 CG GLU A39-79.30235.119-13.1361.0027.03C

Atom 358 CD GLU A39-80.71534.557-12.9061.0028.70C

Atom 359 OE1 GLU A39-81.00633.416-13.3461.0027.40O

Atom 360 OE2 GLU A39-81.54035.266-12.2891.0031.12O

Atom 361C GLU A39-75.97034.966-13.3061.0025.11C

Atom 362O GLU A39-75.87036.167-13.1641.0025.28O

Atom 364N VAL A40-75.18234.107-12.6721.0024.86N

Atom 365 CA VAL A40-74.07934.568-11.8241.0024.69C

Atom 367 CB VAL A40-73.51133.420-10.9521.0024.56C

Atom 369 CG1 VAL A40-72.23933.857-10.2401.0023.69C

Atom 373 CG2 VAL A40-74.55332.955-9.9551.0024.68C

Atoms 377C VAL A40-72.97135.148-12.6981.0024.76C

Atom 378O VAL A40-72.33736.139-12.3621.0024.16O

Atom 380N ARG A41-72.74434.506-13.8311.0025.25N

Atom 381 CA ARG A41-71.72734.948-14.7691.0025.66C

Atom 383 CB ARG A41-71.57633.927-15.8961.0025.88C

Atom 386 CG ARG A41-70.72634.385-17.0621.0027.04C

Atom 389 CD ARG A41-71.51935.178-18.0951.0027.90C

Atom 392 NE ARG A41-70.65335.635-19.1801.0029.20N

Atom 394 CZ ARG A41-70.94636.615-20.0341.0029.94C

Atom 395 NH1 ARG A41-70.07736.945-20.9801.0029.86N

Atom 398 NH2 ARG A41-72.09637.273-19.9571.0030.54N

Atom 401C ARG A41-72.10436.301-15.3351.0025.60C

Atom 402O ARG A41-71.23737.113-15.6121.0025.77O

Atom 404N ARG A42-73.40036.521-15.5371.0025.50N

Atom 405 CA ARG A42-73.90037.810-15.9791.0025.39C

Atom 407 CB ARG A42-75.38937.723-16.3131.0025.09C

Atom 410 CG ARG A42-76.07739.062-16.4451.0023.84C

Atom 413 CD ARG A42-77.45938.906-16.9801.0022.37C

Atom 416 NE ARG A42-78.44838.554-15.9651.0021.69N

Atom 418 CZ ARG A42-79.70538.206-16.2481.0022.99C

Atom 419 NH1 ARG A42-80.12238.146-17.5171.0024.16N

Atom 422 NH2 ARG A42-80.55737.900-15.2751.0022.94N

Atom 425C ARG A42-73.66638.889-14.9251.0026.00C

Atom 426O ARG A42-73.17339.959-15.2441.0026.17O

Atom 428N GLU A43-74.01438.621-13.6731.0026.66N

Atom 429 CA GLU A43-73.93039.662-12.6501.0027.47C

Atom 431 CB GLU A43-74.74939.304-11.4011.0027.97C

Atom 434 CG GLU A43-76.27439.266-11.6611.0031.05C

Atom 437 CD GLU A43-76.86940.636-12.0631.0034.68C

Atom 438 OE1 GLU A43-76.80441.571-11.2221.0037.63O

Atom 439 OE2 GLU A43-77.39840.773-13.2051.0034.52O

Atom 440C GLU A43-72.49440.035-12.2751.0027.15C

Atom 441O GLU A43-72.29241.118-11.7161.0027.49O

Atom 443N ILE A44-71.51739.166-12.5881.0026.57N

Atom 444 CA ILE A44-70.09039.456-12.3341.0025.80C

Atom 446 CB ILE A44-69.20638.187-12.1871.0025.52C

Atom 448 CG1 ILE A44-69.62437.320-11.0101.0024.69C

Atom 451 CD1 ILE A44-68.82836.061-10.8991.0023.08C

Atom 455 CG2 ILE A44-67.79038.581-11.9161.0025.73C

Atom 459C ILE A44-69.52240.286-13.4721.0025.40C

Atom 460O ILE A44-68.74541.211-13.2361.0025.26O

Atom 462N ASN A45-69.91239.945-14.7001.0025.14N

Atoms 463 CA ASN A45-69.48040.669-15.9061.0025.02C

Atom 465 CB ASN A45-69.69639.813-17.1511.0024.69C

Atom 468 CG ASN A45-68.66238.735-17.3021.0024.01C

Atom 469 OD1 ASN A45-67.47039.013-17.3951.0023.81O

Atom 470 ND2 ASN A45-69.11137.490-17.3441.0023.28N

Atom 473C ASN A45-70.17742.014-16.1141.0025.52C

Atom 474O ASN A45-69.70442.836-16.8901.0025.40O

Atom 476N ASN A46-71.30842.210-15.4371.0026.33N

Atom 477 CA ASN A46-72.08543.453-15.4681.0026.72C

Atom 479 CB ASN A46-73.10243.404-14.3221.0026.31C

Atom 482 CG ASN A46-73.93544.641-14.2091.0024.24C

Atom 483 OD1 ASN A46-73.94845.472-15.0911.0022.38O

Atom 484 ND2 ASN A46-74.64544.766-13.1061.0021.64N

Atoms 487C ASN A46-71.18544.680-15.3491.0028.11C

Atom 488O ASN A46-70.60344.933-14.3041.0028.16O

Atom 490N GLU A47-71.08445.441-16.4331.0029.93N

Atom 491 CA GLU A47-70.12846.558-16.5441.0031.30C

Atom 493 CB GLU A47-69.93346.969-18.0131.0031.28C

Atom 496 CG GLU A47-69.73745.795-19.0201.0032.37C

Atom 499 CD GLU A47-71.06045.127-19.5451.0032.69C

Atom 500 OE1 GLU A47-72.05545.833-19.8161.0032.16O

Atom 501 OE2 GLU A47-71.08743.880-19.6991.0032.41O

Atom 502C GLU A47-70.58247.774-15.7291.0032.47C

Atom 503O GLU A47-69.76048.525-15.2301.0032.86O

Atom 505N LYS A48-71.89847.945-15.5851.0033.93N

Atom 506 CA LYS A48-72.49149.075-14.8611.0034.85C

Atom 508 CB LYS A48-73.66049.672-15.6841.0035.08C

Atom 511 CG LYS A48-73.22150.119-17.1261.0036.58C

Atom 514 CD LYS A48-74.03551.277-17.7511.0037.93C

Atom 517 CE LYS A48-75.35350.799-18.4151.0039.02C

Atoms 520 NZ LYS A48-75.15949.990-19.6691.0039.11N

Atom 524C LYS A48-72.92648.632-13.4651.0035.26C

Atom 525O LYS A48-74.01148.954-13.0151.0035.04O

Atom 527N ALA A49-72.05147.890-12.7901.0036.29N

Atom 528 CA ALA A49-72.32147.348-11.4561.0037.18C

Atom 530 CB ALA A49-71.82845.923-11.3531.0037.20C

Atom 534C ALA A49-71.61848.191-10.4181.0037.88C

Atom 535O ALA A49-70.48048.610-10.6381.0038.17O

Atom 537N GLU A50-72.27848.404-9.2801.0038.53N

Atom 538 CA GLU A50-71.73049.242-8.2131.0039.08C

Atom 540 CB GLU A50-72.79049.545-7.1461.0039.43C

Atom 543 CG GLU A50-72.70850.953-6.6001.0040.86C

Atom 546 CD GLU A50-73.08952.010-7.6391.0042.77C

Atom 547 OE1 GLU A50-74.22552.530-7.5701.0045.07O

Atom 548 OE2 GLU A50-72.26552.320-8.5301.0043.35O

Atom 549C GLU A50-70.56048.521-7.6001.0038.89C

Atom 550O GLU A50-70.69947.378-7.2011.0039.05O

Atom 552N PHE A51-69.41149.181-7.5361.0038.99N

Atom 553 CA PHE A51-68.16148.502-7.1961.0039.52C

Atom 555 CB PHE A51-67.00049.494-7.0981.0040.05C

Atom 558 CG PHE A51-66.46049.948-8.4311.0042.80C

Atom 559 CD1 PHE A51-66.13549.014-9.4351.0045.21C

Atom 561 CE1 PHE A51-65.61249.425-10.6751.0046.12C

Atom 563 CZ PHE A51-65.40350.790-10.9171.0047.21C

Atom 565 CE2 PHE A51-65.72651.741-9.9131.0046.72C

Atom 567 CD2 PHE A51-66.24751.310-8.6791.0045.05C

Atom 569C PHE A51-68.22347.687-5.9051.0039.05C

Atom 570O PHE A51-67.89746.506-5.9001.0039.28O

Atoms 572N LEU A52-68.64848.307-4.8131.0038.42N

Atom 573 CA LEU A52-68.70947.610-3.5281.0037.94C

Atom 575 CB LEU A52-69.08448.594-2.4131.0038.53C

Atom 578 CG LEU A52-68.05749.726-2.1811.0040.46C

Atom 580 CD1 LEU A52-68.69151.101-1.7871.0041.88C

Atom 584 CD2 LEU A52-67.02049.274-1.1411.0041.83C

Atom 588C LEU A52-69.66746.406-3.5321.0036.72C

Atom 589O LEU A52-69.51745.494-2.7241.0036.84O

Atom 591N THR A53-70.64946.398-4.4311.0035.37N

Atom 592 CA THR A53-71.54545.247-4.5691.0034.11C

Atom 594 CB THR A53-72.86745.594-5.2771.0033.87C

Atom 596 OG1 THR A53-73.33946.863-4.8281.0033.49O

Atom 598 CG2 THR A53-73.91744.535-4.9831.0033.70C

Atom 602C THR A53-70.85344.148-5.3591.0033.04C

Atom 603O THR A53-70.89342.977-4.9731.0032.90O

Atom 605N LEU A54-70.22844.528-6.4671.0031.76N

Atom 606 CA LEU A54-69.46943.578-7.2861.0031.13C

Atom 608 CB LEU A54-68.72144.308-8.3921.0030.92C

Atom 611 CG LEU A54-68.02843.437-9.4241.0030.27C

Atom 613 CD1 LEU A54-69.03442.769-10.3101.0029.56C

Atom 617 CD2 LEU A54-67.10844.306-10.2421.0031.15C

Atom 621C LEU A54-68.46642.808-6.4431.0030.60C

Atom 622O LEU A54-68.37841.587-6.5431.0030.30O

Atom 624N LEU A55-67.72543.551-5.6181.0030.09N

Atom 625 CA LEU A55-66.73043.000-4.6951.0029.47C

Atoms 627 CB LEU A55-66.00644.126-3.9441.0029.44C

Atoms 630 CG LEU A55-65.06945.017-4.7811.0029.74C

Atom 632 CD1 LEU A55-64.60946.255-4.0031.0029.43C

Atom 636 CD2 LEU A55-63.85944.234-5.2861.0029.64C

Atom 640C LEU A55-67.34042.024-3.6961.0028.87C

Atom 641O LEU A55-66.74640.991-3.3831.0028.98O

Atoms 643N GLU A56-68.52542.330-3.1981.0028.01N

Atom 644 CA GLU A56-69.16041.419-2.2561.0027.64C

Atoms 646 CB GLU A56-70.17242.173-1.3951.0028.19C

Atom 649 CG GLU A56-69.49743.167-. 4591.0029.75C

Atom 652 CD GLU A56-70.45743.858.4781.0033.04C

Atom 653 OE1 GLU A56-71.66743.538.4811.0034.46O

Atom 654 OE2 GLU A56-69.98844.7371.2261.0036.78O

Atoms 655C GLU A56-69.77640.200-2.9451.0026.37C

Atom 656O GLU A56-69.91439.146-2.3331.0026.02O

Atoms 658N LEU A57-70.13440.347-4.2181.0025.30N

Atom 659 CA LEU A57-70.56939.212-5.0361.0024.17C

Atoms 661 CB LEU A57-71.12539.680-6.3821.0023.71C

Atom 664 CG LEU A57-71.41738.568-7.3901.0022.27C

Atom 666 CD1 LEU A57-72.51537.675-6.8581.0019.31C

Atom 670 CD2 LEU A57-71.75239.167-8.7681.0020.30C

The atoms 674C LEU A57-69.40438.267-5.2841.0023.69C

Atom 675O LEU A57-69.54737.051-5.1361.0023.83O

Atom 677N ILE A58-68.26138.822-5.6821.0022.82N

Atom 678 CA ILE A58-67.07038.019-5.9251.0022.39C

Atom 680 CB ILE A58-65.88438.899-6.3551.0022.21C

Atom 682 CG1 ILE A58-66.08839.386-7.7921.0021.83C

Atom 685 CD1 ILE A58-65.00240.314-8.3201.0020.43C

Atom 689 CG2 ILE A58-64.56538.131-6.2451.0022.64C

Atom 693C ILE A58-66.71937.227-4.6621.0022.35C

Atom 694O ILE A58-66.52036.002-4.7061.0021.95O

Atom 696N ASP A59-66.67637.951-3.5431.0022.32N

Atom 697 CA ASP A59-66.39637.396-2.2151.0022.26C

Atom 699 CB ASP A59-66.57038.500-1.1711.0022.67C

Atom 702 CG ASP A59-66.12638.092.2131.0023.91C

Atom 703 OD1 ASP A59-65.27137.182.3381.0023.77O

Atom 704 OD2 ASP A59-66.64138.7181.1781.0027.12O

Atom 705C ASP A59-67.30436.216-1.9011.0021.79C

Atom 706O ASP A59-66.82835.102-1.6681.0021.71O

Atoms 708N ASN A60-68.61036.466-1.9261.0021.51N

Atom 709 CA ASN A60-69.61935.418-1.7591.0021.28C

Atom 711 CB ASN A60-71.01236.006-1.9581.0021.25C

Atom 714 CG ASN A60-71.47636.827-. 7761.0021.82C

Atom 715 OD1 ASN A60-71.06736.598.3641.0020.81O

Atom 716 ND2 ASN A60-72.36137.783-1.0431.0023.63N

Atoms 719C ASN A60-69.44534.240-2.7251.0021.22C

Atom 720O ASN A60-69.44433.053-2.3031.0020.95O

Atom 722N VAL A61-69.30834.566-4.0181.0020.83N

Atom 723 CA VAL A61-69.14733.536-5.0431.0020.57C

Atom 725 CB VAL A61-68.91534.122-6.4661.0020.53C

Atom 727 CG1 VAL A61-68.38233.042-7.4301.0019.44C

Atom 731 CG2 VAL A61-70.19034.758-7.0061.0019.75C

Atom 735C VAL A61-67.98132.646-4.6441.0020.62C

Atom 736O VAL A61-68.08031.431-4.6991.0020.56O

Atom 738N GLN A62-66.88833.255-4.2091.0020.76N

Atom 739 CA GLN A62-65.70332.481-3.8981.0021.18C

Atom 741 CB GLN A62-64.46133.379-3.8241.0021.39C

Atom 744 CG GLN A62-64.00733.920-5.1651.0021.64C

Atom 747 CD GLN A62-62.60834.512-5.1351.0022.04C

Atomic 748 OE1 GLN A62-61.89034.483-6.1451.0023.18O

Atom 749 NE2 GLN A62-62.21735.062-3.9891.0020.39N

Atom 752C GLN A62-65.89131.681-2.6071.0021.09C

Atom 753O GLN A62-65.54430.485-2.5541.0021.30O

Atom 755N ARG A63-66.44832.325-1.5831.0020.63N

Atom 756 CA ARG A63-66.59031.677-. 2731.0020.54C

Atom 758 CB ARG A63-67.02532.686.7861.0020.57C

Atom 761 CG ARG A63-66.03133.823.9301.0022.55C

Atom 764 CD ARG A63-66.21434.6322.1791.0024.93C

Atom 767 NE ARG A63-66.12333.7813.3551.0027.75N

Atom 769 CZ ARG A63-66.49634.1514.5731.0030.24C

Atom 770 NH1 ARG A63-66.97135.3854.7821.0031.79N

Atom 773 NH2 ARG A63-66.39933.2855.5811.0030.07N

Atom 776C ARG A63-67.55730.499-. 3381.0019.81C

Atom 777O ARG A63-67.28329.431.2091.0019.67O

Atom 779N LEU A64-68.66130.684-1.0571.0019.04N

Atom 780 CA LEU A64-69.63629.617-1.2461.0018.44C

Atom 782 CB LEU A64-70.86530.167-1.9541.0018.59C

Atom 785 CG LEU A64-71.66231.170-1.1401.0018.32C

Atom 787 CD1 LEU A64-72.66931.852-2.0341.0018.10C

Atom 791 CD2 LEU A64-72.33430.444.0041.0018.29C

Atoms 795C LEU A64-69.08928.436-2.0371.0017.80C

Atom 796O LEU A64-69.80227.453-2.2521.0017.79O

Atom 798N GLY A65-67.85028.573-2.5151.0017.07N

Atom 799 CA GLY A65-67.08427.480-3.0811.0016.27C

Atoms 802C GLY A65-67.13727.406-4.5881.0015.77C

Atom 803O GLY A65-66.89326.347-5.1541.0015.78O

Atoms 805N LEU A66-67.43928.521-5.2461.0015.24N

Atom 806 CA LEU A66-67.62128.537-6.7011.0014.93C

Atom 808 CB LEU A66-68.97729.146-7.0211.0014.84C

Atom 811 CG LEU A66-70.20428.334-6.6191.0013.97C

Atom 813 CD1 LEU A66-71.39129.260-6.6501.0013.74C

Atom 817 CD2 LEU A66-70.41527.125-7.5341.0011.22C

Atoms 821C LEU A66-66.53329.314-7.4541.0015.09C

Atom 822O LEU A66-66.62129.497-8.6781.0014.81O

Atom 824N GLY A67-65.51029.758-6.7201.0015.21N

Atom 825 CA GLY A67-64.40430.526-7.2801.0014.98C

Atom 828C GLY A67-63.87329.952-8.5691.0014.60C

Atom 829O GLY A67-63.89130.619-9.5791.0014.63O

Atom 831N TYR A68-63.41928.706-8.5231.0014.57N

Atom 832 CA TYR A68-62.83128.029-9.6881.0014.72C

Atom 834 CB TYR A68-62.60826.539-9.3721.0014.73C

Atom 837 CG TYR A68-63.85825.689-9.3301.0012.47C

Atom 838 CD1 TYR A68-64.16324.826-10.3661.0010.68C

Atom 840 CE1 TYR A68-65.31024.043-10.3401.0010.55C

Atom 842 CZ TYR A68-66.16324.119-9.2581.0010.41C

Atom 843 OH TYR A68-67.31123.349-9.2121.006.97O

Atom 845 CE2 TYR A68-65.86424.979-8.2101.0011.44C

Atom 847 CD2 TYR A68-64.72225.750-8.2521.0011.29C

Atom 849C TYR A68-63.64828.141-10.9801.0015.31C

Atom 850O TYR A68-63.10628.230-12.0831.0015.01O

Atom 852N ARG A69-64.95928.136-10.8161.0016.03N

Atom 853 CA ARG A69-65.88428.083-11.9221.0016.67C

Atom 855 CB ARG A69-67.22427.649-11.3481.0016.58C

Atom 858 CG ARG A69-68.33227.445-12.3351.0016.07C

Atom 861 CD ARG A69-69.37826.578-11.7011.0014.26C

Atom 864 NE ARG A69-68.91525.205-11.6771.0012.82N

Atom 866 CZ ARG A69-69.06324.346-12.6761.0012.42C

Atom 867 NH1 ARG A69-69.67624.694-13.7921.0012.27N

Atom 870 NH2 ARG A69-68.60123.119-12.5531.0013.23N

Atom 873C ARG A69-66.01029.409-12.6921.0017.62C

Atom 874O ARG A69-66.28129.401-13.8921.0017.10O

Atom 876N PHE A70-65.81130.529-11.9851.0019.11N

Atom 877 CA PHE A70-65.93631.891-12.5301.0019.96C

Atom 879 CB PHE A70-67.02432.666-11.7631.0019.89C

Atom 882 CG PHE A70-68.36532.010-11.7841.0018.68C

Atom 883 CD1 PHE A70-69.15832.082-12.9031.0018.05C

Atom 885 CE1 PHE A70-70.37631.452-12.9381.0018.03C

Atom 887 CZ PHE A70-70.82530.754-11.8511.0017.26C

Atom 889 CE2 PHE A70-70.05130.672-10.7361.0017.60C

Atom 891 CD2 PHE A70-68.82231.300-10.7001.0017.86C

Atom 893C PHE A70-64.62732.661-12.4001.0021.34C

Atom 894O PHE A70-64.62933.862-12.1711.0021.25O

Atoms 896N GLU A71-63.50131.977-12.5411.0023.19N

Atom 897 CA GLU A71-62.21132.591-12.2141.0024.60C

Atom 899 CB GLU A71-61.12731.524-12.0731.0025.03C

Atom 902 CG GLU A71-59.71732.059-11.8611.0027.10C

Atom 905 CD GLU A71-58.71230.949-11.5491.0030.10C

Atom 906 OE1 GLU A71-59.08430.007-10.7961.0032.05O

Atom 907 OE2 GLU A71-57.55831.027-12.0511.0030.50O

Atom 908C GLU A71-61.80933.644-13.2411.0025.23C

Atom 909O GLU A71-61.36234.717-12.8621.0025.54O

Atom 911N SER A72-61.97933.345-14.5301.0025.91N

Atom 912 CA SER A72-61.64134.294-15.5881.0026.37C

Atom 914 CB SER A72-61.65633.606-16.9411.0026.32C

Atom 917 OG SER A72-62.98533.278-17.2911.0027.28O

Atom 919C SER A72-62.60935.476-15.6081.0026.84C

Atom 920O SER A72-62.19736.601-15.8521.0027.02O

Atom 922N ASP A73-63.89335.214-15.3611.0027.45N

Atom 923 CA ASP A73-64.89536.277-15.2461.0027.87C

Atom 925 CB ASP A73-66.28935.705-14.9681.0027.99C

Atom 928 CG ASP A73-66.84234.913-16.1401.0029.49C

Atom 929 OD1 ASP A73-67.21535.530-17.1551.0030.90O

Atom 930 OD2 ASP A73-66.91633.667-16.0541.0031.85O

Atom 931C ASP A73-64.51837.221-14.1211.0027.86C

Atom 932O ASP A73-64.59838.435-14.2861.0028.05O

Atom 934N ILE A74-64.11836.652-12.9851.0027.88N

Atom 935 CA ILE A74-63.69837.422-11.8211.0027.98C

Atom 937 CB ILE A74-63.34836.521-10.6371.0027.71C

Atom 939 CG1 ILE A74-64.60736.007-9.9601.0027.60C

Atom 942 CD1 ILE A74-64.35534.846-9.0231.0027.67C

Atom 946 CG2 ILE A74-62.55137.272-9.6211.0026.82C

Atom 950C ILE A74-62.47238.252-12.1331.0028.80C

Atom 951O ILE A74-62.47539.453-11.9171.0029.00O

Atom 953N ARG A75-61.41537.616-12.6281.0029.80N

Atom 954 CA ARG A75-60.19738.341-12.9681.0030.79C

Atoms 956 CB ARG A75-59.28637.507-13.8411.0031.33C

Atom 959 CG ARG A75-58.50636.441-13.1151.0034.25C

Atom 962 CD ARG A75-57.28636.009-13.9291.0037.53C

Atom 965 NE ARG A75-56.23837.019-13.7991.0040.89N

Atom 967 CZ ARG A75-54.93436.807-13.9671.0044.24C

Atom 968 NH1 ARG A75-54.45935.602-14.2941.0045.02N

Atom 971 NH2 ARG A75-54.08937.821-13.7961.0045.88N

Atom 974C ARG A75-60.54839.596-13.7271.0030.95C

Atom 975O ARG A75-60.16340.685-13.3361.0031.27O

Atom 977N ARG A76-61.29339.435-14.8151.0031.31N

Atom 978 CA ARG A76-61.71240.567-15.6381.0031.62C

Atom 980 CB ARG A76-62.59340.106-16.7941.0031.97C

Atom 983 CG ARG A76-61.83339.392-17.8951.0032.91C

Atom 986 CD ARG A76-62.61539.453-19.2051.0034.43C

Atom 989 NE ARG A76-63.92538.803-19.1281.0035.66N

Atom 991 CZ ARG A76-64.11537.480-19.1061.0037.15C

Atom 992 NH1 ARG A76-63.08536.632-19.1291.0037.93N

Atom 995 NH2 ARG A76-65.34736.992-19.0481.0037.64N

Atom 998C ARG A76-62.45341.629-14.8491.0031.41C

Atom 999O ARG A76-62.14442.798-14.9661.0031.35O

Atom 1001N ALA A77-63.43741.230-14.0581.0031.53N

Atom 1002 CA ALA A77-64.13642.177-13.2111.0031.73C

Atom 1004 CB ALA A77-65.07441.468-12.2751.0031.69C

Atom 1008C ALA A77-63.10742.950-12.4231.0032.23C

Atom 1009O ALA A77-63.11644.176-12.4111.0032.42O

Atom 1011N LEU A78-62.19842.223-11.7861.0032.95N

Atom 1012 CA LEU A78-61.16842.838-10.9631.0033.51C

Atom 1014 CB LEU A78-60.31941.775-10.2651.0033.10C

Atom 1017 CG LEU A78-60.95941.077-9.0811.0032.30C

Atom 1019 CD1 LEU A78-59.96040.104-8.4721.0030.80C

Atom 1023 CD2 LEU A78-61.43842.117-8.0561.0031.89C

Atoms 1027C LEU A78-60.24943.752-11.7531.0034.70C

Atom 1028O LEU A78-59.79044.753-11.2141.0035.18O

Atom 1030N ASP A79-59.95543.404-13.0071.0035.91N

Atom 1031 CA ASP A79-59.05444.205-13.8281.0036.89C

Atom 1033 CB ASP A79-58.63743.452-15.0831.0037.06C

Atom 1036 CG ASP A79-57.51844.150-15.8211.0038.41C

Atom 1037 OD1 ASP A79-57.80045.080-16.6151.0039.85O

Atom 1038 OD2 ASP A79-56.34743.775-15.5921.0040.78O

Atoms 1039C ASP A79-59.72145.505-14.2201.0037.75C

Atom 1040O ASP A79-59.10546.568-14.1771.0037.82O

Atom 1042N ARG A80-60.98445.401-14.6151.0038.99N

Atom 1043 CA ARG A80-61.81446.558-14.9231.0039.88C

Atom 1045 CB ARG A80-63.19146.106-15.4271.0040.41C

Atom 1048 CG ARG A80-64.02547.183-16.1221.0042.77C

Atom 1051 CD ARG A80-65.34746.624-16.7181.0045.79C

Atom 1054 NE ARG A80-66.10745.799-15.7651.0048.55N

Atom 1056 CZ ARG A80-66.13644.457-15.7421.0050.37C

Atom 1057 NH1 ARG A80-65.45043.724-16.6361.0049.78N

Atom 1060 NH2 ARG A80-66.86843.835-14.8051.0050.77N

Atom 1063C ARG A80-61.94647.409-13.6681.0039.80C

Atom 1064O ARG A80-61.84048.630-13.7421.0040.37O

Atom 1066N PHE A81-62.13646.771-12.5161.0039.62N

Atom 1067 CA PHE A81-62.21647.505-11.2451.0039.61C

Atom 1069 CB PHE A81-62.39246.561-10.0531.0039.74C

Atom 1072 CG PHE A81-62.28247.247-8.7121.0038.81C

Atom 1073 CD1 PHE A81-63.23848.153-8.3151.0039.03C

Atom 1075 CE1 PHE A81-63.15348.787-7.1001.0039.69C

Atom 1077 CZ PHE A81-62.09548.515-6.2611.0039.54C

Atom 1079 CE2 PHE A81-61.13447.608-6.6471.0038.66C

Atom 1081 CD2 PHE A81-61.22846.986-7.8651.0038.27C

Atom 1083C PHE A81-61.00648.378-10.9701.0039.58C

Atom 1084O PHE A81-61.16549.535-10.5811.0039.76O

Atom 1086N VAL A82-59.81047.817-11.1421.0039.50N

Atom 1087 CA VAL A82-58.57548.562-10.8921.0039.47C

Atom 1089 CB VAL A82-57.31447.659-10.9771.0039.37C

Atom 1091 CG1 VAL A82-56.10848.426-11.5211.0039.06C

Atom 1095 CG2 VAL A82-57.00947.079-9.6141.0039.23C

Atom 1099C VAL A82-58.45749.755-11.8331.0039.54C

Atom 1100O VAL A82-58.22250.884-11.3781.0039.45O

Atom 1102N SER A83-58.67849.513-13.1261.0039.65N

Atom 1103 CA SER A83-58.46950.535-14.1571.0039.82C

Atom 1105 CB SER A83-58.19649.880-15.5261.0039.84C

Atom 1108 OG SER A83-59.13848.870-15.8291.0040.00O

Atom 1110C SER A83-59.61751.561-14.2191.0039.62C

Atom 1111O SER A83-60.14951.853-15.2861.0039.59O

Atom 1113N SER A84-59.95752.108-13.0521.0039.44N

Atom 1114 CA SER A84-60.92653.197-12.9101.0039.13C

Atom 1116 CB SER A84-62.23852.834-13.6181.0039.03C

Atom 1119 OG SER A84-62.62051.505-13.3251.0037.97O

Atom 1121C SER A84-61.24353.580-11.4461.0039.17C

Atom 1122O SER A84-62.18954.341-11.2301.0039.58O

Atom 1124N GLY A85-60.48253.077-10.4571.0038.74N

Atom 1125 CA GLY A85-60.79553.282-9.0241.0038.26C

Atom 1128C GLY A85-61.72452.238-8.4131.0037.79C

Atom 1129O GLY A85-61.52951.799-7.2731.0036.84O

Atom 1131N SER A94-63.55754.1871.9941.0028.27N

Atom 1132 CA SER A94-64.06952.8922.4761.0028.03C

Atom 1134 CB SER A94-64.85652.2251.3591.0027.84C

Atom 1137 OG SER A94-65.23450.9211.7431.0028.20O

Atom 1139C SER A94-62.99251.9102.9341.0027.83C

Atom 1140 OSER A94-62.33951.3252.0901.0028.15O

Atom 1142N LEU A95-62.81551.7054.2451.0027.70N

Atom 1143 CA LEU A95-61.81350.7284.7511.0027.59C

Atom 1145 CB LEU A95-61.69250.7476.2821.0027.49C

Atom 1148 CG LEU A95-60.87149.5966.9091.0027.47C

Atom 1150 CD1 LEU A95-59.40049.9006.9021.0027.70C

Atom 1154 CD2 LEU A95-61.29249.2748.3291.0027.50C

Atom 1158C LEU A95-62.17349.3144.3181.0027.71C

Atom 1159O LEU A95-61.30348.5373.9141.0027.73O

Atom 1161N HIS A96-63.46148.9894.4371.0027.74N

Atom 1162 CA HIS A96-64.00347.7153.9771.0027.54C

Atom 1164 CB HIS A96-65.49747.6804.2301.0027.57C

Atom 1167 CG HIS A96-66.16146.4823.6541.0028.65C

Atom 1168 ND1 HIS A96-65.79045.2013.9881.0030.59N

Atom 1170 CE1 HIS A96-66.54044.3413.3251.0031.88C

Atom 1172 NE2 HIS A96-67.38445.0212.5701.0032.06N

Atom 1174 CD2 HIS A96-67.16646.3642.7581.0030.47C

Atom 1176C HIS A96-63.70547.4502.4921.0027.09C

Atom 1177O HIS A96-63.12846.4252.1501.0027.18O

Atom 1179N GLY A97-64.07948.3861.6251.0026.55N

Atom 1180 CA GLY A97-63.76048.300.2051.0026.26C

Atom 1183C GLY A97-62.27748.112-. 0881.0026.23C

Atom 1184O GLY A97-61.91847.334-. 9741.0026.39O

Atom 1186N THR A98-61.41548.815.6531.0025.83N

Atom 1187 CA THR A98-59.96748.755.4351.0025.36C

Atom 1189 CB THR A98-59.20449.8471.2151.0025.07C

Atom 1191 OG1 THR A98-59.79651.123.9801.0023.62O

Atom 1193 CG2 THR A98-57.75549.905.7801.0024.88C

Atom 1197C THR A98-59.41647.389.8451.0025.69C

Atom 1198O THR A98-58.62246.802.1111.0025.66O

Atom 1200N ALA A99-59.84746.8902.0081.0025.95N

Atom 1201 CA ALA A99-59.46845.5402.4951.0025.93C

Atom 1203 CB ALA A99-59.94545.3303.9291.0025.82C

Atom 1207C ALA A99-59.98444.4041.5951.0025.64C

Atom 1208O ALA A99-59.20443.5991.1021.0025.38O

Atoms 1210N LEU A100-61.29044.3481.3711.0025.46N

Atom 1211 CA LEU A100-61.85643.335.4741.0025.55C

Atom 1213 CB LEU A100-63.36143.540.3261.0025.37C

Atom 1216 CG LEU A100-64.11842.464-. 4431.0025.41C

Atom 1218 CD1 LEU A100-64.03841.115.2811.0026.01C

Atom 1222 CD2 LEU A100-65.55542.893-. 6391.0025.19C

Atoms 1226C LEU A100-61.19643.353-. 9191.0025.70C

Atoms 1227O LEU A100-60.81942.301-1.4691.0025.36O

Atom 1229N SER A101-61.06444.550-1.4891.0025.77N

Atom 1230 CA SER A101-60.43444.688-2.8051.0025.67C

Atom 1232 CB SER A101-60.62946.098-3.3751.0025.83C

Atom 1235 OG SER A101-59.84047.064-2.6881.0026.98O

Atom 1237C SER A101-58.94744.336-2.7561.0025.01C

Atom 1238O SER A101-58.42743.705-3.6721.0024.94O

Atom 1240N PHE A102-58.27044.737-1.6871.0024.30N

Atom 1241 CA PHE A102-56.85244.436-1.5601.0023.99C

Atom 1243 CB PHE A102-56.29544.963-. 2291.0023.84C

Atom 1246 CG PHE A102-54.86044.606.0271.0023.24C

Atom 1247 CD1 PHE A102-53.84945.504-. 2591.0023.56C

Atom 1249 CE1 PHE A102-52.50745.182-. 0071.0024.50C

Atom 1251 CZ PHE A102-52.17543.941.5401.0024.27C

Atoms 1253 CE2 PHE A102-53.18043.042.8341.0023.95C

Atoms 1255 CD2 PHE A102-54.52043.376.5761.0023.45C

Atom 1257C PHE A102-56.67342.928-1.6791.0023.65C

Atom 1258O PHE A102-55.89042.442-2.5011.0023.55O

Atom 1260N ARG A103-57.44342.202-. 8801.0023.20N

Atom 1261 CA ARG A103-57.29840.765-. 7641.0022.84C

Atom 1263 CB ARG A103-58.25040.231.2911.0023.01C

Atom 1266 CG ARG A103-58.05438.774.5971.0023.93C

Atom 1269 CD ARG A103-58.70338.3761.9371.0023.84C

Atom 1272 NE ARG A103-60.15038.5381.9191.0022.36N

Atom 1274 CZ ARG A103-60.98237.7631.2401.0020.62C

Atom 1275 NH1 ARG A103-60.51236.773.4901.0020.19N

Atom 1278 NH2 ARG A103-62.28838.0031.2931.0020.32N

Atom 1281C ARG A103-57.60240.117-2.0821.0022.34C

Atom 1282O ARG A103-56.82639.303-2.5761.0022.37O

Atom 1284N LEU A104-58.72940.496-2.6671.0021.98N

Atom 1285 CA LEU A104-59.12939.926-3.9511.0021.60C

Atom 1287 CB LEU A104-60.50340.442-4.3781.0021.23C

Atom 1290 CG LEU A104-61.59039.832-3.5221.0020.30C

Atom 1292 CD1 LEU A104-62.94940.401-3.8561.0019.53C

Atom 1296 CD2 LEU A104-61.55438.344-3.7251.0019.71C

Atom 1300C LEU A104-58.10140.198-5.0401.0021.48C

Atom 1301O LEU A104-57.74339.294-5.7801.0021.62O

Atom 1303N LEU A105-57.62341.432-5.1391.0021.14N

Atom 1304 CA LEU A105-56.65541.747-6.1731.0021.05C

Atom 1306 CB LEU A105-56.35243.248-6.2051.0020.94C

Atom 1309 CG LEU A105-57.46544.165-6.7321.0020.06C

Atom 1311 CD1 LEU A105-57.06045.617-6.5801.0017.92C

Atom 1315 CD2 LEU A105-57.80443.857-8.1741.0019.18C

Atom 1319C LEU A105-55.37240.908-5.9971.0021.32C

Atoms 1320O LEU A105-54.84040.357-6.9761.0021.37O

Atom 1322N ARG A106-54.89340.777-4.7631.0021.25N

Atom 1323 CA ARG A106-53.67840.003-4.5281.0021.33C

Atom 1325 CB ARG A106-53.15140.211-3.1171.0021.53C

Atom 1328 CG ARG A106-51.77239.588-2.9171.0022.60C

Atom 1331 CD ARG A106-51.09840.091-1.6661.0023.60C

Atom 1334 NE ARG A106-50.37441.330-1.8971.0024.60N

Atom 1336 CZ ARG A106-49.60641.916-. 9891.0026.54C

Atom 1337 NH1 ARG A106-49.46941.380.2251.0026.98N

Atom 1340 NH2 ARG A106-48.96743.041-1.2951.0027.19N

Atom 1343C ARG A106-53.88838.517-4.7671.0021.19C

Atom 1344O ARG A106-52.99837.821-5.2781.0021.18O

Atom 1346N GLN A107-55.06138.028-4.3781.0021.09N

Atom 1347 CA GLN A107-55.42536.635-4.6181.0020.76C

Atom 1349 CB GLN A107-56.86136.378-4.1681.0020.51C

Atom 1352 CG GLN A107-57.32934.941-4.3271.0019.68C

Atom 1355 CD GLN A107-58.79034.772-4.0101.0018.26C

Atom 1356 OE1 GLN A107-59.39535.591-3.3341.0017.44O

Atom 1357 NE2 GLN A107-59.36633.698-4.4971.0018.48N

Atom 1360C GLN A107-55.30436.306-6.0941.0020.93C

Atom 1361O GLN A107-54.91735.212-6.4471.0021.45O

Atom 1363N HIS A108-55.64237.260-6.9511.0021.09N

Atom 1364 CA HIS A108-55.68637.030-8.3791.0021.28C

Atom 1366 CB HIS A108-57.02437.541-8.9131.0021.02C

Atom 1369 CG HIS A108-58.18236.706-8.4781.0019.70C

Atom 1370 ND1 HIS A108-58.63735.632-9.2101.0019.91N

Atom 1372 CE1 HIS A108-59.64135.060-8.5711.0019.27C

Atom 1374 NE2 HIS A108-59.85135.720-7.4491.0018.10N

Atom 1376 CD2 HIS A108-58.95036.753-7.3671.0018.98C

Atom 1378C HIS A108-54.45637.621-9.1081.0022.21C

Atom 1379O HIS A108-54.50537.980-10.3041.0021.80O

Atom 1381N GLY A109-53.34537.686-8.3751.0023.19N

Atom 1382 CA GLY A109-52.05538.007-8.9561.0024.17C

Atom 1385C GLY A109-51.81339.470-9.2751.0025.25C

Atom 1386O GLY A109-50.76739.802-9.8451.0025.26O

Atom 1388N PHE A110-52.75540.349-8.9171.0026.42N

Atom 1389 CA PHE A110-52.57541.783-9.1541.0027.33C

Atom 1391 CB PHE A110-53.89542.546-9.0671.0027.36C

Atomic 1394 CG PHE A110-54.83842.250-10.1931.0027.83C

Atom 1395 CD1 PHE A110-54.63342.801-11.4391.0028.69C

Atom 1397 CE1 PHE A110-55.49042.529-12.4881.0028.91C

Atom 1399 CZ PHE A110-56.56841.702-12.2951.0028.85C

Atom 1401 CE2 PHE A110-56.78741.146-11.0601.0028.67C

Atom 1403 CD2 PHE A110-55.92341.418-10.0131.0028.39C

Atom 1405C PHE A110-51.58242.369-8.1631.0028.25C

Atom 1406O PHE A110-51.44941.890-7.0241.0028.71O

Atom 1408N GLU A111-50.88643.411-8.6071.0029.05N

Atom 1409 CA GLU A111-49.95144.142-7.7601.0029.66C

Atom 1411 CB GLU A111-48.90244.803-8.6481.0030.37C

Atom 1414 CG GLU A111-47.75045.509-7.9471.0033.30C

Atom 1417 CD GLU A111-46.91646.342-8.9461.0038.00C

Atom 1418 OE1 GLU A111-46.31245.750-9.8851.0039.60O

Atom 1419 OE2 GLU A111-46.88647.594-8.8021.0040.87O

Atoms 1420C GLU A111-50.72445.184-6.9351.0028.98C

Atom 1421O GLU A111-51.29346.123-7.4951.0028.45O

Atom 1423N VAL A112-50.78744.961-5.6181.0028.47N

Atom 1424 CA VAL A112-51.28445.950-4.6551.0028.09C

Atom 1426 CB VAL A112-52.56445.501-3.9081.0027.76C

Atom 1428 CG1 VAL A112-53.74545.466-4.8361.0027.38C

Atom 1432 CG2 VAL A112-52.36044.167-3.2521.0027.80C

Atom 1436C VAL A112-50.19346.199-3.6311.0028.15C

Atom 1437O VAL A112-49.33945.354-3.4361.0027.90O

Atom 1439N SER A113-50.24147.354-2.9741.0028.54N

Atom 1440 CA SER A113-49.19447.782-2.0471.0028.93C

Atom 1442 CB SER A113-48.56349.064-2.5641.0029.12C

Atom 1445 OG SER A113-47.69249.644-1.6191.0029.57O

Atom 1447C SER A113-49.78048.041-. 6851.0029.13C

Atom 1448O SER A113-50.93748.426-. 5811.0028.90O

Atom 1450N GLN A114-48.98547.857.3671.0029.84N

Atom 1451 CA GLN A114-49.52448.0191.7361.0030.40C

Atom 1453 CB GLN A114-48.56847.5072.8301.0030.34C

Atom 1456 CG GLN A114-47.19948.1592.8441.0030.61C

Atom 1459 CD GLN A114-46.45647.9284.1471.0030.77C

Atom 1460 OE1 GLN A114-46.87647.1294.9821.0031.92O

Atom 1461 NE2 GLN A114-45.34148.6244.3241.0030.02N

Atom 1464C GLN A114-49.93949.4402.0681.0030.62C

Atom 1465O GLN A114-50.57349.6443.0941.0030.73O

Atom 1467N GLU A115-49.59250.4071.2161.0030.94N

Atom 1468 CA GLU A115-49.96351.7941.4581.0031.45C

Atom 1470 CB GLU A115-48.88152.777.9751.0031.86C

Atom 1473 CG GLU A115-48.48952.723-. 5091.0033.48C

Atom 1476 CD GLU A115-47.00653.100-. 7591.0036.13C

Atom 1477 OE1 GLU A115-46.10652.668.0221.0038.72O

Atom 1478 OE2 GLU A115-46.74153.811-1.7541.0035.70O

Atom 1479C GLU A115-51.33852.125.8951.0031.45C

Atom 1480O GLU A115-51.71653.283.8081.0031.80O

Atom 1482N ALA A116-52.10851.105.5491.0031.58N

Atom 1483 CA ALA A116-53.52451.286.2841.0031.67C

Atom 1485 CB ALA A116-54.07150.092-4611.0031.62C

Atom 1489C ALA A116-54.27351.4731.5961.0031.88C

Atom 1490O ALA A116-55.42851.8741.6041.0031.82O

Atom 1492N PHE A117-53.60851.1612.7021.0032.39N

Atom 1493 CA PHE A117-54.19351.2714.0301.0032.87C

Atom 1495 CB PHE A117-53.88450.0034.8561.0032.79C

Atom 1498 CG PHE A117-54.53948.7584.3231.0031.03C

Atom 1499 CD1 PHE A117-53.78247.7493.7601.0028.79C

Atom 1501 CE1 PHE A117-54.37946.6203.2651.0028.36C

Atom 1503 CZ PHE A117-55.75446.4893.3161.0029.50C

Atom 1505 CE2 PHE A117-56.52747.4933.8721.0029.91C

Atom 1507 CD2 PHE A117-55.91748.6134.3751.0030.09C

Atom 1509C PHE A117-53.68352.4934.7731.0033.71C

Atom 1510O PHE A117-54.01252.6785.9371.0033.61O

Atom 1512N SER A118-52.88653.3254.1071.0035.09N

Atom 1513 CA SER A118-52.18654.4294.7791.0036.12C

Atom 1515 CB SER A118-51.07354.9903.8951.0036.09C

Atom 1518 OG SER A118-51.60755.7472.8201.0035.96O

Atom 1520C SER A118-53.13455.5525.1841.0037.17C

Atom 1521O SER A118-52.87356.2556.1661.0037.22O

Atom 1523N GLY A119-54.23155.7054.4361.0038.40N

Atom 1524 CA GLY A119-55.22756.7354.7081.0039.47C

Atom 1527C GLY A119-56.25556.3985.7781.0040.62C

Atom 1528O GLY A119-57.25957.0865.8771.0040.74O

Atom 1530N PHE A120-56.02455.3446.5631.0042.13N

Atom 1531 CA PHE A120-56.90654.9717.6841.0043.27C

Atom 1533 CB PHE A120-57.51053.5867.4551.0043.21C

Atom 1536 CG PHE A120-58.17653.4396.1341.0042.36C

Atom 1537 CD1 PHE A120-59.41854.0065.9111.0041.23C

Atom 1539 CE1 PHE A120-60.03553.8804.6911.0040.87C

Atom 1541 CZ PHE A120-59.41453.1823.6751.0041.03C

Atom 1543 CE2 PHE A120-58.16752.6183.8831.0040.92C

Atom 1545 CD2 PHE A120-57.55652.7465.1061.0041.30C

Atom 1547C PHE A120-56.17954.9529.0191.0044.71C

Atom 1548O PHE A120-56.73254.48910.0251.0044.80O

Atom 1550N LYS A121-54.93955.4309.0211.0046.38N

Atom 1551 CA LYS A121-54.15355.51910.2351.0047.81C

Atom 1553 CB LYS A121-52.72255.0509.9571.0047.86C

Atom 1556 CG LYS A121-52.64853.5379.6481.0048.24C

Atom 1559 CD LYS A121-51.41753.1198.8231.0049.41C

Atom 1562 CE LYS A121-50.09553.1429.6211.0049.88C

Atom 1565 NZ LYS A121-49.94452.00510.5841.0049.89N

Atoms 1569C LYS A121-54.25756.96410.7351.0049.00C

Atom 1570O LYS A121-54.71257.83910.0001.0049.11O

Atom 1572N ASP A122-53.89957.20611.9951.0050.51N

Atom 1573 CA ASP A122-54.07858.53712.5961.0051.46C

Atom 1575 CB ASP A122-54.60458.44314.0501.0051.29C

Atom 1578 CG ASP A122-53.57057.91915.0361.0050.73C

Atom 1579 OD1 ASP A122-52.35358.02514.7771.0049.90O

Atom 1580 OD2 ASP A122-53.98857.39816.0881.0049.66O

Atom 1581C ASP A122-52.79259.35812.5021.0052.60C

Atom 1582O ASP A122-51.83058.95311.8351.0052.65O

Atom 1584N GLN A123-52.80260.51213.1721.0053.88N

Atom 1585 CA GLN A123-51.68061.45613.1951.0054.66C

Atom 1587 CB GLN A123-51.99362.59414.1781.0055.01C

Atom 1590 CG GLN A123-53.24963.44213.8311.0056.15C

Atom 1593 CD GLN A123-52.94364.73613.0641.0057.64C

Atom 1594 OE1 GLN A123-51.77965.10212.8591.0059.10O

Atom 1595 NE2 GLN A123-54.00165.43812.6521.0057.63N

Atom 1598C GLN A123-50.36560.77213.5911.0054.87C

Atom 1599O GLN A123-49.30961.07813.0341.0054.67O

Atom 1601N ASN A124-50.45859.83414.5381.0055.21N

Atom 1602 CA ASN A124-49.30059.13715.1091.0055.39C

Atom 1604 CB ASN A124-49.42159.12216.6371.0055.52C

Atom 1607 CG ASN A124-49.83360.47817.2021.0055.98C

Atom 1608 OD1 ASN A124-49.09361.46017.0911.0056.93O

Atom 1609 ND2 ASN A124-51.02660.54017.7971.0055.99N

Atom 1612C ASN A124-49.11657.70514.5891.0055.27C

Atom 1613O ASN A124-48.53056.86415.2711.0055.18O

Atom 1615N GLY A125-49.62657.43013.3911.0055.18N

Atom 1616 CA GLY A125-49.31156.19012.6721.0055.08C

Atom 1619C GLY A125-49.99454.89713.1191.0054.90C

Atom 1620O GLY A125-49.54353.80612.7501.0055.24O

Atom 1622N ASN A126-51.07255.00813.9001.0054.23N

Atom 1623 CA ASN A126-51.87153.85314.3291.0053.39C

Atom 1625 CB ASN A126-51.92753.78215.8521.0053.27C

Atom 1628 CG ASN A126-50.59653.42516.4661.0052.81C

Atom 1629 OD1 ASN A126-49.63653.11315.7641.0052.29O

Atom 1630 ND2 ASN A126-50.53253.46017.7891.0052.53N

Atom 1633C ASN A126-53.27453.97813.7711.0052.82C

Atom 1634O ASN A126-53.72455.08113.4941.0052.69O

Atom 1636N PHE A127-53.96852.85713.6071.0052.17N

Atom 1637 CA PHE A127-55.28752.87512.9621.0051.56C

Atom 1639 CB PHE A127-55.80551.45112.7211.0051.35C

Atom 1642 CG PHE A127-55.11950.73011.5871.0050.06C

Atom 1643 CD1 PHE A127-54.06849.85611.8311.0048.90C

Atom 1645 CE1 PHE A127-53.43749.18710.7891.0047.59C

Atom 1647 CZ PHE A127-53.85749.3839.4951.0047.40C

Atom 1649 CE2 PHE A127-54.90650.2449.2341.0047.96C

Atom 1651 CD2 PHE A127-55.53350.91510.2761.0048.85C

Atom 1653C PHE A127-56.30353.69013.7761.0051.35C

Atom 1654O PHE A127-56.34753.59415.0021.0051.09O

Atom 1656N LEU A128-57.10054.50013.0831.0051.15N

Atom 1657 CA LEU A128-58.14355.28013.7271.0051.09C

Atom 1659 CB LEU A128-59.03955.97912.6941.0051.17C

Atom 1662 CG LEU A128-58.46357.04611.7461.0051.31C

Atom 1664 CD1 LEU A128-59.57157.62810.8551.0050.76C

Atom 1668 CD2 LEU A128-57.76258.15712.5081.0050.98C

Atom 1672C LEU A128-58.99654.35314.5811.0051.06C

Atom 1673O LEU A128-59.57353.39314.0781.0050.94O

Atom 1675N GLU A129-59.05354.63715.8791.0051.12N

Atom 1676 CA GLU A129-59.91653.91316.8081.0050.99C

Atom 1678 CB GLU A129-60.01954.66518.1321.0051.14C

Atom 1681 CG GLU A129-58.85054.43119.0491.0052.04C

Atom 1684 CD GLU A129-58.90353.06919.6971.0053.22C

Atom 1685 OE1 GLU A129-58.04052.21919.3761.0054.19O

Atom 1686 OE2 GLU A129-59.82352.84820.5161.0053.51O

Atom 1687C GLU A129-61.31453.71216.2601.0050.66C

Atom 1688O GLU A129-61.79152.58716.2001.0050.83O

Atom 1690N ASN A130-61.96054.79915.8391.0050.28N

Atom 1691 CA ASN A130-63.38954.76515.4861.0050.03C

Atom 1693 CB ASN A130-63.91056.18215.1931.0050.09C

Atom 1696 CG ASN A130-63.28656.80513.9601.0050.37C

Atoms 1697 OD1 ASN A130-62.50456.17713.2491.0051.44O

Atom 1698 ND2 ASN A130-63.63458.05613.7011.0050.27N

Atom 1701C ASN A130-63.80453.78214.3691.0049.56C

Atom 1702O ASN A130-64.99353.58114.1311.0049.44O

Atom 1704N LEU A131-62.82853.17513.6991.0049.21N

Atom 1705 CA LEU A131-63.08752.10312.7291.0048.78C

Atom 1707 CB LEU A131-61.84651.83211.8751.0048.64C

Atom 1710 CG LEU A131-61.44552.93910.8981.0048.26C

Atom 1712 CD1 LEU A131-60.02952.70910.3751.0047.76C

Atom 1716 CD2 LEU A131-62.44153.0399.7541.0047.32C

Atom 1720C LEU A131-63.51650.79813.3941.0048.58C

Atom 1721O LEU A131-64.09349.93912.7311.0048.64O

Atom 1723N LYS A132-63.22550.64514.6891.0048.23N

Atom 1724 CA LYS A132-63.65049.47415.4651.0047.80C

Atom 1726 CB LYS A132-63.15649.58716.9131.0047.71C

Atom 1729 CG LYS A132-63.93050.61517.7281.0047.80C

Atom 1732 CD LYS A132-63.43050.77919.1531.0047.75C

Atom 1735 CE LYS A132-64.43851.57719.9821.0047.22C

Atom 1738 NZ LYS A132-63.76952.36421.0331.0046.65N

Atom 1742C LYS A132-65.18249.30815.4461.0047.56C

Atom 1743O LYS A132-65.69648.20415.6161.0047.76O

Atom 1745N GLU A133-65.90150.41315.2491.0047.18N

Atom 1746 CA GLU A133-67.37150.41215.1911.0046.79C

Atom 1748 CB GLU A133-67.89851.85015.3371.0046.95C

Atom 1751 CG GLU A133-67.84052.37616.7761.0047.56C

Atom 1754 CD GLU A133-67.61353.88616.8631.0048.41C

Atom 1755 OE1 GLU A133-68.24754.64816.0931.0047.67O

Atom 1756 OE2 GLU A133-66.79854.30417.7211.0048.92O

Atom 1757C GLU A133-67.94949.77013.9181.0046.10C

Atom 1758O GLU A133-69.14049.44613.8741.0046.11O

Atom 1760N ASP A134-67.10349.60112.8961.0045.11N

Atom 1761 CA ASP A134-67.47748.99511.6081.0044.06C

Atom 1763 CB ASP A134-66.93449.86810.4741.0043.97C

Atom 1766 CG ASP A134-67.38049.4119.1041.0044.08C

Atom 1767 OD1 ASP A134-68.07248.3738.9721.0043.42O

Atom 1768 OD2 ASP A134-67.02050.1168.1411.0044.84O

Atom 1769C ASP A134-66.91047.57011.5261.0043.12C

Atom 1770O ASP A134-65.78847.35711.0801.0043.19O

Atom 1772N ILE A135-67.70846.59411.9441.0041.85N

Atom 1773 CA ILE A135-67.21645.24712.2161.0040.75C

Atom 1775 CB ILE A135-68.18344.50713.1701.0040.80C

Atom 1777 CG1 ILE A135-68.22745.22614.5241.0041.21C

Atom 1780 CD1 ILE A135-69.35346.28314.6331.0042.86C

Atom 1784 CG2 ILE A135-67.77643.06313.3731.0040.88C

Atom 1788C ILE A135-66.98044.45710.9331.0039.67C

Atom 1789O ILE A135-66.16643.53710.9011.0039.37O

Atom 1791N LYS A136-67.69044.8289.8771.0038.62N

Atom 1792 CA LYS A136-67.46544.2568.5541.0037.88C

Atom 1794 CB LYS A136-68.52544.7497.5611.0038.33C

Atom 1797 CG LYS A136-69.95544.3427.8791.0040.17C

Atom 1800 CD LYS A136-70.48643.2626.9111.0042.97C

Atom 1803 CE LYS A136-71.62442.3897.5361.0044.00C

Atom 1806 NZ LYS A136-72.95043.0867.7261.0043.82N

Atom 1810C LYS A136-66.09744.6878.0471.0036.38C

Atom 1811O LYS A136-65.39943.9147.3881.0036.24O

Atom 1813N ALA A137-65.72845.9318.3411.0034.51N

Atom 1814 CA ALA A137-64.46346.4747.8761.0033.41C

Atom 1816 CB ALA A137-64.43247.9818.0581.0033.43C

Atom 1820C ALA A137-63.29145.8278.6001.0032.30C

Atom 1821O ALA A137-62.28845.4817.9951.0031.89O

Atom 1823N ILE A138-63.43745.6629.9051.0031.41N

Atom 1824 CA ILE A138-62.39545.07410.7371.0030.60C

Atom 1826 CB ILE A138-62.77045.13112.2381.0030.20C

Atom 1828 CG1 ILE A138-62.91446.57612.6891.0029.92C

Atom 1831 CD1 ILE A138-61.68147.41412.4171.0030.50C

Atom 1835 CG2 ILE A138-61.70644.47013.0851.0029.73C

Atom 1839C ILE A138-62.14043.63110.3201.0030.34C

Atom 1840O ILE A138-60.97243.20310.2121.0030.65O

Atom 1842N LEU A139-63.22742.88410.0981.0029.69N

Atom 1843 CA LEU A139-63.13441.5239.5621.0029.23C

Atom 1845 CB LEU A139-64.51740.9179.3321.0028.92C

Atom 1848 CG LEU A139-65.06640.18510.5451.0029.06C

Atom 1850 CD1 LEU A139-66.54139.87510.3521.0028.20C

Atom 1854 CD2 LEU A139-64.25038.92210.8131.0028.59C

Atom 1858C LEU A139-62.38241.5468.2471.0029.00C

Atom 1859O LEU A139-61.44440.7738.0351.0029.50O

Atom 1861N SER A140-62.79042.4587.3721.0028.14N

Atom 1862 CA SER A140-62.22242.5266.0541.0027.40C

Atom 1864 CB SER A140-62.91243.6195.2601.0027.35C

Atom 1867 OG SER A140-63.31043.1034.0151.0028.43O

Atom 1869C SER A140-60.72042.7776.1231.0026.77C

Atom 1870O SER A140-59.97542.2695.2981.0027.29O

Atom 1872N LEU A141-60.28543.5637.1051.0025.89N

Atom 1873 CA LEU A141-58.87243.8977.2831.0025.20C

Atom 1875 CB LEU A141-58.71745.1648.1551.0025.00C

Atom 1878 CG LEU A141-57.29845.6708.4891.0024.35C

Atom 1880 CD1 LEU A141-56.49745.9747.2321.0022.75C

Atom 1884 CD2 LEU A141-57.32946.8939.3851.0022.81C

Atom 1888C LEU A141-58.14042.7217.9201.0024.92C

Atom 1889O LEU A141-57.03442.3807.5211.0024.77O

Atom 1891N TYR A142-58.75142.1018.9211.0024.51N

Atom 1892 CA TYR A142-58.16340.9139.5141.0024.36C

Atom 1894 CB TYR A142-59.12040.32510.5381.0024.18C

Atom 1897 CG TYR A142-58.77438.94111.0461.0023.72C

Atom 1898 CD1 TYR A142-57.87838.76312.0911.0022.97C

Atom 1900 CE1 TYR A142-57.59337.50012.5821.0024.25C

Atom 1902 CZ TYR A142-58.22936.38612.0301.0025.75C

Atom 1903 OH TYR A142-57.96735.10012.5001.0026.97O

Atom 1905 CE2 TYR A142-59.12036.55110.9881.0025.02C

Atom 1907 CD2 TYR A142-59.39037.82010.5111.0024.01C

Atom 1909C TYR A142-57.87739.8968.4231.0024.39C

Atom 1910O TYR A142-56.82239.2768.3801.0024.19O

Atom 1912N GLU A143-58.84139.7607.5271.0024.59N

Atom 1913 CA GLU A143-58.82038.7286.5211.0024.70C

Atom 1915 CB GLU A143-60.19438.6365.8531.0024.69C

Atom 1918 CG GLU A143-60.65137.2195.5471.0027.21C

Atom 1921 CD GLU A143-61.12736.4266.7741.0030.20C

Atom 1922 OE1 GLU A143-60.26135.7767.3931.0033.40O

Atom 1923 OE2 GLU A143-62.35136.4217.0971.0030.50O

Atom 1924C GLU A143-57.70139.0105.5181.0024.08C

Atom 1925O GLU A143-56.98438.0905.1261.0024.53O

Atom 1927N ALA A144-57.53740.2815.1471.0023.30N

Atom 1928 CA ALA A144-56.51540.7154.1731.0022.79C

Atom 1930 CB ALA A144-56.78742.1543.7401.0022.49C

Atom 1934C ALA A144-55.07340.5984.7011.0022.42C

Atom 1935O ALA A144-54.12840.3803.9351.0022.36O

Atom 1937N SER A145-54.90940.7136.0121.0021.80N

Atom 1938 CA SER A145-53.59340.8226.6001.0021.36C

Atom 1940 CB SER A145-53.72641.1708.0661.0021.21C

Atom 1943 OG SER A145-54.33740.1008.7531.0021.59O

Atom 1945C SER A145-52.79739.5376.4761.0021.30C

Atom 1946O SER A145-51.57139.5336.7011.0021.50O

Atom 1948N PHE A146-53.48838.4396.1541.0021.00N

Atom 1949 CA PHE A146-52.82737.1276.0301.0020.41C

Atom 1951 CB PHE A146-53.79635.9796.3381.0020.20C

Atom 1954 CG PHE A146-54.13035.8737.7981.0019.91C

Atom 1955 CD1 PHE A146-53.38235.0878.6371.0020.48C

Atom 1957 CE1 PHE A146-53.67935.0129.9921.0020.59C

Atom 1959 CZ PHE A146-54.73135.74010.5081.0019.15C

Atoms 1961 CE2 PHE A146-55.46436.5369.6911.0019.10C

Atom 1963 CD2 PHE A146-55.15536.6158.3431.0020.16C

Atom 1965C PHE A146-52.17436.9644.6801.0019.76C

Atom 1966O PHE A146-51.30536.1164.5231.0019.46O

Atom 1968N LEU A147-52.55037.8193.7291.0019.34N

Atom 1969 CA LEU A147-51.93337.8042.4021.0019.13C

Atom 1971 CB LEU A147-52.90538.3671.3471.0018.67C

Atom 1974 CG LEU A147-53.96437.334.9191.0018.11C

Atom 1976 CD1 LEU A147-55.09037.2481.9611.0015.10C

Atom 1980 CD2 LEU A147-54.49437.609-. 4991.0016.50C

Atom 1984C LEU A147-50.58238.5252.3691.0019.10C

Atom 1985O LEU A147-49.99238.7151.3111.0019.44O

Atom 1987N ALA A148-50.07538.8823.5421.0019.13N

Atom 1988 CA ALA A148-48.96739.8063.6641.0018.84C

Atom 1990 CB ALA A148-48.76240.1675.1171.0018.78C

Atom 1994C ALA A148-47.72339.1843.1131.0018.85C

Atom 1995O ALA A148-47.54837.9753.2061.0018.80O

Atom 1997N LEU A149-46.86940.0132.5231.0019.08N

Atom 1998 CA LEU A149-45.50739.6012.2151.0019.32C

Atom 2000 CB LEU A149-45.05640.145.8631.0019.14C

Atom 2003 CG LEU A149-45.81939.650-. 3641.0019.16C

Atom 2005 CD1 LEU A149-45.03639.929-1.6451.0018.43C

Atom 2009 CD2 LEU A149-46.08938.175-. 2591.0020.09C

Atom 2013C LEU A149-44.52740.0293.3041.0019.60C

Atom 2014O LEU A149-44.79740.9164.1131.0019.20O

Atom 2016N GLU A150-43.38439.3613.3091.0020.42N

Atom 2017 CA GLU A150-42.28639.6744.2151.0021.03C

Atom 2019 CB GLU A150-41.09838.7413.9481.0021.03C

Atom 2022 CG GLU A150-40.49138.1765.2051.0022.23C

Atom 2025 CD GLU A150-39.43337.1174.9411.0024.34C

Atom 2026 OE1 GLU A150-39.18936.7863.7531.0024.53O

Atom 2027 OE2 GLU A150-38.84336.6255.9401.0025.82O

Atom 2028C GLU A150-41.88741.1304.0111.0021.29C

Atom 2029O GLU A150-41.61941.5442.8851.0021.13O

Atom 2031N GLY A151-41.89341.9035.0941.0021.89N

Atom 2032 CA GLY A151-41.63643.3415.0301.0022.25C

Atom 2035C GLY A151-42.87144.2215.1521.0022.67C

Atom 2036O GLY A151-42.75745.3975.4621.0022.84O

Atom 2038N GLU A152-44.05543.6694.9181.0023.19N

Atom 2039 CA GLU A152-45.26344.4744.9371.0023.76C

Atom 2041 CB GLU A152-46.35043.8134.1001.0023.79C

Atom 2044 CG GLU A152-46.03743.8902.6151.0023.98C

Atom 2047 CD GLU A152-47.14743.3681.7491.0023.72C

Atom 2048 OE1 GLU A152-47.22643.771.5741.0022.11O

Atom 2049 OE2 GLU A152-47.93942.5422.2411.0025.41O

Atom 2050C GLU A152-45.72244.7196.3651.0024.47C

Atom 2051O GLU A152-46.58644.0066.9061.0024.70O

Atom 2053N ASN A153-45.13445.7446.9691.0025.00N

Atom 2054 CA ASN A153-45.28745.9788.4041.0025.59C

Atom 2056 CB ASN A153-44.22146.9578.9021.0025.55C

Atom 2059 CG ASN A153-44.38648.3318.3081.0025.57C

Atom 2060 OD1 ASN A153-44.11448.5577.1281.0024.52O

Atom 2061 ND2 ASN A153-44.86749.2569.1171.0027.05N

Atom 2064C ASN A153-46.67946.4868.7721.0025.92C

Atom 2065O ASN A153-47.17246.2389.8721.0026.02O

Atom 2067N ILE A154-47.31047.1977.8471.0026.35N

Atom 2068 CA ILE A154-48.63847.7518.0821.0026.57C

Atom 2070 CB ILE A154-49.01348.7797.0071.0026.45C

Atom 2072 CG1 ILE A154-48.15950.0237.1641.0026.36C

Atom 2075 CD1 ILE A154-48.06050.7905.8831.0027.92C

Atom 2079 CG2 ILE A154-50.46749.1527.0891.0026.25C

Atom 2083C ILE A154-49.67446.6438.1111.0026.96C

Atom 2084O ILE A154-50.65046.7418.8511.0027.12O

Atom 2086N LEU A155-49.46745.5887.3201.0027.35N

Atom 2087 CA LEU A155-50.42244.4757.3041.0027.76C

Atom 2089 CB LEU A155-50.23843.5946.0671.0027.73C

Atom 2092 CG LEU A155-51.09043.9904.8751.0027.31C

Atom 2094 CD1 LEU A155-50.98045.4564.6831.0028.13C

Atom 2098 CD2 LEU A155-50.63343.2623.6231.0027.79C

Atom 2102C LEU A155-50.34043.6428.5821.0028.22C

Atom 2103O LEU A155-51.36143.2379.1121.0027.95O

Atom 2105N ASP A156-49.12843.3959.0681.0028.95N

Atom 2106 CA ASP A156-48.94442.72310.3481.0029.71C

Atom 2108 CB ASP A156-47.45042.46110.6391.0030.23C

Atom 2111 CG ASP A156-46.93841.12510.0271.0032.82C

Atom 2112 OD1 ASP A156-47.76540.2409.6581.0036.27O

Atom 2113 OD2 ASP A156-45.70040.9619.9231.0034.48O

Atom 2114C ASP A156-49.57043.53911.4691.0029.66C

Atom 2115O ASP A156-50.10942.96912.4251.0029.81O

Atom 2117N GLU A157-49.51444.86611.3451.0029.69N

Atom 2118 CA GLU A157-50.12945.76812.3291.0029.57C

Atom 2120 CB GLU A157-49.58147.18612.1781.0029.71C

Atom 2123 CG GLU A157-48.16447.32612.7121.0030.53C

Atom 2126 CD GLU A157-47.45548.54412.1691.0031.96C

Atom 2127 OE1 GLU A157-48.16749.49111.7411.0033.56O

Atom 2128 OE2 GLU A157-46.19548.54612.1661.0031.54O

Atom 2129C GLU A157-51.64945.77112.2301.0029.16C

Atom 2130O GLU A157-52.33045.81913.2411.0029.00O

Atom 2132N ALA A158-52.17245.71611.0101.0028.86N

Atom 2133 CA ALA A158-53.60645.57010.7921.0028.79C

Atom 2135 CB ALA A158-53.89345.4569.3011.0028.44C

Atom 2139C ALA A158-54.17144.35211.5361.0028.93C

Atom 2140O ALA A158-55.26544.40212.0981.0028.77O

Atom 2142N LYS A159-53.41643.26011.5281.0029.19N

Atom 2143 CA LYS A159-53.84942.02212.1431.0029.57C

Atom 2145 CB LYS A159-52.92940.88011.7101.0029.62C

Atom 2148 CG LYS A159-53.29739.51312.2581.0030.27C

Atom 2151 CD LYS A159-52.76538.36511.3871.0031.78C

Atom 2154 CE LYS A159-51.25938.13211.5251.0033.15C

Atom 2157 NZ LYS A159-50.91136.69611.2481.0033.88N

Atom 2161C LYS A159-53.86642.16013.6701.0029.99C

Atom 2162O LYS A159-54.76741.64214.3321.0030.29O

Atom 2164N VAL A160-52.88642.86214.2361.0030.07N

Atom 2165 CA VAL A160-52.84043.04715.6961.0030.03C

Atom 2167 CB VAL A160-51.52043.69116.1621.0029.88C

Atom 2169 CG1 VAL A160-51.51543.86317.6711.0028.94C

Atom 2173 CG2 VAL A160-50.34142.84815.7071.0030.23C

Atom 2177C VAL A160-53.99643.92516.1491.0030.05C

Atom 2178O VAL A160-54.54443.75217.2341.0030.31O

Atom 2180N PHE A161-54.35544.86215.2901.0030.08N

Atom 2181 CA PHE A161-55.40745.80815.5581.0030.09C

Atom 2183 CB PHE A161-55.25546.99314.5981.0029.92C

Atom 2186 CG PHE A161-56.37047.97414.6541.0028.52C

Atom 2187 CD1 PHE A161-56.34749.00515.5541.0027.92C

Atom 2189 CE1 PHE A161-57.36149.90315.6001.0028.06C

Atom 2191 CZ PHE A161-58.41149.78314.7331.0028.76C

Atom 2193 CE2 PHE A161-58.44148.75713.8261.0028.31C

Atom 2195 CD2 PHE A161-57.42947.86913.7891.0028.16C

Atom 2197C PHE A161-56.74645.12315.3881.0030.55C

Atom 2198O PHE A161-57.59845.20316.2581.0030.53O

Atom 2200N ALA A162-56.93044.43814.2711.0031.34N

Atom 2201 CA ALA A162-58.19343.77014.0231.0032.26C

Atom 2203 CB ALA A162-58.21743.13912.6431.0032.31C

Atom 2207C ALA A162-58.50042.73415.1181.0033.09C

Atom 2208O ALA A162-59.55742.81415.7351.0033.83O

Atom 2210N ILE A163-57.58741.79915.3931.0033.59N

Atom 2211 CA ILE A163-57.82640.79916.4381.0034.02C

Atom 2213 CB ILE A163-56.59739.90716.7451.0033.98C

Atom 2215 CG1 ILE A163-56.23539.00815.5661.0034.37C

Atom 2218 CD1 ILE A163-54.87838.31715.7221.0034.38C

Atom 2222 CG2 ILE A163-56.88338.99517.9191.0033.38C

Atom 2226C ILE A163-58.22541.47217.7441.0034.75C

Atom 2227O ILE A163-59.18941.06418.3731.0035.03O

Atom 2229N SER A164-57.50142.50418.1561.0035.76N

Atom 2230 CA SER A164-57.76343.11719.4631.0036.59C

Atom 2232 CB SER A164-56.82844.29319.7351.0036.59C

Atom 2235 OG SER A164-57.35045.48519.1641.0036.46O

Atom 2237C SER A164-59.19643.61119.5561.0037.42C

Atom 2238O SER A164-59.86043.42020.5711.0037.38O

Atom 2240N HIS A165-59.66144.25118.4861.0038.51N

Atom 2241 CA HIS A165-60.99044.85118.4671.0039.40C

Atom 2243 CB HIS A165-61.00846.09717.5741.0039.76C

Atom 2246 CG HIS A165-60.46747.32318.2511.0042.06C

Atom 2247 ND1 HIS A165-59.20547.82118.0001.0044.21N

Atom 2249 CE1 HIS A165-58.99848.89318.7481.0045.04C

Atom 2251 NE2 HIS A165-60.08049.10619.4781.0044.99N

Atom 2253 CD2 HIS A165-61.01148.13519.1921.0043.76C

Atom 2255C HIS A165-62.07843.87218.0601.0039.38C

Atom 2256O HIS A165-63.24844.24418.0671.0039.43O

Atom 2258N LEU A166-61.68342.63217.7451.0039.54N

Atom 2259 CA LEU A166-62.58941.55017.3261.0039.55C

Atom 2261 CB LEU A166-62.00140.76616.1541.0039.28C

Atom 2264 CG LEU A166-62.15641.33914.7521.0038.23C

Atom 2266 CD1 LEU A166-61.36140.50113.8051.0037.53C

Atom 2270 CD2 LEU A166-63.59441.36714.3321.0037.21C

Atom 2274C LEU A166-62.84240.55518.4381.0040.08C

Atom 2275O LEU A166-63.99140.22018.7331.0040.42O

Atom 2277N LYS A167-61.76640.07419.0521.0040.58N

Atom 2278 CA LYS A167-61.87539.09020.1331.0041.09C

Atom 2280 CB LYS A167-60.49138.63220.5951.0041.13C

Atom 2283 CG LYS A167-59.89739.39921.7681.0042.16C

Atom 2286 CD LYS A167-58.42139.03522.0131.0044.45C

Atom 2289 CE LYS A167-58.07037.56121.6541.0045.56C

Atom 2292 NZ LYS A167-56.61037.23721.7981.0046.20N

Atom 2296C LYS A167-62.67839.58421.3371.0041.23C

Atom 2297O LYS A167-62.99438.79322.2151.0041.47O

Atom 2299N GLU A168-62.99540.88421.3521.0041.49N

Atom 2300 CA GLU A168-63.70441.58322.4371.0041.42C

Atom 2302 CB GLU A168-65.20141.73022.1001.0041.27C

Atom 2305 CG GLU A168-65.99540.42422.0161.0041.01C

Atom 2308 CD GLU A168-66.92840.32820.7871.0040.84C

Atom 2309 OE1 GLU A168-66.70141.04019.7701.0039.82O

Atom 2310 OE2 GLU A168-67.88439.50920.8451.0039.04O

Atom 2311C GLU A168-63.48441.00423.8431.0041.66C

Atom 2312O GLU A168-62.43541.23124.4691.0041.46O

Atom 2314N GLU A172-71.66838.96121.1921.0055.65N

Atom 2315 CA GLU A172-73.05239.15320.7211.0056.00C

Atom 2317 CB GLU A172-73.87637.88020.9371.0056.27C

Atom 2320 CG GLU A172-73.19836.62020.3901.0057.12C

Atom 2323 CD GLU A172-74.05635.36320.5161.0058.18C

Atom 2324 OE1 GLU A172-75.30035.48020.6221.0058.84O

Atom 2325 OE2 GLU A172-73.48034.24920.4981.0058.98O

Atom 2326C GLU A172-73.76640.38621.3341.0055.70C

Atom 2327O GLU A172-74.95640.34721.6881.0054.95O

Atom 2329N LYS A173-72.98741.45821.4861.0055.58N

Atom 2330 CA LYS A173-73.49642.83121.4661.0055.43C

Atom 2332 CB LYS A173-72.64943.74122.3571.0055.51C

Atom 2335 CG LYS A173-72.52743.22323.7931.0056.07C

Atom 2338 CD LYS A173-72.80344.29124.8681.0055.87C

Atom 2341 CE LYS A173-73.11143.64226.2211.0055.20C

Atom 2344 NZ LYS A173-72.89344.57627.3481.0054.63N

Atom 2348C LYS A173-73.44943.29720.0091.0055.01C

Atom 2349O LYS A173-74.09144.27419.6251.0054.97O

Atom 2351N ILE A174-72.64742.58119.2231.0054.57N

Atom 2352 CA ILE A174-72.71342.55017.7671.0054.22C

Atom 2354 CB ILE A174-71.42941.84517.2271.0054.21C

Atom 2356 CG1 ILE A174-70.19642.72417.4741.0054.73C

Atom 2359 CD1 ILE A174-68.85841.94917.5531.0055.78C

Atom 2363 CG2 ILE A174-71.53241.50415.7591.0054.06C

Atom 2367C ILE A174-73.95741.74417.3841.0053.88C

Atom 2368O ILE A174-74.58741.13418.2501.0053.83O

Atom 2370N GLY A175-74.33241.74716.1071.0053.59N

Atom 2371 CA GLY A175-75.35140.81715.6131.0053.51C

Atom 2374C GLY A175-75.13039.39516.1261.0053.43C

Atom 2375O GLY A175-74.11939.10516.7601.0053.80O

Atom 2377N LYS A176-76.07038.49515.8611.0053.10N

Atom 2378 CA LYS A176-75.92637.09816.2861.0052.68C

Atom 2380 CB LYS A176-77.29136.52216.6771.0052.99C

Atom 2383 CG LYS A176-78.00337.38717.7461.0054.12C

Atom 2386 CD LYS A176-79.20136.69718.4361.0054.57C

Atom 2389 CE LYS A176-79.50337.36919.7921.0054.79C

Atom 2392 NZ LYS A176-80.45836.59820.6531.0055.20N

Atom 2396C LYS A176-75.24636.26715.1961.0051.83C

Atom 2397O LYS A176-74.39335.43315.4861.0051.69O

Atom 2399N GLU A177-75.60936.52013.9401.0050.90N

Atom 2400 CA GLU A177-74.97535.85412.8001.0050.19C

Atom 2402 CB GLU A177-75.79236.06211.5071.0050.41C

Atom 2405 CG GLU A177-75.50637.36810.7351.0051.03C

Atom 2408 CD GLU A177-76.40337.5729.5071.0052.17C

Atom 2409 OE1 GLU A177-75.95538.2768.5691.0052.63O

Atom 2410 OE2 GLU A177-77.54637.0489.4791.0052.03O

Atoms 2411C GLU A177-73.54936.36912.6071.0049.10C

Atom 2412O GLU A177-72.62635.59712.3211.0049.53O

Atoms 2414N LEU A178-73.38837.68112.7701.0047.39N

Atom 2415 CA LEU A178-72.11038.37112.5751.0045.63C

Atom 2417 CB LEU A178-72.35239.87712.6151.0045.59C

Atom 2420 CG LEU A178-71.28040.80912.0851.0045.45C

Atom 2422 CD1 LEU A178-70.96940.51510.6201.0045.45C

Atom 2426 CD2 LEU A178-71.76542.23312.2791.0044.63C

Atoms 2430C LEU A178-71.09537.97913.6341.0044.06C

Atom 2431O LEU A178-69.90238.01213.3871.0043.70O

Atom 2433N ALA A179-71.58637.61114.8101.0042.54N

Atom 2434 CA ALA A179-70.75337.04115.8471.0041.66C

Atom 2436 CB ALA A179-71.54536.88417.1221.0041.69C

Atom 2440C ALA A179-70.19335.69515.4161.0040.75C

Atom 2441O ALA A179-69.07835.35115.7691.0040.61O

Atom 2443N GLU A180-70.97434.93114.6641.0039.88N

Atom 2444 CA GLU A180-70.51833.63914.1431.0039.40C

Atom 2446 CB GLU A180-71.71032.78113.7181.0039.74C

Atom 2449 CG GLU A180-72.65032.41514.8651.0040.88C

Atom 2452 CD GLU A180-73.91331.71014.3981.0042.02C

Atom 2453 OE1 GLU A180-74.38032.02213.2711.0043.05O

Atom 2454 OE2 GLU A180-74.43730.85715.1661.0041.93O

Atom 2455C GLU A180-69.56533.80512.9601.0038.29C

Atom 2456O GLU A180-68.73932.94012.6991.0038.23O

Atom 2458N GLN A181-69.70434.91112.2401.0036.92N

Atom 2459 CA GLN A181-68.74835.29911.2231.0035.74C

Atom 2461 CB GLN A181-69.27236.51610.4631.0035.94C

Atom 2464 CG GLN A181-68.93136.5378.9751.0036.93C

Atom 2467 CD GLN A181-69.69335.4928.1761.0037.72C

Atom 2468 OE1 GLN A181-70.76935.0678.5671.0038.78O

Atom 2469 NE2 GLN A181-69.13935.0837.0501.0038.11N

Atom 2472C GLN A181-67.40635.63211.8811.0034.64C

Atom 2473O GLN A181-66.34835.41111.2941.0034.73O

Atom 2475N VAL A182-67.44836.15813.1021.0033.29N

Atom 2476 CA VAL A182-66.22436.48813.8421.0032.28C

Atom 2478 CB VAL A182-66.43337.65314.8551.0032.10C

Atom 2480 CG1 VAL A182-66.32838.99114.1661.0031.51C

Atom 2484 CG2 VAL A182-65.42037.59415.9571.0031.69C

Atom 2488C VAL A182-65.61335.29814.5751.0031.49C

Atom 2489O VAL A182-64.39635.23014.6681.0031.43O

Atom 2491N SER A183-66.42234.37815.1061.0030.56N

Atom 2492 CA SER A183-65.86033.17415.7441.0030.16C

Atom 2494 CB SER A183-66.92632.25316.3271.0030.29C

Atom 2497 OG SER A183-67.79632.93417.2141.0032.35O

Atom 2499C SER A183-65.11132.40314.6921.0029.30C

Atom 2500O SER A183-63.97431.98114.9031.0029.32O

Atom 2502N HIS A184-65.76832.25213.5461.0028.24N

Atom 2503 CA HIS A184-65.21531.57812.3791.0027.36C

Atom 2505 CB HIS A184-66.24531.65311.2541.0027.41C

Atom 2508 CG HIS A184-65.93030.80710.0641.0026.90C

Atom 2509 ND1 HIS A184-65.48429.51110.1661.0027.76N

Atoms 2511 CE1 HIS A184-65.32129.0098.9551.0027.47C

Atom 2513 NE2 HIS A184-65.66129.9298.0751.0026.52N

Atoms 2515 CD2 HIS A184-66.05931.0588.7421.0026.61C

Atom 2517C HIS A184-63.89832.20011.9401.0026.69C

Atom 2518O HIS A184-62.88131.52511.8621.0026.44O

Atom 2520N ALA A185-63.90933.49811.6751.0026.11N

Atom 2521 CA ALA A185-62.71134.17611.2051.0025.63C

Atom 2523 CB ALA A185-62.97035.62711.1091.0025.74C

Atom 2527C ALA A185-61.55233.91712.1531.0025.33C

Atom 2528O ALA A185-60.45133.57211.7251.0025.79O

Atom 2530N LEU A186-61.81434.06613.4501.0024.77N

Atom 2531 CA LEU A186-60.77633.94014.4701.0024.05C

Atom 2533 CB LEU A186-61.25634.49815.8141.0023.63C

Atom 2536 CG LEU A186-61.51636.01215.9031.0022.51C

Atom 2538 CD1 LEU A186-62.05736.39917.2661.0020.79C

Atom 2542 CD2 LEU A186-60.27336.79315.6131.0021.13C

Atom 2546C LEU A186-60.31632.49714.6131.0024.02C

Atom 2547O LEU A186-59.16932.25014.9431.0024.27O

Atom 2549N GLU A187-61.20131.54314.3471.0023.88N

Atom 2550 CA GLU A187-60.83630.11714.3481.0023.53C

Atom 2552 CB GLU A187-62.02929.27013.9191.0023.66C

Atom 2555 CG GLU A187-61.94527.82814.3161.0025.26C

Atom 2558 CD GLU A187-63.04926.97113.6931.0028.04C

Atom 2559 OE1 GLU A187-63.67227.39312.6811.0028.67O

Atom 2560 OE2 GLU A187-63.28825.85814.2251.0029.72O

Atom 2561C GLU A187-59.68629.83813.3951.0022.92C

Atom 2562O GLU A187-58.76529.09113.7291.0022.53O

Atom 2564N LEU A188-59.76330.44612.2091.0022.46N

Atom 2565 CA LEU A188-58.79930.24611.1211.0022.07C

Atom 2567 CB LEU A188-58.80228.79410.6351.0022.11C

Atom 2570 CG LEU A188-57.87628.3629.4931.0022.17C

Atom 2572 CD1 LEU A188-56.45628.0519.9611.0021.62C

Atom 2576 CD2 LEU A188-58.46427.1348.8221.0022.40C

Atom 2580C LEU A188-59.23731.1379.9851.0021.69C

Atom 2581O LEU A188-60.38031.0759.5631.0021.53O

Atom 2583N PRO A189-58.33331.9739.4741.0021.46N

Atom 2584 CA PRO A189-58.74532.9358.4721.0021.18C

Atom 2586 CB PRO A189-57.59233.9368.4861.0021.03C

Atom 2589 CG PRO A189-56.42333.1188.7571.0021.21C

Atom 2592 CD PRO A189-56.87331.9929.6681.0021.61C

Atom 2595C PRO A189-58.94632.3147.0761.0020.96C

Atom 2596O PRO A189-58.41831.2476.7931.0021.02O

Atom 2597N LEU A190-59.71432.9946.2261.0020.89N

Atom 2598 CA LEU A190-60.01832.5334.8671.0020.74C

Atom 2600 CB LEU A190-60.59733.6904.0531.0020.76C

Atom 2603 CG LEU A190-62.09033.9244.2591.0021.35C

Atoms 2605 CD1 LEU A190-62.53735.1963.5781.0020.54C

Atoms 2609 CD2 LEU A190-62.88932.7123.7201.0023.39C

Atom 2613C LEU A190-58.81431.9714.1121.0020.35C

Atom 2614O LEU A190-58.85930.8713.5461.0020.08O

Atom 2616N HIS A191-57.73432.7464.1321.0019.81N

Atom 2617 CA HIS A191-56.53732.4483.3641.0018.89C

Atom 2619 CB HIS A191-55.54833.5923.5361.0018.92C

Atom 2622 CG HIS A191-54.37233.5202.6231.0018.51C

Atom 2623 ND1 HIS A191-54.48233.6471.2581.0018.08N

Atom 2625 CE1 HIS A191-53.28133.544.7181.0018.96C

Atom 2627 NE2 HIS A191-52.39733.3711.6841.0017.01N

Atom 2629 CD2 HIS A191-53.05433.3552.8841.0017.94C

Atom 2631C HIS A191-55.88931.1423.7591.0018.32C

Atom 2632O HIS A191-55.21730.5312.9421.0017.98O

Atom 2634N ARG A192-56.09330.7195.0061.0018.06N

Atom 2635 CA ARG A192-55.50229.4805.5231.0017.99C

Atom 2637 CB ARG A192-54.94029.7226.9091.0017.77C

Atom 2640 CG ARG A192-53.82230.6836.8811.0018.47C

Atom 2643 CD ARG A192-53.08230.7488.1961.0019.80C

Atom 2646 NE ARG A192-52.17431.9008.2241.0020.33N

Atom 2648 CZ ARG A192-51.17632.0489.0771.0020.10C

Atom 2649 NH1 ARG A192-50.92831.1139.9721.0021.72N

Atom 2652 NH2 ARG A192-50.40733.1199.0191.0020.79N

Atom 2655C ARG A192-56.47728.3115.5901.0018.00C

Atom 2656O ARG A192-56.06727.1705.8711.0018.21O

Atom 2658N ARG A193-57.75828.5885.3351.0017.59N

Atom 2659 CA ARG A193-58.77927.5635.3821.0017.16C

Atom 2661 CB ARG A193-60.14128.1645.7411.0017.45C

Atom 2664 CG ARG A193-61.10927.1326.3221.0018.70C

Atom 2667 CD ARG A193-62.47927.6826.6861.0020.20C

Atom 2670 NE ARG A193-62.42328.6827.7511.0022.59N

Atom 2672 CZ ARG A193-62.38628.4359.0671.0024.12C

Atom 2673 NH1 ARG A193-62.39527.1989.5751.0022.66N

Atom 2676 NH2 ARG A193-62.34829.4699.8981.0026.36N

Atom 2679C ARG A193-58.87126.8424.0581.0016.63C

Atom 2680O ARG A193-58.86127.4613.0051.0015.93O

Atom 2682N THR A194-58.95525.5184.1491.0016.72N

Atom 2683 CA THR A194-59.33224.6383.0511.0016.88C

Atom 2685 CB THR A194-59.52023.2503.5921.0016.43C

Atom 2687 OG1 THR A194-58.25222.6053.5831.0017.74O

Atom 2689 CG2 THR A194-60.45422.4412.7541.0018.43C

Atom 2693C THR A194-60.60725.1122.3841.0017.28C

Atom 2694O THR A194-61.44125.7343.0221.0017.44O

Atom 2696N GLN A195-60.76524.8551.0911.0018.05N

Atom 2697 CA GLN A195-61.92525.402.3971.0018.76C

Atom 2699 CB GLN A195-61.76825.381-1.1141.0018.87C

Atom 2702 CG GLN A195-63.14525.523-1.7611.0020.75C

Atom 2705 CD GLN A195-63.09525.922-3.1791.0023.41C

Atom 2706 OE1 GLN A195-62.03126.088-3.7331.0027.07O

Atom 2707 NE2 GLN A195-64.24826.090-3.7911.0025.02N

Atom 2710C GLN A195-63.24324.704.7651.0018.93C

Atom 2711O GLN A195-64.16925.3331.2911.0019.42O

Atom 2713N ARG A196-63.34523.418.4431.0018.90N

Atom 2714 CA ARG A196-64.57722.685.6631.0018.68C

Atom 2716 CB ARG A196-64.35621.186.4541.0018.53C

Atom 2719 CG ARG A196-64.85120.644-. 8881.0018.31C

Atom 2722 CD ARG A196-64.70521.622-2.0371.0017.93C

Atom 2725 NE ARG A196-65.93021.720-2.8341.0018.52N

Atom 2727 CZ ARG A196-66.48022.857-3.2561.0018.63C

Atom 2728 NH1 ARG A196-65.93824.014-2.9371.0019.84N

Atom 2731 NH2 ARG A196-67.58222.844-3.9991.0018.53N

Atom 2734C ARG A196-65.07022.9822.0611.0019.02C

Atom 2735O ARG A196-66.27623.0852.2841.0019.30O

Atom 2737N LEU A197-64.12723.1522.9901.0019.09N

Atom 2738 CA LEU A197-64.44423.4324.3791.0019.19C

Atom 2740 CB LEU A197-63.20323.3465.2621.0019.14C

Atom 2743 CG LEU A197-63.13522.0976.1301.0019.99C

Atom 2745 CD1 LEU A197-64.47621.8996.8111.0021.56C

Atom 2749 CD2 LEU A197-62.01622.1987.1611.0020.06C

Atom 2753C LEU A197-65.07124.7814.5531.0019.52C

Atom 2754O LEU A197-66.05224.9025.2521.0019.85O

Atom 2756N GLU A198-64.48825.8033.9411.0020.11N

Atom 2757 CA GLU A198-65.05127.1473.9861.0020.47C

Atom 2759 CB GLU A198-64.07928.1563.3851.0020.84C

Atom 2762 CG GLU A198-64.65929.5393.0691.0022.30C

Atom 2765 CD GLU A198-65.20630.2604.2831.0024.40C

Atom 2766 OE1 GLU A198-64.85229.8945.4181.0025.34O

Atom 2767 OE2 GLU A198-65.99131.2174.1061.0026.83O

Atom 2768C GLU A198-66.36027.1863.2261.0020.57C

Atom 2769O GLU A198-67.21228.0093.5291.0020.65O

Atom 2771N ALA A199-66.51926.2982.2401.0020.76N

Atom 2772 CA ALA A199-67.75126.2291.4521.0020.52C

Atom 2774 CB ALA A199-67.52125.492.1661.0020.44C

Atom 2778C ALA A199-68.90725.6112.2321.0020.55C

Atom 2779O ALA A199-69.98826.1582.2021.0020.17O

Atom 2781N VAL A200-68.70124.4932.9331.0021.10N

Atom 2782 CA VAL A200-69.79123.9353.7741.0021.51C

Atom 2784 CB VAL A200-69.50922.5764.4851.0021.18C

Atom 2786 CG1 VAL A200-69.61821.4603.5251.0021.27C

Atom 2790 CG2 VAL A200-68.16122.5695.2001.0021.23C

Atom 2794C VAL A200-70.17024.9054.8601.0021.99C

Atom 2795O VAL A200-71.33825.0225.1861.0022.99O

Atom 2797N TRP A201-69.20425.5905.4401.0022.10N

Atom 2798 CA TRP A201-69.55126.5656.4331.0022.58C

Atom 2800 CB TRP A201-68.31527.1447.1211.0022.92C

Atom 2803 CG TRP A201-68.66727.9578.3101.0023.65C

Atom 2804 CD1 TRP A201-68.75827.5209.5881.0025.08C

Atom 2806 NE1 TRP A201-69.12728.54910.4171.0026.35N

Atom 2808 CE2 TRP A201-69.29029.6839.6691.0025.48C

Atom 2809 CD2 TRP A201-69.01029.3448.3321.0024.77C

Atom 2810 CE3 TRP A201-69.09530.3367.3551.0024.92C

Atom 2812 CZ3 TRP A201-69.45031.6167.7391.0024.96C

Atom 2814 CH2 TRP A201-69.72031.9189.0781.0025.08C

Atom 2816 CZ2 TRP A201-69.64830.96810.0561.0024.68C

Atom 2818C TRP A201-70.35127.6625.7581.0022.71C

Atom 2819O TRP A201-71.48227.9216.1401.0022.76O

Atom 2821N SER A202-69.77628.2724.7271.0023.04N

Atom 2822 CA SER A202-70.33529.5004.1651.0023.29C

Atom 2824 CB SER A202-69.30430.2053.2901.0023.20C

Atom 2827 OG SER A202-68.30630.8074.1111.0023.07O

Atom 2829C SER A202-71.66629.3413.4321.0023.66C

Atom 2830O SER A202-72.39230.3103.2651.0023.38O

Atom 2832N ILE A203-71.99628.1243.0161.0024.49N

Atom 2833 CA ILE A203-73.32127.8592.4601.0025.07C

Atom 2835 CB ILE A203-73.39126.5301.6531.0024.74C

Atom 2837 CG1 ILE A203-72.49426.587.4231.0024.36C

Atom 2840 CD1 ILE A203-72.34425.255-. 2811.0023.81C

Atom 2844 CG2 ILE A203-74.79526.2921.1561.0024.45C

Atom 2848C ILE A203-74.33827.8583.6071.0025.91C

Atom 2849O ILE A203-75.35028.5543.5461.0026.26O

Atom 2851N GLU A204-74.05127.1044.6621.0026.69N

Atom 2852 CA GLU A204-74.92927.0535.8241.0027.40C

Atom 2854 CB GLU A204-74.28626.2176.9311.0027.65C

Atom 2857 CG GLU A204-75.13226.0328.1831.0029.02C

Atom 2860 CD GLU A204-76.53025.4917.9031.0030.44C

Atom 2861 OE1 GLU A204-76.74624.8586.8441.0031.22O

Atom 2862 OE2 GLU A204-77.41725.7038.7531.0031.96O

Atom 2863C GLU A204-75.25828.4516.3421.0027.61C

Atom 2864O GLU A204-76.40928.7786.5261.0027.78O

Atom 2866N ALA A205-74.24029.2746.5471.0028.15N

Atom 2867 CA ALA A205-74.41630.6377.0501.0028.41C

Atom 2869 CB ALA A205-73.06231.2857.2741.0028.41C

Atom 2873C ALA A205-75.23431.5206.1361.0028.84C

Atom 2874O ALA A205-76.05032.3026.6101.0028.54O

Atom 2876N TYR A206-74.97831.4084.8321.0029.84N

Atom 2877 CA TYR A206-75.58132.2813.8051.0030.41C

Atom 2879 CB TYR A206-74.80132.1702.4931.0030.20C

Atom 2882 CG TYR A206-75.18033.1731.4251.0029.62C

Atom 2883 CD1 TYR A206-74.72134.4821.4841.0030.32C

Atom 2885 CE1 TYR A206-75.04735.412.4891.0029.70C

Atom 2887 CZ TYR A206-75.83035.028-. 5781.0028.41C

Atom 2888 OH TYR A206-76.15535.956-1.5481.0026.74O

Atom 2890 CE2 TYR A206-76.29133.724-. 6591.0028.16C

Atom 2892 CD2 TYR A206-75.95832.806.3351.0028.39C

Atom 2894C TYR A206-77.03831.9183.5611.0031.15C

Atom 2895O TYR A206-77.85832.7813.2681.0031.30O

Atom 2897N ARG A207-77.34130.6313.6761.0032.05N

Atom 2898 CA ARG A207-78.69130.1283.5551.0032.81C

Atom 2900 CB ARG A207-78.68428.6233.8131.0032.86C

Atom 2903 CG ARG A207-80.02827.9413.6731.0034.01C

Atom 2906 CD ARG A207-80.06626.6324.4501.0035.11C

Atom 2909 NE ARG A207-79.09625.6693.9391.0035.35N

Atom 2911 CZ ARG A207-79.35324.7373.0221.0036.00C

Atom 2912 NH1 ARG A207-80.56224.6112.4781.0035.55N

Atom 2915 NH2 ARG A207-78.38123.9182.6401.0037.05N

Atom 2918C ARG A207-79.60930.8264.5501.0033.57C

Atom 2919O ARG A207-80.78331.0034.2631.0033.82O

Atom 2921N LYS A208-79.06431.2235.7071.0034.58N

Atom 2922 CA LYS A208-79.83531.8306.8121.0035.21C

Atom 2924 CB LYS A208-79.13731.5998.1591.0035.05C

Atom 2927 CG LYS A208-78.84730.1478.4961.0034.78C

Atom 2930 CD LYS A208-78.58329.9749.9801.0034.44C

Atom 2933 CE LYS A208-77.99228.61910.3091.0034.16C

Atom 2936 NZ LYS A208-76.54028.69310.5721.0033.81N

Atom 2940C LYS A208-80.07533.3336.6631.0036.06C

Atom 2941O LYS A208-81.03233.8577.2261.0036.19O

Atom 2943N LYS A209-79.19734.0325.9461.0036.93N

Atom 2944 CA LYS A209-79.41235.4455.6521.0037.77C

Atom 2946 CB LYS A209-78.28435.9984.7791.0038.18C

Atom 2949 CG LYS A209-76.92836.1345.4581.0039.90C

Atom 2952 CD LYS A209-75.98237.0234.6211.0042.39C

Atom 2955 CE LYS A209-74.53137.0165.1691.0044.21C

Atom 2958 NZ LYS A209-74.35037.6886.5091.0044.75N

Atoms 2962C LYS A209-80.73835.6004.9111.0037.89C

Atom 2963O LYS A209-81.04934.7854.0361.0038.20O

Atom 2965N GLU A210-81.51836.6325.2431.0037.87N

Atom 2966 CA GLU A210-82.84736.7974.6301.0037.72C

Atom 2968 CB GLU A210-83.82137.5785.5491.0038.19C

Atom 2971 CG GLU A210-83.85039.1305.4041.0039.68C

Atom 2974 CD GLU A210-85.27039.7365.5341.0041.27C

Atom 2975 OE1 GLU A210-86.17239.1006.1361.0041.67O

Atom 2976 OE2 GLU A210-85.48240.8595.0191.0042.17O

Atoms 2977C GLU A210-82.76037.3943.2191.0036.68C

Atom 2978O GLU A210-83.60537.1032.3711.0036.39O

Atom 2980N ASP A211-81.72538.1982.9691.0035.65N

Atom 2981 CA ASP A211-81.48138.7771.6321.0034.94C

Atom 2983 CB ASP A211-81.06440.2571.7401.0035.22C

Atom 2986 CG ASP A211-79.81140.4772.5991.0035.84C

Atom 2987 OD1 ASP A211-79.37939.5573.3411.0035.60O

Atom 2988 OD2 ASP A211-79.27641.6062.5361.0036.73O

Atom 2989C ASP A211-80.45137.989.8111.0033.73C

Atom 2990O ASP A211-79.75338.556-. 0211.0033.40O

Atom 2992N ALA A212-80.36636.6821.0571.0032.53N

Atom 2993 CA ALA A212-79.50635.783.2931.0031.40C

Atom 2995 CB ALA A212-79.56934.382.8891.0030.79C

Atom 2999C ALA A212-79.94035.762-1.1761.0030.60C

Atom 3000O ALA A212-81.12435.594-1.4671.0030.37O

Atoms 3002N ASN A213-79.00035.967-2.0971.0029.71N

Atom 3003 CA ASN A213-79.30435.809-3.5201.0029.27C

Atom 3005 CB ASN A213-78.14436.315-4.4021.0029.30C

Atom 3008 CG ASN A213-78.44236.217-5.9111.0029.07C

Atom 3009 OD1 ASN A213-78.43737.215-6.6241.0029.38O

Atom 3010 ND2 ASN A213-78.69135.015-6.3891.0028.37N

Atom 3013C ASN A213-79.63434.328-3.7851.0028.81C

Atom 3014O ASN A213-78.78433.455-3.6581.0029.04O

Atom 3016N GLN A214-80.88034.053-4.1451.0028.04N

Atom 3017 CA GLN A214-81.37632.692-4.1911.0027.32C

Atom 3019 CB GLN A214-82.90632.700-4.1781.0027.47C

Atom 3022 CG GLN A214-83.50533.269-2.8891.0027.68C

Atom 3025 CD GLN A214-83.29432.359-1.6881.0027.54C

Atom 3026 OE1 GLN A214-83.94031.320-1.5711.0028.19O

Atom 3027 NE2 GLN A214-82.39232.748-. 7901.0026.90N

Atom 3030C GLN A214-80.85831.902-5.3851.0026.71C

Atom 3031O GLN A214-80.86330.668-5.3551.0026.91O

Atom 3033N VAL A215-80.43932.600-6.4421.0025.81N

Atom 3034 CA VAL A215-79.78931.947-7.5881.0024.88C

Atom 3036 CB VAL A215-79.65132.894-8.8081.0024.81C

Atom 3038 CG1 VAL A215-78.45932.483-9.6801.0024.94C

Atom 3042 CG2 VAL A215-80.93532.907-9.6201.0023.74C

Atom 3046C VAL A215-78.41531.427-7.1761.0024.18C

Atom 3047O VAL A215-78.07330.282-7.4301.0023.74O

Atom 3049N LEU A216-77.65032.283-6.5101.0023.78N

Atom 3050 CA LEU A216-76.29931.961-6.0361.0023.33C

Atom 3052 CB LEU A216-75.68033.195-5.3731.0023.10C

Atom 3055 CG LEU A216-74.19433.192-5.0591.0022.91C

Atom 3057 CD1 LEU A216-73.38332.962-6.3121.0022.88C

Atom 3061 CD2 LEU A216-73.82634.518-4.4241.0022.03C

Atom 3065C LEU A216-76.33330.797-5.0501.0022.92C

Atom 3066O LEU A216-75.59829.826-5.2011.0023.38O

Atom 3068N LEU A217-77.21430.890-4.0601.0022.09N

Atom 3069 CA LEU A217-77.36729.851-3.0541.0021.14C

Atom 3071 CB LEU A217-78.48830.225-2.0901.0021.11C

Atom 3074 CG LEU A217-78.78229.236-. 9611.0021.08C

Atom 3076 CD1 LEU A217-77.70329.267.1011.0019.87C

Atom 3080 CD2 LEU A217-80.14629.535-. 3601.0021.46C

Atoms 3084C LEU A217-77.68228.517-3.6851.0020.38C

Atom 3085O LEU A217-77.13327.508-3.2861.0020.04O

Atom 3087N GLU A218-78.57928.512-4.6611.0019.97N

Atom 3088 CA GLU A218-79.02727.260-5.2731.0019.72C

Atom 3090 CB GLU A218-80.22027.499-6.2121.0019.87C

Atom 3093 CG GLU A218-81.00526.228-6.6271.0021.03C

Atom 3096 CD GLU A218-82.30326.535-7.4241.0022.59C

Atom 3097 OE1 GLU A218-82.64327.730-7.6191.0023.61O

Atom 3098 OE2 GLU A218-82.98325.578-7.8631.0022.31O

Atom 3099C GLU A218-77.85426.613-6.0091.0019.03C

Atom 3100O GLU A218-77.52225.452-5.7641.0018.97O

Atom 3102N LEU A219-77.20327.381-6.8781.0018.06N

Atom 3103 CA LEU A219-76.01226.907-7.5731.0017.15C

Atom 3105 CB LEU A219-75.43928.029-8.4181.0016.75C

Atom 3108 CG LEU A219-74.19627.717-9.2311.0016.01C

Atom 3110 CD1 LEU A219-74.51126.832-10.4041.0012.99C

Atom 3114 CD2 LEU A219-73.57729.028-9.6751.0016.20C

Atom 3118C LEU A219-74.97326.409-6.5701.0016.75C

Atom 3119O LEU A219-74.37725.355-6.7571.0016.47O

Atom 3121N ALA A220-74.78627.169-5.4961.0016.40N

Atom 3122 CA ALA A220-73.85826.808-4.4221.0016.15C

Atom 3124 CB ALA A220-73.90627.830-3.3021.0016.13C

Atom 3128C ALA A220-74.13725.436-3.8621.0016.03C

Atom 3129O ALA A220-73.25324.603-3.7991.0016.30O

Atom 3131N ILE A221-75.37125.201-3.4471.0016.24N

Atom 3132 CA ILE A221-75.73123.916-2.8571.0016.33C

Atom 3134 CB ILE A221-77.20323.895-2.3521.0015.94C

Atom 3136 CG1 ILE A221-77.41024.879-1.2031.0015.36C

Atom 3139 CD1 ILE A221-78.84225.234-. 9621.0014.49C

Atom 3143 CG2 ILE A221-77.57122.537-1.8361.0015.18C

Atom 3147C ILE A221-75.50922.841-3.9111.0017.06C

Atom 3148O ILE A221-74.89921.819-3.6531.0016.51O

Atom 3150N LEU A222-75.98123.138-5.1171.0018.53N

Atom 3151 CA LEU A222-76.00622.207-6.2431.0019.25C

Atom 3153 CB LEU A222-76.65722.891-7.4451.0019.18C

Atom 3156 CG LEU A222-77.03721.972-8.5971.0019.65C

Atom 3158 CD1 LEU A222-78.31822.489-9.2681.0019.24C

Atom 3162 CD2 LEU A222-75.86921.788-9.5971.0018.75C

Atom 3166C LEU A222-74.61821.751-6.6301.0020.07C

Atom 3167O LEU A222-74.38120.558-6.7781.0020.55O

Atom 3169N ASP A223-73.71022.711-6.7971.0020.92N

Atom 3170 CA ASP A223-72.33022.427-7.1891.0021.43C

Atom 3172 CB ASP A223-71.62123.723-7.5851.0021.63C

Atom 3175 CG ASP A223-70.20223.495-8.0701.0022.51C

Atom 3176 OD1 ASP A223-69.29623.282-7.2251.0024.67O

Atom 3177 OD2 ASP A223-69.99023.544-9.2961.0022.73O

Atom 3178C ASP A223-71.57321.722-6.0601.0021.79C

Atom 3179O ASP A223-70.84320.764-6.3131.0021.73O

Atom 3181N TYR A224-71.75522.182-4.8201.0022.14N

Atom 3182 CA TYRA 224-71.12021.529-3.6861.0022.22C

Atom 3184 CB TYR A224-71.46222.190-2.3551.0022.38C

Atom 3187 CG TYR A224-70.67321.542-1.2491.0022.65C

Atom 3188 CD1 TYR A224-69.35621.864-1.0531.0022.59C

Atom 3190 CE1 TYR A224-68.62221.258-. 0981.0023.38C

Atom 3192 CZ TYR A224-69.17720.288.6701.0023.22C

Atom 3193 OH TYR A224-68.40219.6841.6201.0023.93O

Atom 3195 CE2 TYR A224-70.48319.931.5001.0023.36C

Atom 3197 CD2 TYR A224-71.22120.547-. 4641.0023.41C

Atom 3199C TYR A224-71.48520.065-3.6051.0022.52C

Atom 3200O TYR A224-70.64119.233-3.3111.0022.93O

Atom 3202N ASN A225-72.74219.749-3.8561.0022.94N

Atom 3203 CA ASN A225-73.18718.374-3.8011.0023.44C

Atom 3205 CB ASN A225-74.70618.310-3.7291.0023.34C

Atom 3208 CG ASN A225-75.21018.579-2.3521.0022.62C

Atom 3209 OD1 ASN A225-74.74917.977-1.4071.0023.33O

Atom 3210 ND2 ASN A225-76.14619.494-2.2231.0022.52N

Atom 3213C ASN A225-72.69417.523-4.9591.0024.26C

Atom 3214O ASN A225-72.40816.328-4.7671.0024.88O

Atom 3216N MET A226-72.60718.119-6.1501.0024.67N

Atom 3217 CA MET A226-72.16717.395-7.3491.0024.95C

Atom 3219 CB MET A226-72.42118.237-8.5941.0025.37C

Atom 3222 CG MET A226-71.78517.713-9.8731.0027.23C

Atom 3225 SD MET A226-70.83719.010-10.7081.0031.73S

Atom 3226 CE MET A226-72.18520.000-11.3671.0031.30C

Atom 3230C MET A226-70.68817.045-7.2471.0024.70C

Atom 3231O MET A226-70.29115.929-7.5681.0024.91O

Atom 3233N ILE A227-69.87317.995-6.7991.0024.43N

Atom 3234 CA ILE A227-68.45617.726-6.5981.0024.18C

Atom 3236 CB ILE A227-67.65618.971-6.1541.0024.15C

Atom 3238 CG1 ILE A227-67.62820.021-7.2531.0023.64C

Atom 3241 CD1 ILE A227-66.85321.246-6.8801.0023.11C

Atom 3245 CG2 ILE A227-66.22918.603-5.8271.0024.36C

Atom 3249C ILE A227-68.32916.645-5.5461.0023.98C

Atom 3250O ILE A227-67.60915.689-5.7471.0024.35O

Atom 3252N GLN A228-69.04816.779-4.4391.0023.79N

Atom 3253 CA GLN A228-69.02015.754-3.3821.0023.66C

Atom 3255 CB GLN A228-70.07716.010-2.3051.0023.64C

Atom 3258 CG GLN A228-69.97215.049-1.1451.0022.91C

Atom 3261 CD GLN A228-70.89115.417-. 0331.0023.26C

Atom 3262 OE1 GLN A228-72.08215.098-. 0691.0025.64O

Atom 3263 NE2 GLN A228-70.35716.083.9781.0021.77N

Atom 3266C GLN A228-69.24314.349-3.8931.0023.54C

Atom 3267O GLN A228-68.66413.412-3.3571.0023.59O

Atom 3269N SER A229-70.10514.194-4.8931.0023.27N

Atom 3270 CA SER A229-70.39412.868-5.4061.0023.35C

Atom 3272 CB SER A229-71.75312.812-6.0951.0023.31C

Atom 3275 OG SER A229-71.83613.823-7.0601.0024.31O

Atom 3277C SER A229-69.28712.394-63311.0023.19C

Atom 3278O SER A229-69.13011.194-6.5121.0023.44O

Atom 3280N VAL A230-68.51213.306-6.9141.0023.14N

Atom 3281 CA VAL A230-67.26912.874-7.5521.0023.00C

Atom 3283 CB VAL A230-66.46913.998-8.2531.0022.75C

Atom 3285 CG1 VAL A230-65.09113.470-8.6671.0021.87C

Atom 3289 CG2 VAL A230-67.22214.539-9.4591.0021.74C

Atom 3293C VAL A230-66.41712.268-6.4521.0023.35C

Atom 3294O VAL A230-65.91711.173-6.5891.0023.68O

Atom 3296N TYR A231-66.28412.968-5.3401.0023.96N

Atom 3297 CA TYR A231-65.41412.509-4.2741.0024.60C

Atom 3299 CB TYR A231-65.48613.426-3.0511.0024.69C

Atom 3302 CG TYR A231-64.96314.837-3.2111.0024.11C

Atom 3303 CD1 TYR A231-64.07115.190-4.2141.0024.31C

Atom 3305 CE1 TYR A231-63.59216.491-4.3221.0024.63C

Atom 3307 CZ TYR A231-63.99417.441-3.4061.0025.13C

Atom 3308 OH TYR A231-63.55418.754-3.4561.0024.64O

Atom 3310 CE2 TYR A231-64.86317.086-2.4021.0025.76C

Atom 3312 CD2 TYR A231-65.32915.800-2.3081.0024.28C

Atom 3314C TYR A231-65.78511.111-3.8331.0025.26C

Atom 3315O TYR A231-64.91710.315-3.4881.0025.44O

Atom 3317N GLN A232-67.07910.819-3.8331.0026.04N

Atom 3318 CA GLN A232-67.5669.532-3.3621.0026.57C

Atom 3320 CB GLN A232-69.0609.621-3.0571.0026.44C

Atom 3323 CG GLN A232-69.33910.397-1.7781.0026.25C

Atom 3326 CD GLN A232-70.78610.819-1.6301.0026.53C

Atom 3327 OE1 GLN A232-71.66710.305-2.3181.0027.77O

Atom 3328 NE2 GLN A232-71.04011.759-. 7231.0025.51N

Atom 3331C GLN A232-67.2388.414-4.3511.0027.44C

Atom 3332O GLN A232-66.8527.319-3.9351.0027.33O

Atom 3334N ARG A233-67.3738.691-5.6491.0028.66N

Atom 3335 CA ARG A233-66.9057.768-6.6851.0029.86C

Atom 3337 CB ARG A233-67.2128.292-8.0901.0030.08C

Atom 3340 CG ARG A233-66.3787.634-9.1791.0032.80C

Atom 3343 CD ARG A233-66.9137.923-10.5721.0036.74C

Atom 3346 NE ARG A233-66.9629.363-10.8601.0040.33N

Atom 3348 CZ ARG A233-68.06910.119-10.8911.0043.12C

Atom 3349 NH1 ARG A233-69.2769.600-10.6551.0044.55N

Atom 3352 NH2 ARG A233-67.97111.418-11.1691.0043.38N

Atom 3355C ARG A233-65.4017.518-6.5141.0030.34C

Atom 3356O ARG A233-64.9626.374-6.4121.0030.55O

Atom 3358N ASP A234-64.6218.591-6.4611.0031.00N

Atom 3359 CA ASP A234-63.1878.487-6.2051.0031.48C

Atom 3361 CB ASP A234-62.5949.870-5.9421.0031.56C

Atom 3364 CG ASP A234-62.57310.741-7.1671.0032.78C

Atom 3365 OD1 ASP A234-62.91110.249-8.2761.0034.25O

Atom 3366 OD2 ASP A234-62.21511.930-7.0111.0034.81O

Atom 3367C ASP A234-62.8857.596-5.0101.0031.70C

Atom 3368O ASP A234-61.9856.780-5.0531.0031.56O

Atom 3370N LEU A235-63.6477.766-3.9431.0032.43N

Atom 3371 CA LEU A235-63.3667.102-2.6851.0033.04C

Atom 3373 CB LEU A235-64.0727.833-1.5531.0032.57C

Atom 3376 CG LEU A235-63.8847.252-. 1671.0030.85C

Atom 3378 CD1 LEU A235-62.4287.261.1741.0028.78C

Atom 3382 CD2 LEU A235-64.7038.050.8231.0029.93C

Atom 3386C LEU A235-63.7895.637-2.6861.0034.69C

Atom 3387O LEU A235-63.1234.812-2.0651.0035.29O

Atom 3389N ARG A236-64.8935.299-3.3541.0036.09N

Atom 3390 CA ARG A236-65.2903.893-3.4581.0037.26C

Atom 3392 CB ARG A236-66.6723.736-4.1031.0037.64C

Atom 3395 CG ARG A236-67.8394.000-3.1571.0039.15C

Atom 3398 CD ARG A236-69.1623.528-3.7411.0040.25C

Atom 3401 NE ARG A236-69.3854.046-5.0951.0041.64N

Atom 3403 CZ ARG A236-69.8375.269-5.3921.0042.54C

Atom 3404 NH1 ARG A236-70.1156.147-4.4301.0042.18N

Atom 3407 NH2 ARG A236-70.0125.621-6.6681.0043.04N

Atom 3410C ARG A236-64.2663.108-4.2621.0037.81C

Atom 3411O ARG A236-64.1041.912-4.0601.0038.07O

Atom 3413N GLU A237-63.5843.801-5.1681.0038.69N

Atom 3414 CA GLU A237-62.6393.189-6.1021.0039.45C

Atom 3416 CB GLU A237-62.4524.108-7.3381.0040.25C

Atom 3419 CG GLU A237-62.2683.387-8.7101.0043.02C

Atom 3422 CD GLU A237-60.8353.458-9.2871.0046.64C

Atom 3423 OE1 GLU A237-60.0934.440-8.9971.0048.03O

Atom 3424 OE2 GLU A237-60.4662.519-10.0471.0048.35O

Atom 3425C GLU A237-61.3102.905-5.4081.0038.70C

Atom 3426O GLU A237-60.8321.782-5.4401.0038.33O

Atom 3428N THR A238-60.7263.908-4.7641.0038.40N

Atom 3429 CA THR A238-59.5043.669-4.0091.0038.74C

Atom 3431 CB THR A238-58.7104.965-3.5931.0038.78C

Atom 3433 OG1 THR A238-59.2945.583-2.4441.0038.38O

Atom 3435 CG2 THR A238-58.6125.963-4.7431.0038.94C

Atom 3439C THR A238-59.8022.834-2.7731.0039.05C

Atom 3440O THR A238-58.8862.294-2.1531.0039.17O

Atom 3442N SER A239-61.0762.717-2.4081.0039.34N

Atom 3443 CA SER A239-61.4431.841-1.3041.0039.47C

Atom 3445 CB SER A239-62.8442.149-. 7921.0039.34C

Atom 3448 OG SER A239-63.0871.428.3961.0039.94O

Atom 3450C SER A239-61.313.367-1.6991.0039.53C

Atom 3451O SER A239-60.834-. 439-. 9001.0039.53O

Atom 3453N ARG A240-61.728.021-2.9211.0039.69N

Atom 3454 CA ARG A240-61.559-1.341-3.4391.0039.79C

Atom 3456 CB ARG A240-62.105-1.492-4.8671.0040.34C

Atom 3459 CG ARG A240-63.624-1.715-4.9471.0043.03C

Atom 3462 CD ARG A240-64.104-2.125-6.3641.0046.66C

Atom 3465 NE ARG A240-63.780-1.136-7.4161.0050.46N

Atom 3467 CZ ARG A240-64.535-., 082-7.7751.0053.13C

Atom 3468 NH1 ARG A240-64.112.732-8.7491.0053.13N

Atom 3471 NH2 ARG A240-65.707.178-7.1781.0054.02N

Atom 3474C ARG A240-60.089-1.704-3.4141.0038.94C

Atom 3475O ARG A240-59.732-2.795-2.9781.0039.09O

Atom 3477N TRP A241-59.246-. 775-3.8621.0037.92N

Atom 3478 CA TRP A241-57.787-., 947-3.8421.0036.93C

Atom 3480 CB TRP A241-57.099.318-4.3881.0036.57C

Atom 3483 CG TRP A241-55.624.333-4.2091.0034.71C

Atom 3484 CD1 TRP A241-54.702-., 312-4.9691.0033.50C

Atom 3486 NE1 TRP A241-53.441-., 068-4.4821.0032.62N

Atom 3488 CE2 TRP A241-53.538.747-3.3921.0031.16C

Atom 3489 CD2 TRP A241-54.8961.022-3.1911.0032.61C

Atom 3490 CE3 TRP A241-55.2681.837-2.1171.0032.63C

Atom 3492 CZ3 TRP A241-54.2932.345-1.3071.0031.31C

Atom 3494 CH2 TRP A241-52.9562.053-1.5371.0031.81C

Atom 3496 CZ2 TRP A241-52.5601.252-2.5771.0031.18C

Atom 3498C TRP A241-57.263-1.274-2.4441.0036.67C

Atom 3499O TRP A241-56.540-2.247-2.2521.0036.32O

Atom 3501N TRP A242-57.647-,. 460-1.4711.0036.59N

Atom 3502 CA TRP A242-57.150-. 593-. 1001.0036.80C

Atom 3504 CB TRP A242-57.694.582.7341.0036.47C

Atom 3507 CG TRP A242-57.113.7542.1071.0035.59C

Atom 3508 CD1 TRP A242-57.806.8313.2701.0035.14C

Atom 3510 NE1 TRP A242-56.950.9994.3281.0034.47N

Atom 3512 CE2 TRP A242-55.6671.0323.8591.0034.64C

Atom 3513 CD2 TRP A242-55.728.8842.4611.0035.26C

Atom 3514 CE3 TRP A242-54.531.8821.7321.0035.22C

Atom 3516 CZ3 TRP A242-53.3421.0242.4091.0034.30C

Atom 3518 CH2 TRP A242-53.3181.1693.7991.0034.70C

Atom 3520 CZ2 TRP A242-54.4671.1734.5421.0034.63C

Atom 3522C TRP A242-57.482-1.975.5241.0037.34C

Atom 3523O TRP A242-56.628-2.6231.1261.0036.53O

Atom 3525N ARG A243-58.720-2.421.3481.0038.54N

Atom 3526 CA ARG A243-59.149-3.734.8221.0039.71C

Atom 3528 CB ARG A243-60.669-3.896.6871.0040.10C

Atom 3531 CG ARG A243-61.495-3.1341.7471.0042.18C

Atom 3534 CD ARG A243-62.826-2.6231.1691.0045.18C

Atom 3537 NE ARG A243-63.506-3.656.3691.0048.22N

Atom 3539 CZ ARG A243-64.374-3.431-. 6291.0049.95C

Atom 3540 NH1 ARG A243-64.717-2.182-. 9911.0050.13N

Atom 3543 NH2 ARG A243-64.911-4.477-1.2731.0049.77N

Atom 3546C ARG A243-58.438-4.852.0681.0040.08C

Atom 3547O ARG A243-58.084-5.870.6651.0040.45O

Atom 3549N ARG A244-58.236-4.663-1.2361.0040.42N

Atom 3550 CA ARG A244-57.499-5.621-2.0631.0040.65C

Atom 3552 CB ARG A244-57.370-5.100-3.5031.0041.29C

Atom 3555 CG ARG A244-56.939-6.126-4.5601.0043.27C

Atoms 3558 CD ARG A244-58.090-7.062-4.9521.0046.01C

Atom 3561 NE ARG A244-57.595-8.337-5.4851.0048.77N

Atom 3563 CZ ARG A244-57.075-9.332-4.7521.0051.17C

Atom 3564 NH1 ARG A244-56.968-9.234-3.4221.0051.63N

Atom 3567 NH2 ARG A244-56.656-10.448-5.3531.0052.11N

Atom 3570C ARG A244-56.120-5.861-1.4651.0040.12C

Atom 3571O ARG A244-55.728-7.000-1.2351.0039.96O

Atom 3573N VAL A245-55.399-4.778-1.2011.0039.78N

Atom 3574 CA VAL A245-54.099-4.858-. 5431.0039.68C

Atom 3576 CB VAL A245-53.430-3.458-. 4371.0039.70C

Atom 3578 CG1 VAL A245-53.133-2.914-1.8241.0039.54C

Atom 3582 CG2 VAL A245-52.145-3.507.3951.0039.41C

Atom 3586C VAL A245-54.262-5.472.8411.0039.73C

Atom 3587O VAL A245-53.455-6.2911.2531.0039.53O

Atom 3589N GLY A246-55.312-5.0511.5441.0040.11N

Atom 3590 CA GLY A246-55.705-5.6172.8391.0040.35C

Atom 3593C GLY A246-54.621-5.6483.8941.0040.58C

Atom 3594O GLY A246-54.396-6.6764.5101.0040.68O

Atoms 3596N LEU A247-53.963-4.5224.1291.0041.15N

Atom 3597 CA LEU A247-52.778-4.5194.9821.0041.71C

Atom 3599 CB LEU A247-51.808-3.4224.5371.0041.60C

Atom 3602 CG LEU A247-50.334-3.8154.4411.0040.83C

Atom 3604 CD1 LEU A247-50.158-5.0143.5391.0040.54C

Atom 3608 CD2 LEU A247-49.534-2.6443.9181.0039.92C

Atoms 3612C LEU A247-53.136-4.3856.4711.0042.60C

Atom 3613O LEU A247-52.588-5.1117.3131.0042.06O

Atom 3615N ALA A248-54.064-3.4756.7881.0043.75N

Atom 3616 CA ALA A248-54.603-3.3528.1621.0044.52C

Atom 3618 CB ALA A248-55.712-2.2968.2101.0044.31C

Atom 3622C ALA A248-55.129-4.7068.6951.0045.10C

Atom 3623O ALA A248-54.969-5.0419.8751.0044.96O

Atom 3625N THR A249-55.742-5.4777.8021.0045.91N

Atom 3626 CA THR A249-56.328-6.7688.1541.0046.50C

Atom 3628 CB THR A249-57.303-7.2777.0411.0046.48C

Atom 3630 OG1 THR A249-56.583-8.0396.0631.0046.20O

Atom 3632 CG2 THR A249-58.033-6.1026.3501.0046.70C

Atom 3636C THR A249-55.257-7.8408.4471.0047.06C

Atom 3637O THR A249-55.531-8.8139.1591.0047.22O

Atom 3639N LYS A250-54.049-7.6617.9051.0047.52N

Atom 3640 CA LYS A250-52.952-8.6208.0961.0047.91C

Atom 3642 CB LYS A250-52.319-8.9766.7441.0048.09C

Atom 3645 CG LYS A250-52.911-10.2296.0881.0048.91C

Atom 3648 CD LYS A250-52.210-11.5106.5851.0049.88C

Atom 3651 CE LYS A250-53.066-12.7606.3491.0050.12C

Atom 3654 NZ LYS A250-52.385-14.0116.7911.0049.99N

Atom 3658C LYS A250-51.880-8.1299.0781.0048.13C

Atom 3659O LYS A250-51.252-8.9399.7591.0047.89O

Atoms 3661N LEU A251-51.667-6.8129.1341.0048.63N

Atom 3662 CA LEU A251-50.758-6.18710.1141.0048.83C

Atom 3664 CB LEU A251-49.981-5.0209.4851.0048.74C

Atom 3667 CG LEU A251-48.569-5.2968.9601.0048.51C

Atom 3669 CD1 LEU A251-48.472-6.5948.1741.0047.96C

Atom 3673 CD2 LEU A251-48.102-4.1158.1161.0048.76C

Atoms 3677C LEU A251-51.559-5.70311.3241.0049.17C

Atom 3678O LEU A251-52.176-4.63211.3041.0049.28O

Atom 3680N HIS A252-51.521-6.48612.3931.0049.53N

Atom 3681 CA HIS A252-52.470-6.32213.4941.0050.02C

Atom 3683 CB HIS A252-52.598-7.64714.2661.0050.42C

Atom 3686 CG HIS A252-52.860-8.83413.3801.0052.23C

Atom 3687 ND1 HIS A252-54.032-8.98912.6671.0053.75N

Atom 3689 CE1 HIS A252-53.978-10.11311.9731.0054.43C

Atom 3691 NE2 HIS A252-52.810-10.68912.2011.0054.52N

Atom 3693 CD2 HIS A252-52.090-9.91013.0771.0053.70C

Atom 3695C HIS A252-52.161-5.14714.4411.0049.64C

Atom 3696O HIS A252-52.951-4.84915.3361.0049.61O

Atom 3698N PHE A253-51.027-4.48314.2291.0049.37N

Atom 3699 CA PHE A253-50.652-3.27314.9731.0049.15C

Atoms 3701 CB PHE A253-49.144-3.27315.2601.0049.07C

Atom 3704 CG PHE A253-48.307-3.11214.0251.0048.30C

Atom 3705 CD1 PHE A253-48.028-1.85113.5181.0048.10C

Atom 3707 CE1 PHE A253-47.290-1.70212.3491.0048.21C

Atom 3709 CZ PHE A253-46.825-2.82511.6751.0047.88C

Atom 3711 CE2 PHE A253-47.101-4.09012.1751.0047.66C

Atom 3713 CD2 PHE A253-47.842-4.22613.3381.0047.74C

Atom 3715C PHE A253-50.974-2.00614.1761.0049.31C

Atom 3716O PHE A253-50.846-. 89314.7021.0049.01O

Atom 3718N ALA A254-51.365-2.18512.9101.0049.48N

Atom 3719 CA ALA A254-51.412-1.09511.9311.0049.63C

Atom 3721 CB ALA A254-51.344-1.66310.5241.0049.64C

Atom 3725C ALA A254-52.650-. 22412.0611.0049.77C

Atom 3726O ALA A254-53.761-. 73512.2191.0049.86O

Atom 3728N ARG A255-52.4521.09011.9751.0049.93N

Atom 3729 CA ARG A255-53.5622.04211.9081.0050.27C

Atom 3731 CB ARG A255-53.0943.46812.2371.0050.43C

Atom 3734 CG ARG A255-52.6783.73613.6961.0050.82C

Atom 3737 CD ARG A255-52.2425.21113.8871.0051.32C

Atom 3740 NE ARG A255-51.0035.52213.1551.0051.81N

Atom 3742 CZ ARG A255-50.5716.74612.8291.0051.67C

Atom 3743 NH1 ARG A255-51.2647.83913.1461.0051.63N

Atom 3746 NH2 ARG A255-49.4276.87712.1621.0051.52N

Atom 3749C ARG A255-54.1602.04010.4971.0050.32C

Atom 3750O ARG A255-53.4162.0819.5041.0050.35O

Atom 3752N ASP A256-55.4922.00510.4121.0050.17N

Atom 3753 CA ASP A256-56.1902.0909.1281.0050.18C

Atom 3755 CB ASP A256-57.2591.0099.0371.0050.37C

Atom 3758 CG ASP A256-58.0951.1307.7801.0050.96C

Atom 3759 OD1 ASP A256-59.2521.6017.8811.0052.00O

Atom 3760 OD2 ASP A256-57.581.7876.6931.0050.94O

Atom 3761C ASP A256-56.8383.4708.9451.0049.85C

Atom 3762O ASP A256-57.8123.8049.6241.0050.13O

Atom 3764N ARG A257-56.3154.2638.0131.0049.11N

Atom 3765 CA ARG A257-56.7125.6657.9131.0048.59C

Atom 3767 CB ARG A257-55.6226.5538.5291.0048.79C

Atom 3770 CG ARG A257-55.3186.27510.0061.0049.85C

Atom 3773 CD ARG A257-56.5386.48010.9081.0051.01C

Atom 3776 NE ARG A257-56.1987.27412.0891.0051.80N

Atom 3778 CZ ARG A257-55.7796.79113.2601.0052.00C

Atom 3779 NH1 ARG A257-55.6435.48613.4681.0051.64N

Atom 3782 NH2 ARG A257-55.5017.63814.2451.0052.62N

Atom 3785C ARG A257-56.9886.1126.4771.0047.58C

Atom 3786O ARG A257-56.4767.1446.0311.0047.40O

Atom 3788N LEU A258-57.8145.3525.7611.0046.18N

Atom 3789 CA LEU A258-58.0945.6724.3581.0044.78C

Atom 3791 CB LEU A258-58.7774.5083.6291.0044.57C

Atom 3794 CG LEU A258-58.9174.7312.1211.0043.79C

Atom 3796 CD1 LEU A258-57.5574.6611.4781.0043.89C

Atom 3800 CD2 LEU A258-59.8503.7331.4921.0042.88C

Atom 3804C LEU A258-58.9706.9074.2591.0043.52C

Atom 3805O LEU A258-58.6437.8493.5451.0043.42O

Atom 3807N ILE A259-60.0806.8954.9831.0041.98N

Atom 3808 CA ILE A259-61.0727.9484.8431.0040.89C

Atom 3810 CB ILE A259-62.3497.7035.6931.0041.02C

Atom 3812 CG1 ILE A259-62.8466.2485.5701.0041.82C

Atom 3815 CD1 ILE A259-64.0295.8726.5081.0042.29C

Atom 3819 CG2 ILE A259-63.4468.6625.2621.0040.47C

Atom 3823C ILE A259-60.4249.2535.2731.0039.74C

Atom 3824O ILE A259-60.60710.2914.6351.0039.25O

Atom 3826N GLU A260-59.6509.1916.3551.0038.46N

Atom 3827 CA GLU A260-58.95110.3666.8461.0037.44C

Atom 3829 CB GLU A260-58.18310.0728.1401.0037.74C

Atom 3832 CG GLU A260-59.0419.9349.3931.0038.71C

Atom 3835 CD GLU A260-59.4698.5019.6931.0041.00C

Atom 3836 OE1 GLU A260-59.2737.5948.8421.0042.70O

Atom 3837 OE2 GLU A260-60.0128.28110.8001.0042.43O

Atom 3838C GLU A260-57.99510.8415.7641.0035.94C

Atom 3839O GLU A260-57.98112.0205.4181.0036.10O

Atom 3841N SER A261-57.2229.9085.2121.0034.02N

Atom 3842 CA SER A261-56.26310.2294.1521.0032.47C

Atom 3844 CB SER A261-55.4079.0153.7741.0032.51C

Atom 3847 OG SER A261-54.2538.9404.5841.0033.14O

Atom 3849C SER A261-56.89410.7642.8891.0030.82C

Atom 3850O SER A261-56.19911.3062.0621.0030.79O

Atom 3852N PHE A262-58.19410.5892.7131.0029.25N

Atom 3853 CA PHE A262-58.86111.0911.5141.0027.98C

Atom 3855 CB PHE A262-60.01110.1851.1191.0027.57C

Atom 3858 CG PHE A262-60.47310.423-. 2511.0026.11C

Atom 3859 CD1 PHE A262-59.7639.914-1.3181.0025.14C

Atom 3861 CE1 PHE A262-60.16910.147-2.6051.0024.32C

Atom 3863 CZ PHE A262-61.28410.917-2.8401.0024.36C

Atom 3865 CE2 PHE A262-61.98711.445-1.7851.0025.23C

Atom 3867 CD2 PHE A262-61.57511.201-. 4921.0025.61C

Atom 3869C PHE A262-59.39412.5071.7071.0027.29C

Atom 3870O PHE A262-59.27513.359.8211.0027.39O

Atom 3872N TYR A263-60.02512.7232.8561.0026.19N

Atom 3873 CA TYR A263-60.41514.0523.3101.0025.22C

Atom 3875 CB TYR A263-60.97513.9424.7351.0025.21C

Atom 3878 CG TYR A263-61.03715.1995.5781.0025.37C

Atom 3879 CD1 TYR A263-62.02016.1525.3851.0024.95C

Atom 3881 CE1 TYR A263-62.08417.2826.1971.0026.54C

Atom 3883 CZ TYR A263-61.15817.4557.2291.0027.44C

Atom 3884 OH TYR A263-61.18618.5678.0591.0028.97O

Atom 3886 CE2 TYR A263-60.18516.5127.4381.0027.10C

Atom 3888 CD2 TYR A263-60.13615.3906.6261.0026.91C

Atom 3890C TYR A263-59.19014.9463.2381.0024.29C

Atom 3891O TYR A263-59.26716.0772.7571.0024.13O

Atom 3893N TRP A264-58.05514.4153.6821.0023.01N

Atom 3894 CA TRP A264-56.78915.1213.5671.0022.32C

Atom 3896 CB TRP A264-55.64214.2614.1191.0022.26C

Atom 3899 CG TRP A264-54.32614.8743.8601.0022.16C

Atom 3900 CD1 TRP A264-53.61414.8212.6991.0022.68C

Atom 3902 NE1 TRP A264-52.45615.5382.8181.0023.08N

Atom 3904 CE2 TRP A264-52.40716.0834.0721.0023.07C

Atom 3905 CD2 TRP A264-53.57915.6864.7531.0022.18C

Atom 3906 CE3 TRP A264-53.78216.1196.0661.0022.57C

Atom 3908 CZ3 TRP A264-52.82416.9256.6571.0023.43C

Atom 3910 CH2 TRP A264-51.65617.2975.9551.0024.14C

Atom 3912 CZ2 TRP A264-51.43316.8864.6631.0023.64C

Atom 3914C TRP A264-56.48515.5232.1121.0021.50C

Atom 3915O TRP A264-56.17916.6821.8201.0021.29O

Atom 3917N ALA A265-56.56114.5471.2131.0020.41N

Atom 3918 CA ALA A265-56.24214.760-. 1871.0019.63C

Atom 3920 CB ALA A265-56.29813.437-9531.0019.39C

Atom 3924C ALA A265-57.17615.792-7981.0019.07C

Atom 3925O ALA A265-56.76016.573-1.6331.0018.99O

Atom 3927N VAL A266-58.43115.814-. 3591.0018.78N

Atom 3928 CA VAL A266-59.39616.828-. 8181.0018.56C

Atom 3930 CB VAL A266-60.83916.541-. 2781.0018.41C

Atom 3932 CG1 VAL A266-61.40515.298-. 9351.0018.88C

Atom 3936 CG2 VAL A266-61.78017.709-. 5051.0017.21C

Atom 3940C VAL A266-58.94718.257-. 4501.0018.43C

Atom 3941O VAL A266-59.25019.200-1.1711.0018.83O

Atom 3943N GLY A267-58.23018.411.6631.0017.96N

Atom 3944 CA GLY A267-57.71419.7121.0671.0017.45C

Atom 3947C GLY A267-56.68720.180.0701.0017.20C

Atom 3948O GLY A267-56.57421.365-. 2151.0017.41O

Atom 3950N VAL A268-55.95919.219-. 4801.0016.88N

Atom 3951 CA VAL A268-54.82219.487-1.3191.0016.62C

Atom 3953 CB VAL A268-53.83318.300-1.2901.0016.19C

Atom 3955 CG1 VAL A268-52.69118.536-2.2401.0015.50C

Atom 3959 CG2 VAL A268-53.31018.121.1031.0015.30C

Atom 3963C VAL A268-55.26219.788-2.7361.0017.15C

Atom 3964O VAL A268-54.74820.710-3.3501.0017.12O

Atom 3966N ALA A269-56.21719.014-3.2431.0017.99N

Atom 3967 CA ALA A269-56.68819.158-4.6221.0018.79C

Atom 3969 CB ALA A269-55.95818.183-5.5511.0018.26C

Atom 3973C ALA A269-58.19618.938-4.6721.0019.70C

Atom 3974O ALA A269-58.66517.834-4.9581.0019.50O

Atom 3976N PHE A270-58.94520.011-4.4171.0021.09N

Atom 3977 CA PHE A270-60.39319.910-4.2111.0022.32C

Atom 3979 CB PHE A270-60.92521.108-3.4041.0022.49C

Atom 3982 CG PHE A270-61.19322.321-4.2461.0023.31C

Atom 3983 CD1 PHE A270-62.42322.483-4.8831.0024.16C

Atom 3985 CE1 PHE A270-62.66223.569-5.6831.0023.84C

Atom 3987 CZ PHE A270-61.67524.497-5.8711.0023.93C

Atom 3989 CE2 PHE A270-60.44824.349-5.2421.0023.33C

Atom 3991 CD2 PHE A270-60.21323.268-4.4431.0023.11C

Atom 3993C PHE A270-61.17319.820-5.5151.0023.21C

Atom 3994O PHE A270-62.14219.069-5.5991.0023.48O

Atom 3996N GLU A271-60.77120.599-6.5221.0024.16N

Atom 3997 CA GLU A271-61.59520.744-7.7411.0025.01C

Atom 3999 CB GLU A271-61.06521.863-8.6551.0025.19C

Atom 4002 CG GLU A271-59.56321.909-8.7941.0027.45C

Atom 4005 CD GLU A271-58.85722.910-7.8571.0030.03C

Atom 4006 OE1 GLU A271-58.90524.145-8.1471.0029.41O

Atom 4007 OE2 GLU A271-58.22722.431-6.8651.0030.71O

Atom 4008C GLU A271-61.79919.391-8.4841.0024.95C

Atom 4009O GLU A271-60.97218.480-8.3521.0025.70O

Atom 4011N PRO A272-62.91819.242-9.2241.0024.59N

Atom 4012 CA PRO A272-63.39917.915-9.6561.0024.38C

Atom 4014 CB PRO A272-64.67518.243-10.4301.0024.25C

Atom 4017 CG PRO A272-65.10519.536-9.8691.0024.53C

Atom 4020 CD PRO A272-63.85520.295-9.6391.0024.42C

Atom 4023C PRO A272-62.47517.111-10.5491.0024.29C

Atom 4024O PRO A272-62.40615.886-10.4101.0024.45O

Atom 4025N GLN A273-61.77717.781-11.4621.0024.13N

Atom 4026 CA GLN A273-60.99817.064-12.4611.0024.13C

Atom 4028 CB GLN A273-60.52317.983-13.5671.0023.84C

Atom 4031 CG GLN A273-59.55619.041-13.1171.0024.37C

Atom 4034 CD GLN A273-60.22220.360-12.7751.0025.22C

Atom 4035 OE1 GLN A273-61.39220.412-12.3671.0025.71O

Atom 4036 NE2 GLN A273-59.46821.441-12.9321.0024.95N

Atom 4039C GLN A273-59.80816.327-11.8771.0024.33C

Atom 4040O GLN A273-59.22415.486-12.5551.0024.91O

Atom 4042N TYR A274-59.46216.607-10.6261.0024.27N

Atom 4043 CA TYR A274-58.21116.119-10.0671.0024.38C

Atom 4045 CB TYR A274-57.63917.180-9.1381.0024.36C

Atom 4048 CG TYR A274-57.06618.398-9.8191.0024.35C

Atom 4049 CD1 TYR A274-56.24918.291-10.9351.0024.13C

Atom 4051 CE1 TYR A274-55.71619.409-11.5421.0023.75C

Atom 4053 CZ TYR A274-55.96820.646-11.0191.0024.14C

Atom 4054 OH TYR A274-55.43121.762-11.5971.0024.45O

Atom 4056 CE2 TYR A274-56.75520.780-9.9031.0024.92C

Atom 4058 CD2 TYR A274-57.29719.658-9.3081.0024.74C

Atom 4060C TYR A274-58.31914.796-9.3101.0024.63C

Atom 4061O TYR A274-57.68114.613-8.2761.0024.47O

Atom 4063N SER A275-59.09713.852-9.8211.0025.00N

Atom 4064 CA SER A275-59.25412.575-9.1161.0025.11C

Atom 4066 CB SER A275-60.24411.664-9.8421.0025.14C

Atom 4069 OG SER A275-61.53712.252-9.8521.0025.96O

Atom 4071C SER A275-57.90711.885-8.9631.0024.94C

Atom 4072O SER A275-57.54411.439-7.8771.0024.57O

Atom 4074N ASP A276-57.14911.822-10.0521.0025.01N

Atom 4075 CA ASP A276-55.84011.187-9.9901.0024.92C

Atom 4077 CB ASP A276-55.10211.257-11.3241.0025.02C

Atom 4080 CG ASP A276-55.82710.495-12.4071.0026.27C

Atom 4081 OD1 ASP A276-56.3729.411-12.0801.0026.65O

Atom 4082 OD2 ASP A276-55.88010.991-13.5631.0028.21O

Atom 4083C ASP A276-55.02611.798-8.8811.0024.30C

Atom 4084O ASP A276-54.45411.064-8.0991.0024.64O

Atom 4086N CYS A277-55.00513.124-8.7721.0023.61N

Atom 4087 CA CYS A277-54.21013.746-7.7151.0022.91C

Atom 4089 CB CYS A277-54.26215.268-7.7481.0022.83C

Atom 4092 SG CYS A277-53.04815.994-6.6151.0022.43S

Atom 4094C CYS A277-54.65313.251-6.3571.0022.39C

Atom 4095O CYS A277-53.82212.833-5.5591.0022.23O

Atom 4097N ARG A278-55.96213.262-6.1151.0022.01N

Atom 4098 CA ARG A278-56.51912.813-4.8291.0021.40C

Atom 4100 CB ARG A278-58.02113.053-4.7531.0021.07C

Atom 4103 CG ARG A278-58.38214.509-4.7541.0020.39C

Atom 4106 CD ARG A278-59.85214.698-4.5271.0020.05C

Atom 4109 NE ARG A278-60.68314.331-5.6751.0018.86N

Atom 4111 CZ ARG A278-60.99315.144-6.6791.0018.58C

Atom 4112 NH1 ARG A278-60.53016.391-6.7301.0018.45N

Atom 4115 NH2 ARG A278-61.77514.702-7.6471.0019.04N

Atom 4118C ARG A278-56.22411.358-4.5301.0021.12C

Atom 4119O ARG A278-55.80411.050-3.4341.0021.59O

Atom 4121N ASN A279-56.41210.467-5.4931.0020.94N

Atom 4122 CA ASN A279-56.1689.044-5.2431.0021.08C

Atom 4124 CB ASN A279-56.6728.182-6.4011.0021.54C

Atom 4127 CG ASN A279-58.1998.346-6.6421.0023.94C

Atom 4128 OD1 ASN A279-58.9208.941-5.8231.0026.47O

Atom 4129 ND2 ASN A279-58.6857.825-7.7691.0025.52N

Atoms 4132C ASN A279-54.6998.798-4.9721.0020.30C

Atom 4133O ASN A279-54.3378.200-3.9771.0019.95O

Atom 4135N SER A280-53.8519.297-5.8561.0020.02N

Atom 4136 CA SER A280-52.4099.335-5.6121.0019.32C

Atom 4138 CB SER A280-51.72510.304-6.5801.0019.35C

Atom 4141 OG SER A280-50.6249.705-7.2121.0019.77O

Atom 4143C SER A280-52.1229.745-4.1661.0018.55C

Atom 4144O SER A280-51.5148.976-3.4361.0018.98O

Atom 4146N VAL A281-52.58010.923-3.7431.0017.45N

Atom 4147 CA VAL A281-52.23511.444-2.4161.0017.01C

Atom 4149 CB VAL A281-52.65012.934-2.2351.0017.20C

Atom 4151 CG1 VAL A281-52.49213.376-. 7871.0016.76C

Atom 4155 CG2 VAL A281-51.82613.847-3.1281.0017.13C

Atom 4159C VAL A281-52.86110.607-1.3011.0016.82C

Atom 4160O VAL A281-52.21710.314-. 2891.0016.81O

Atom 4162N ALA A282-54.11810.225-1.4811.0016.55N

Atom 4163 CA ALA A282-54.7749.304-. 5591.0016.31C

Atom 4165 CB ALA A282-56.1748.951-1.0601.0016.08C

Atom 4169C ALA A282-53.9468.036-3551.0016.31C

Atom 4170O ALA A282-53.6717.653.7621.0016.16O

Atom 4172N LYS A283-53.5397.395-1.4431.0016.92N

Atom 4173 CA LYS A283-52.7736.139-1.3681.0017.39C

Atom 4175 CB LYS A283-52.4545.596-2.7731.0017.31C

Atom 4178 CG LYS A283-53.6805.066-3.5191.0017.85C

Atom 4181 CD LYS A283-53.3894.527-4.9411.0018.98C

Atom 4184 CE LYS A283-54.7094.275-5.7181.0019.79C

Atom 4187 NZ LYS A283-54.6953.091-6.6251.0020.11N

Atom 4191C LYS A283-51.4836.338-. 5911.0017.82C

Atom 4192O LYS A283-51.1705.577.3311.0017.37O

Atom 4194N MET A284-50.7447.381-. 9641.0018.49N

Atom 4195 CA MET A284-49.4347.622-. 3731.0018.82C

Atom 4197 CB MET A284-48.6888.795-1.0471.0018.84C

Atom 4200 CG MET A284-48.1188.506-2.4441.0018.47C

Atom 4203 SD MET A284-47.5406.819-2.7181.0019.50S

Atom 4204 CE MET A284-49.0885.982-3.0941.0019.36C

Atom 4208C MET A284-49.5757.8481.1151.0018.95C

Atom 4209O MET A284-48.9017.1661.8921.0019.29O

Atom 4211N PHE A285-50.4658.7621.5071.0018.94N

Atom 4212 CA PHE A285-50.6719.0822.9301.0019.26C

Atom 4214 CB PHE A285-51.71410.1853.0731.0019.72C

Atom 4217 CG PHE A285-51.57511.0164.3281.0021.97C

Atom 4218 CD1 PHE A285-50.33511.2024.9541.0024.49C

Atom 4220 CE1 PHE A285-50.20911.9966.0861.0025.11C

Atom 4222 CZ PHE A285-51.32112.6346.5971.0026.40C

Atom 4224 CE2 PHE A285-52.56612.4705.9771.0026.44C

Atom 4226 CD2 PHE A285-52.67811.6704.8461.0024.55C

Atom 4228C PHE A285-51.0977.8793.7701.0018.74C

Atom 4229O PHE A285-50.7007.7294.9241.0018.31O

Atom 4231N SER A286-51.9037.0193.1691.0018.49N

Atom 4232 CA SER A286-52.2815.7723.7911.0018.38C

Atom 4234 CB SER A286-53.3025.0652.9261.0018.45C

Atom 4237 OG SER A286-54.3895.9492.6871.0019.82O

Atom 4239C SER A286-51.0704.8884.0481.0018.08C

Atom 4240O SER A286-50.9314.3765.1461.0018.18O

Atom 4242N PHE A287-50.1954.7143.0541.0017.72N

Atom 4243 CA PHE A287-48.9114.0243.2791.0017.23C

Atom 4245 CB PHE A287-48.1333.8011.9771.0017.09C

Atom 4248 CG PHE A287-48.5132.5551.2581.0017.26C

Atom 4249 CD1 PHE A287-48.2201.3151.8021.0018.31C

Atom 4251 CE1 PHE A287-48.583.1291.1311.0018.47C

Atom 4253 CZ PHE A287-49.237.198-. 0911.0017.88C

Atom 4255 CE2 PHE A287-49.5301.441-. 6421.0017.57C

Atom 4257 CD2 PHE A287-49.1682.608.0311.0017.79C

Atom 4259C PHE A287-48.0224.7874.2771.0016.92C

Atom 4260O PHE A287-47.3694.1735.1431.0017.18O

Atoms 4262N VAL A288-47.9896.1134.1741.0016.00N

Atom 4263 CA VAL A288-47.1486.8835.0801.0015.45C

Atom 4265 CB VAL A288-47.2898.3994.8631.0015.21C

Atom 4267 CG1 VAL A288-46.4339.1625.8521.0014.24C

Atom 4271 CG2 VAL A288-46.8988.7573.4501.0014.46C

Atoms 4275C VAL A288-47.4796.4996.5271.0015.46C

Atom 4276O VAL A288-46.5906.1607.2991.0014.79O

Atom 4278N THR A289-48.7596.4946.8801.0015.62N

Atom 4279 CA THR A289-49.1106.2728.2741.0016.09C

Atom 4281 CB THR A289-50.6026.5578.5881.0015.72C

Atom 4283 OG1 THR A289-51.4225.8277.7081.0016.52O

Atom 4285 CG2 THR A289-50.9278.0078.3711.0016.56C

Atom 4289C THR A289-48.6774.8798.7271.0016.34C

Atom 4290O THR A289-48.2344.7079.8811.0016.68O

Atom 4292N ILE A290-48.7373.9047.8201.0016.29N

Atom 4293 CA ILE A290-48.3472.5388.1661.0016.56C

Atom 4295 CB ILE A290-48.7341.5167.0961.0016.48C

Atom 4297 CG1 ILE A290-50.2471.4406.9441.0016.91C

Atom 4300 CD1 ILE A290-50.677.5645.8111.0016.52C

Atom 4304 CG2 ILE A290-48.262.1457.4881.0016.52C

Atom 4308C ILE A290-46.8422.4568.4021.0016.94C

Atom 4309O ILE A290-46.4041.9689.4431.0017.06O

Atom 4311N ILE A291-46.0482.9427.4511.0017.22N

Atom 4312 CA ILE A291-44.5952.9697.6401.0017.20C

Atom 4314 CB ILE A291-43.8423.5346.4051.0017.32C

Atom 4316 CG1 ILE A291-44.1722.7445.1251.0017.61C

Atom 4319 CD1 ILE A291-44.0041.2655.2501.0018.21C

Atom 4323 CG2 ILE A291-42.3363.5506.6371.0016.64C

Atom 4327C ILE A291-44.2623.7948.8861.0017.36C

Atom 4328O ILE A291-43.4203.4139.6701.0017.06O

Atom 4330N ASP A292-44.9504.9069.0931.0018.12N

Atom 4331 CA ASP A292-44.6275.75510.2271.0018.83C

Atom 4333 CB ASP A292-45.5117.01710.2851.0019.22C

Atom 4336 CG ASP A292-45.1857.92011.4851.0019.93C

Atom 4337 OD1 ASP A292-44.0628.46011.5441.0021.80O

Atom 4338 OD2 ASP A292-46.0488.08012.3751.0020.46O

Atom 4339C ASP A292-44.7454.94711.5091.0018.96C

Atom 4340O ASP A292-43.9025.09412.3941.0019.05O

Atom 4342N ASP A293-45.7744.09711.6101.0019.05N

Atom 4343 CA ASP A293-45.9513.27312.8171.0018.99C

Atom 4345 CB ASP A293-47.2372.44312.7901.0018.95C

Atom 4348 CG ASP A293-48.4963.27212.9211.0019.27C

Atom 4349 OD1 ASP A293-48.4834.36113.5231.0021.51O

Atom 4350 OD2 ASP A293-49.5362.81212.4211.0019.61O

Atom 4351C ASP A293-44.7832.32212.9351.0019.07C

Atom 4352O ASP A293-44.2442.13514.0241.0019.35O

Atom 4354N ILE A294-44.3901.73011.8051.0019.10N

Atom 4355 CA ILE A294-43.320.72711.7861.0019.04C

Atom 4357 CB ILE A294-43.137.10910.3861.0018.49C

Atom 4359 CG1 ILE A294-44.343-. 75410.0381.0017.60C

Atom 4362 CD1 ILE A294-44.204-1.5048.7521.0016.77C

Atom 4366 CG2 ILE A294-41.895-. 74510.3481.0018.77C

Atom 4370C ILE A294-41.9741.27312.2981.0019.55C

Atom 4371O ILE A294-41.234.55012.9741.0019.75O

Atom 4373N TYR A295-41.6492.52511.9831.0019.75N

Atom 4374 CA TYR A295-40.4113.10312.4761.0019.91C

Atom 4376 CB TYR A295-39.8564.17811.5421.0019.66C

Atom 4379 CG TYR A295-39.2063.69510.2451.0018.19C

Atom 4380 CD1 TYR A295-37.8213.72710.0751.0016.19C

Atom 4382 CE1 TYR A295-37.2223.3318.8821.0014.68C

Atom 4384 CZ TYR A295-38.0042.9067.8281.0015.04C

Atom 4385 OH TYR A295-37.4282.4856.6311.0012.25O

Atom 4387 CE2 TYR A295-39.3832.8717.9751.0016.48C

Atom 4389 CD2 TYR A295-39.9753.2719.1721.0017.01C

Atom 4391C TYR A295-40.6473.67713.8581.0020.73C

Atom 4392O TYR A295-39.7493.63514.7171.0021.64O

Atom 4394N ASP A296-41.8434.20014.1031.0021.38N

Atom 4395 CA ASP A296-42.1004.86515.3911.0022.20C

Atom 4397 CB ASP A296-43.4215.64415.3911.0022.69C

Atom 4400 CG ASP A296-43.5676.54816.6071.0023.85C

Atom 4401 OD1 ASP A296-42.5687.17917.0141.0025.49O

Atom 4402 OD2 ASP A296-44.6896.64817.1451.0026.12O

Atom 4403C ASP A296-42.1063.89016.5491.0022.10C

Atom 4404O ASP A296-41.3764.08217.5061.0022.14O

Atom 4406N VAL A297-42.9002.82816.4351.0022.25N

Atom 4407 CA VAL A297-43.1631.93717.5701.0022.22C

Atom 4409 CB VAL A297-44.6352.11618.0571.0022.07C

Atom 4411 CG1 VAL A297-44.9583.58718.2151.0021.63C

Atom 4415 CG2 VAL A297-45.6181.45917.0991.0020.76C

Atom 4419C VAL A297-42.861.42217.3731.0022.49C

Atom 4420O VAL A297-42.517-. 25518.3431.0022.40O

Atom 4422N TYR A298-42.990-. 11716.1571.0022.69N

Atom 4423 CA TYR A298-43.065-1.57915.9931.0022.90C

Atom 4425 CB TYR A298-44.089-1.97414.9341.0022.77C

Atom 4428 CG TYR A298-44.341-3.46914.9321.0023.74C

Atom 4429 CD1 TYR A298-45.249-4.04315.8191.0025.72C

Atom 4431 CE1 TYR A298-45.484-5.43515.8331.0026.12C

Atom 4433 CZ TYR A298-44.798-6.24714.9541.0025.59C

Atom 4434 OH TYR A298-45.027-7.59314.9701.0025.33O

Atom 4436 CE2 TYR A298-43.890-5.70214.0621.0024.79C

Atom 4438 CD2 TYR A298-43.661-4.31714.0611.0024.20C

Atom 4440C TYR A298-41.750-2.25815.6491.0023.02C

Atom 4441O TYR A298-41.387-3.25716.2561.0022.80O

Atom 4443N GLY A299-41.069-1.74714.6341.0023.47N

Atom 4444 CA GLY A299-39.839-2.36114.1491.0023.36C

Atom 4447C GLY A299-38.631-1.97814.9841.0023.27C

Atom 4448O GLY A299-38.532-. 85815.5011.0023.35O

Atom 4450N THR A300-37.702-2.91815.0981.0023.11N

Atom 4451 CA THR A300-36.459-2.68215.7971.0022.90C

Atom 4453 CB THR A300-35.869-3.95716.3861.0022.83C

Atom 4455 OG1 THR A300-35.328-4.75615.3281.0022.61O

Atom 4457 CG2 THR A300-36.928-4.73217.1621.0022.18C

Atom 4461C THR A300-35.482-2.12014.7961.0023.00C

Atom 4462O THR A300-35.606-2.36413.6021.0023.13O

Atom 4464N LEU A301-34.496-1.39415.3091.0023.07N

Atom 4465 CA LEU A301-33.596-. 57214.4981.0022.84C

Atom 4467 CB LEU A301-32.515.00715.4031.0022.80C

Atom 4470 CG LEU A301-31.9651.41215.1821.0022.39C

Atom 4472 CD1 LEU A301-32.9832.36514.5871.0022.44C

Atom 4476 CD2 LEU A301-31.4821.91916.5361.0022.19C

Atom 4480C LEU A301-32.964-1.35813.3611.0022.95C

Atom 4481O LEU A301-32.910-. 88812.2321.0022.50O

Atom 4483N ASP A302-32.511-2.56913.6731.0023.35N

Atom 4484 CA ASP A302-31.929-3.46912.6701.0023.65C

Atom 4486 CB ASP A302-31.332-4.74713.3281.0024.12C

Atom 4489 CG ASP A302-29.984-4.49814.0571.0025.23C

Atom 4490 OD1 ASP A302-29.003-4.05113.4091.0026.43O

Atom 4491 OD2 ASP A302-29.896-4.78015.2771.0026.92O

Atom 4492C ASP A302-32.945-3.85911.5811.0023.11C

Atom 4493O ASP A302-32.544-4.08610.4451.0023.05O

Atom 4495N GLU A303-34.235-3.96511.9271.0022.63N

Atom 4496 CA GLU A303-35.295-4.24810.9311.0022.40C

Atom 4498 CB GLU A303-36.625-4.67511.5891.0022.20C

Atom 4501 CG GLU A303-36.537-5.95612.4261.0022.66C

Atom 4504 CD GLU A303-37.832-6.34113.1591.0022.69C

Atom 4505 OE1 GLU A303-38.614-5.44913.5681.0022.23O

Atom 4506 OE2 GLU A303-38.051-7.55813.3381.0021.64O

Atoms 4507C GLU A303-35.533-3.01710.0671.0022.35C

Atom 4508O GLU A303-35.658-3.1058.8411.0022.27O

Atom 4510N LEU A304-35.597-1.86610.7241.0022.34N

Atom 4511 CA LEU A304-35.776-. 60710.0401.0022.26C

Atom 4513 CB LEU A304-35.861.53711.0521.0022.49C

Atom 4516 CG LEU A304-37.089.51711.9731.0023.05C

Atom 4518 CD1 LEU A304-37.1091.70812.9321.0023.46C

Atom 4522 CD2 LEU A304-38.353.51111.1421.0023.96C

Atom 4526C LEU A304-34.634-. 3839.0631.0022.09C

Atom 4527O LEU A304-34.873.0947.9691.0022.32O

Atom 4529N GLU A305-33.408-. 7409.4501.0021.91N

Atom 4530 CA GLU A305-32.259-. 6858.5411.0021.93C

Atom 4532 CB GLU A305-30.988-1.1949.2191.0022.35C

Atom 4535 CG GLU A305-30.363-. 25810.2491.0024.12C

Atom 4538 CD GLU A305-29.7511.0029.6491.0026.11C

Atom 4539 OE1 GLU A305-29.2751.84610.4541.0025.68O

Atom 4540 OE2 GLU A305-29.7561.1468.3911.0027.67O

Atom 4541C GLU A305-32.475-1.5247.2951.0021.54C

Atom 4542O GLU A305-32.010-1.1626.2201.0021.75O

Atom 4544N LEU A306-33.155-2.6607.4481.0021.21N

Atom 4545 CA LEU A306-33.459-3.5576.3161.0020.66C

Atom 4547 CB LEU A306-33.880-4.9566.7951.0020.26C

Atom 4550 CG LEU A306-32.725-5.8547.2201.0019.57C

Atom 4552 CD1 LEU A306-33.261-7.1507.7771.0020.18C

Atom 4556 CD2 LEU A306-31.791-6.1206.0611.0018.29C

Atom 4560C LEU A306-34.535-2.9675.4161.0020.23C

Atom 4561O LEU A306-34.412-2.9664.1971.0019.97O

Atom 4563N PHE A307-35.588-2.4576.0231.0019.99N

Atom 4564 CA PHE A307-36.635-1.8615.2371.0020.00C

Atom 4566 CB PHE A307-37.771-1.3886.1181.0020.08C

Atom 4569 CG PHE A307-39.011-1.1155.3701.0019.05C

Atom 4570 CD1 PHE A307-39.895-2.1185.1191.0018.77C

Atom 4572 CE1 PHE A307-41.037-1.8734.4211.0020.07C

Atom 4574 CZ PHE A307-41.296-. 6213.9591.0019.63C

Atom 4576 CE2 PHE A307-40.411.3914.1991.0019.27C

Atom 4578 CD2 PHE A307-39.278.1424.9001.0019.17C

Atom 4580C PHE A307-36.087-. 6954.4471.0020.25C

Atom 4581O PHE A307-36.356-. 5893.2421.0020.08O

Atom 4583N THR A308-35.325.1675.1371.0020.51N

Atom 4584 CA THR A308-34.73713794.5381.0020.60C

Atom 4586 CB THR A308-33.8602.1775.5411.0020.41C

Atom 4588 OG1 THR A308-34.6722.6616.6111.0020.05O

Atom 4590 CG2 THR A308-33.1983.3764.8641.0020.38C

Atom 4594C THR A308-33.8951.0093.3311.0020.82C

Atom 4595O THR A308-34.0571.5712.2431.0020.45O

Atom 4597N ASP A309-33.020.0313.5221.0021.32N

Atom 4598 CA ASP A309-32.138-. 3992.4491.0021.88C

Atom 4600 CB ASP A309-31.042-1.3242.9711.0022.44C

Atom 4603 CG ASP A309-30.164-1.8471.8571.0025.69C

Atom 4604 OD1 ASP A309-29.599-1.0101.0891.0028.02O

Atom 4605 OD2 ASP A309-30.076-3.1001.7301.0030.59O

Atom 4606C ASP A309-32.928-1.0851.3571.0021.17C

Atom 4607O ASP A309-32.601-. 948.1881.0020.95O

Atom 4609N ALA A310-33.965-1.8181.7571.0020.99N

Atom 4610 CA ALA A310-34.885-2.474.8281.0020.91C

Atom 4612 CB ALA A310-35.931-3.2441.5911.0020.77C

Atom 4616C ALA A310-35.567-1.501-1231.0021.08C

Atom 4617O ALA A310-35.745-1.816-1.3051.0020.76O

Atoms 4619N VAL A311-35.958-. 334.4021.0021.51N

Atom 4620 CA VAL A311-36.594.719-. 3961.0021.50C

Atom 4622 CB VAL A311-37.4241.715.4771.0021.73C

Atom 4624 CG1 VAL A311-38.7241.076.9411.0021.01C

Atom 4628 CG2 VAL A311-37.7652.993-. 2921.0021.88C

Atom 4632C VAL A311-35.5531.445-1.2301.0021.67C

Atom 4633O VAL A311-35.8111.728-2.3891.0021.71O

Atom 4635N GLU A312-34.3811.724-. 6631.0022.25N

Atom 4636 CA GLU A312-33.2482.284-1.4431.0023.00C

Atom 4638 CB GLU A312-31.9512.331-. 6081.0023.36C

Atom 4641 CG GLU A312-31.8973.383.5111.0024.72C

Atom 4644 CD GLU A312-30.5263.4691.1891.0027.09C

Atom 4645 OE1 GLU A312-30.0834.6081.4581.0030.07O

Atom 4646 OE2 GLU A312-29.8852.4181.4541.0027.86O

Atom 4647C GLU A312-32.9541.498-2.7311.0023.13C

Atom 4648O GLU A312-32.8512.064-3.8031.0022.88O

Atom 4650N ARG A313-32.819.188-2.6151.0023.74N

Atom 4651 CA ARG A313-32.400-., 628-3.7431.0024.46C

Atom 4653 CB ARG A313-31.758-1.916-3.2321.0025.01C

Atom 4656 CG ARG A313-30.421-1.667-2.4811.0027.74C

Atom 4659 CD ARG A313-29.715-2.963-2.0721.0031.41C

Atom 4662 NE ARG A313-30.675-3.921-1.4991.0034.94N

Atom 4664 CZ ARG A313-31.203-4.974-2.1381.0037.87C

Atom 4665 NH1 ARG A313-30.861-5.282-3.4021.0038.35N

Atom 4668 NH2 ARG A313-32.079-5.746-1.4951.0038.82N

Atom 4671C ARG A313-33.523-., 914-4.7391.0024.27C

Atom 4672O ARG A313-33.257-1.178-5.8981.0024.17O

Atom 4674N TRP A314-34.770-, 873-4.2821.0024.59N

Atom 4675 CA TRP A314-35.939-1.042-5.1421.0024.66C

Atom 4677 CB TRP A314-36.175.234-5.9611.0024.39C

Atom 4680 CG TRP A314-37.575.382-6.3861.0022.61C

Atom 4681 CD1 TRP A314-38.073.204-7.6351.0021.66C

Atom 4683 NE1 TRP A314-39.429.403-7.6341.0021.42N

Atom 4685 CE2 TRP A314-39.829.707-6.3601.0020.99C

Atom 4686 CD2 TRP A314-38.683.701-5.5501.0021.41C

Atom 4687 CE3 TRP A314-38.817.991-4.1911.0021.48C

Atom 4689 CZ3 TRP A314-40.0801.277-3.6931.0021.38C

Atom 4691 CH2 TRP A314-41.2041.269-4.5231.0020.84C

Atom 4693 CZ2 TRP A314-41.099.985-5.8571.0020.87C

Atom 4695C TRP A314-35.831-2.286-6.0381.0025.65C

Atom 4696O TRP A314-36.069-2.238-7.2591.0025.69O

Atoms 4698N ASP A315-35.480-3.400-5.4041.0026.79N

Atom 4699 CA ASP A315-35.253-4.667-6.0871.0028.01C

Atom 4701 CB ASP A315-33.801-5.097-5.8901.0028.07C

Atom 4704 CG ASP A315-33.553-6.536-6.2961.0029.92C

Atom 4705 OD1 ASP A315-34.262-7.026-7.1971.0032.58O

Atom 4706 OD2 ASP A315-32.648-7.194-5.7221.0032.73O

Atom 4707C ASP A315-36.202-5.710-5.5181.0028.91C

Atom 4708O ASP A315-36.019-6.163-4.3991.0029.17O

Atom 4710N VAL A316-37.218-6.091-6.2831.0030.25N

Atom 4711 CA VAL A316-38.233-7.012-5.7781.0031.47C

Atom 4713 CB VAL A316-39.396-7.156-6.7551.0031.56C

Atom 4715 CG1 VAL A316-40.668-7.590-6.0271.0030.99C

Atom 4719 CG2 VAL A316-39.033-8.141-7.8621.0031.84C

Atom 4723C VAL A316-37.663-8.405-5.5401.0032.86C

Atom 4724O VAL A316-38.170-9.153-4.7081.0032.99O

Atom 4726N ASN A317-36.607-8.750-6.2781.0034.55N

Atom 4727 CA ASN A317-35.940-10.060-6.1601.0035.53C

Atom 4729 CB ASN A317-35.013-10.298-7.3671.0035.68C

Atom 4732 CG ASN A317-35.752-10.264-8.7131.0035.92C

Atom 4733 OD1 ASN A317-36.634-11.092-8.9711.0036.95O

Atom 4734 ND2 ASN A317-35.368-9.323-9.5851.0034.17N

Atom 4737C ASN A317-35.126-10.225-4.8711.0036.40C

Atom 4738O ASN A317-34.385-11.195-4.7471.0036.47O

Atom 4740N ALA A318-35.239-9.265-3.9441.0037.52N

Atom 4741 CA ALA A318-34.614-9.335-2.6131.0038.45C

Atom 4743 CB ALA A318-33.371-8.465-2.5571.0038.43C

Atom 4747C ALA A318-35.631-8.902-1.5541.0039.28C

Atom 4748O ALA A318-35.361-8.094-. 6621.0039.55O

Atom 4750N ILE A319-36.823-9.456-1.6981.0040.17N

Atom 4751 CA ILE A319-37.905-9.310-. 7401.0040.49C

Atom 4753 CB ILE A319-39.275-9.588-1.4691.0040.64C

Atom 4755 CG1 ILE A319-40.473-9.078-., 6831.0040.88C

Atom 4758 CD1 ILE A319-41.799-9.535-1.2801.0040.86C

Atom 4762 CG2 ILE A319-39.460-11.082-1.8011.0040.50C

Atom 4766C ILE A319-37.656-10.319.3931.0040.69C

Atom 4767O ILE A319-38.136-10.1381.5041.0040.88O

Atom 4769N ASN A320-36.886-11.374.1041.0040.79N

Atom 4770 CA ASN A320-36.689-12.4831.0491.0040.64C

Atom 4772 CB ASN A320-36.240-13.761.3141.0040.73C

Atom 4775 CG ASN A320-37.370-14.422-. 4681.0040.98C

Atom 4776 OD1 ASN A320-38.556-14.309-., 1191.0040.77O

Atom 4777 ND2 ASN A320-37.001-15.131-1.5291.0041.31N

Atom 4780C ASN A320-35.711-12.1752.1691.0040.16C

Atom 4781O ASN A320-35.546-12.9783.0771.0040.15O

Atom 4783N ASP A321-35.067-11.0172.1011.0039.66N

Atom 4784 CA ASP A321-34.111-10.6153.1261.0039.51C

Atom 4786 CB ASP A321-33.114-9.5712.5751.0040.17C

Atom 4789 CG ASP A321-32.595-9.9041.1521.0042.12C

Atom 4790 OD1 ASP A321-32.425-11.115.8201.0044.15O

Atom 4791 OD2 ASP A321-32.354-8.934.3751.0043.28O

Atom 4792C ASP A321-34.851-10.0304.3371.0038.27C

Atom 4793O ASP A321-34.304-9.9875.4431.0038.15O

Atom 4795N LEU A322-36.089-9.5834.1081.0036.72N

Atom 4796 CA LEU A322-36.887-8.8755.1041.0035.38C

Atom 4798 CB LEU A322-37.894-7.9424.4221.0035.15C

Atom 4801 CG LEU A322-37.370-6.8403.5031.0034.83C

Atom 4803 CD1 LEU A322-38.479-6.2862.6261.0034.45C

Atom 4807 CD2 LEU A322-36.742-5.7404.3161.0034.89C

Atom 4811C LEU A322-37.683-9.8345.9631.0034.57C

Atom 4812O LEU A322-37.975-10.9335.5271.0034.27O

Atom 4814N PRO A323-38.039-9.4027.1891.0033.93N

Atom 4815 CA PRO A323-39.070-9.9178.0671.0033.49C

Atom 4817 CB PRO A323-39.151-8.8409.1411.0033.31C

Atom 4820 CG PRO A323-37.791-8.4199.3111.0033.67C

Atom 4823 CD PRO A323-37.154-8.4967.9411.0034.20C

Atom 4826C PRO A323-40.429-10.0367.4251.0033.33C

Atom 4827O PRO A323-40.776-9.2326.5791.0033.35O

Atom 4828N ASP A324-41.209-11.0057.8911.0033.37N

Atom 4829 CA ASP A324-42.511-11.3297.3131.0033.36C

Atom 4831 CB ASP A324-43.137-12.5428.0371.0033.59C

Atom 4834 CG ASP A324-42.496-13.8817.6191.0034.18C

Atom 4835 OD1 ASP A324-41.885-13.9156.5181.0036.44O

Atom 4836 OD2 ASP A324-42.607-14.8878.3711.0032.19O

Atom 4837C ASP A324-43.484-10.1497.2891.0032.90C

Atom 4838O ASP A324-44.108-9.8856.2551.0033.36O

Atom 4840N TYR A325-43.606-9.4238.3921.0032.10N

Atom 4841 CA TYR A325-44.515-8.2798.4001.0031.65C

Atom 4843 CB TYR A325-44.718-7.7269.8151.0031.68C

Atom 4846 CG TYR A325-43.618-6.84610.3521.0031.35C

Atom 4847 CD1 TYR A325-42.507-7.38910.9921.0031.31C

Atom 4849 CE1 TYR A325-41.497-6.57411.5041.0031.46C

Atom 4851 CZ TYR A325-41.613-5.19211.3921.0032.41C

Atom 4852 OH TYR A325-40.637-4.33611.8931.0032.78O

Atom 4854 CE2 TYR A325-42.723-4.64410.7691.0032.17C

Atom 4856 CD2 TYR A325-43.713-5.47010.2611.0031.47C

Atom 4858C TYR A325-44.094-7.1797.4241.0031.17C

Atom 4859O TYR A325-44.947-6.4586.9201.0031.09O

Atom 4861N MET A326-42.796-7.0687.1451.0030.73N

Atom 4862 CA MET A326-42.277-6.0366.2251.0030.49C

Atom 4864 CB MET A326-40.832-5.7026.5651.0030.16C

Atom 4867 CG MET A326-40.725-4.9187.8301.0029.57C

Atom 4870 SD MET A326-39.057-4.3768.1661.0028.39S

Atom 4871 CE MET A326-39.407-2.7878.9331.0026.18C

Atom 4875C MET A326-42.371-6.4184.7481.0030.59C

Atom 4876O MET A326-42.786-5.6033.9201.0030.48O

Atoms 4878N LYS A327-41.936-7.6434.4381.0030.68N

Atoms 4879 CA LYS A327-42.170-8.2993.1431.0030.56C

Atom 4881 CB LYS A327-42.267-9.8303.3261.0030.84C

Atom 4884 CG LYS A327-41.052-10.6072.8441.0032.35C

Atom 4887 CD LYS A327-40.990-12.0193.4121.0034.43C

Atom 4890 CE LYS A327-40.221-12.9412.4621.0035.77C

Atom 4893 NZ LYS A327-39.691-14.1623.1501.0037.20N

Atom 4897C LYS A327-43.453-7.8112.5151.0029.89C

Atom 4898O LYS A327-43.447-7.2201.4361.0029.85O

Atoms 4900N LEU A328-44.544-8.0463.2301.0029.10N

Atom 4901 CA LEU A328-45.871-7.7812.7301.0028.77C

Atom 4903 CB LEU A328-46.899-8.3363.7091.0028.81C

Atom 4906 CG LEU A328-48.349-8.3643.2571.0028.82C

Atom 4908 CD1 LEU A328-48.519-9.2602.0461.0029.09C

Atom 4912 CD2 LEU A328-49.202-8.8454.4111.0029.16C

Atoms 4916C LEU A328-46.057-6.2912.5641.0028.61C

Atom 4917O LEU A328-46.582-5.8281.5541.0029.00O

Atom 4919N CYS A329-45.612-5.5323.5571.0028.24N

Atom 4920 CA CYS A329-45.737-4.0863.5041.0027.95C

Atom 4922 CB CYS A329-45.311-3.4594.8341.0028.21C

Atom 4925 SG CYS A329-45.280-1.6304.8171.0032.39S

Atom 4927C CYS A329-44.921-3.5412.3271.0026.34C

Atom 4928O CYS A329-45.459-2.8531.4751.0026.23O

Atom 4930N PHE A330-43.642-3.8822.2691.0024.82N

Atom 4931 CA PHE A330-42.790-3.5141.1301.0023.82C

Atom 4933 CB PHE A330-41.397-4.1371.2831.0023.64C

Atom 4936 CG PHE A330-40.492-3.873.1171.0022.63C

Atom 4937 CD1 PHE A330-39.845-2.658-., 0081.0021.68C

Atom 4939 CE1 PHE A330-39.020-2.393-1.0821.0021.07C

Atom 4941 CZ PHE A330-38.829-3.343-2.0461.0022.00C

Atom 4943 CE2 PHE A330-39.474-4.568-1.9441.0022.60C

Atom 4945 CD2 PHE A330-40.309-4.824-., 8651.0022.36C

Atom 4947C PHE A330-43.348-3.863-. 2811.0022.99C

Atom 4948O PHE A330-43.350-3.012-1.1821.0022.98O

Atom 4950N LEU A331-43.789-5.101-. 4921.0021.65N

Atom 4951 CA LEU A331-44.306-5.484-1.8161.0020.74C

Atom 4953 CB LEU A331-44.573-6.990-1.9121.0020.57C

Atom 4956 CG LEU A331-44.959-7.575-3.2771.0019.82C

Atom 4958 CD1 LEU A331-43.936-7.246-4.3291.0019.00C

Atom 4962 CD2 LEU A331-45.128-9.092-3.1651.0019.11C

Atom 4966C LEU A331-45.568-4.710-2.1591.0019.98C

Atom 4967O LEU A331-45.753-4.324-3.3001.0020.15O

Atom 4969N ALA A332-46.431-4.495-1.1721.0019.09N

Atom 4970 CA ALA A332-47.619-3.675-1.3531.0018.46C

Atom 4972 CB ALA A332-48.406-3.587-. 0451.0018.20C

Atom 4976C ALA A332-47.248-2.279-1.8561.0017.91C

Atom 4977O ALA A332-47.890-1.745-2.7441.0017.98O

Atom 4979N LEU A333-46.197-1.706-1.2951.0017.62N

Atom 4980 CA LEU A333-45.753-., 353-1.6371.0017.60C

Atom 4982 CB LEU A333-44.725.132-. 5981.0017.59C

Atom 4985 CG LEU A333-44.1221.533-. 7611.0017.16C

Atom 4987 CD1 LEU A333-45.1662.629-. 5541.0016.99C

Atom 4991 CD2 LEU A333-42.9791.704.2001.0015.89C

Atoms 4995C LEU A333-45.100-., 320-3.0051.0017.70C

Atom 4996O LEU A333-45.321.603-3.7951.0017.86O

Atom 4998N TYR A334-44.248-1.319-3.2341.0017.63N

Atom 4999 CA TYR A334-43.542-1.531-4.4891.0017.44C

Atom 5001 CB TYR A334-42.893-2.908-4.4441.0017.50C

Atom 5004 CG TYR A334-41.897-3.169-5.5231.0018.03C

Atom 5005 CD1 TYR A334-40.698-2.473-5.5691.0018.83C

Atom 5007 CE1 TYR A334-39.764-2.725-6.5421.0018.13C

Atom 5009 CZ TYR A334-40.016-3.678-7.4781.0018.78C

Atom 5010 OH TYR A334-39.096-3.929-8.4391.0021.71O

Atom 5012 CE2 TYR A334-41.180-4.391-7.4621.0019.74C

Atom 5014 CD2 TYR A334-42.118-4.139-6.4721.0019.59C

Atom 5016C TYR A334-44.500-1.497-5.6491.0017.43C

Atom 5017O TYR A334-44.264-,. 803-6.6361.0017.64O

Atom 5019N ASN A335-45.589-2.253-5.5041.0017.30N

Atom 5020 CA ASN A335-46.574-2.448-6.5531.0017.23C

Atom 5022 CB ASN A335-47.544-3.551-6.1661.0017.32C

Atom 5025 CG ASN A335-46.952-4.920-6.3321.0018.16C

Atom 5026 OD1 ASN A335-45.913-5.090-6.9891.0018.99O

Atom 5027 ND2 ASN A335-47.616-5.921-5.7491.0018.49N

Atom 5030C ASN A335-47.365-1.218-6.8121.0017.12C

Atom 5031O ASN A335-47.613-. 852-7.9651.0017.36O

Atom 5033N THR A336-47.789-., 602-5.7221.0017.20N

Atom 5034 CA THR A336-48.601.593-5.7791.0017.36C

Atom 5036 CB THR A336-48.8881.104-4.3811.0017.20C

Atom 5038 OG1 THR A336-49.611.103-3.6571.0016.26O

Atom 5040 CG2 THR A336-49.6882.384-4.4521.0017.18C

Atom 5044C THR A336-47.8931.691-6.5501.0017.84C

Atom 5045O THR A336-48.5112.388-7.3601.0018.07O

Atom 5047N ILE A337-46.5951.831-6.2981.0018.14N

Atom 5048 CA ILE A337-45.8172.904-6.8951.0018.50C

Atom 5050 CB ILE A337-44.5843.209-6.0661.0018.31C

Atom 5052 CG1 ILE A337-45.0143.997-4.8371.0018.58C

Atom 5055 CD1 ILE A337-44.0433.866-3.7351.0020.66C

Atom 5059 CG2 ILE A337-43.5703.988-6.8671.0016.98C

Atom 5063C ILE A337-45.4472.548-8.3141.0019.29C

Atom 5064O ILE A337-45.5563.387-9.2141.0019.17O

Atom 5066N ASN A338-45.0331.299-8.5131.0020.16N

Atom 5067 CA ASN A338-44.861.767-9.8641.0020.93C

Atom 5069 CB ASN A338-44.409-., 695-9.8301.0021.07C

Atom 5072 CG ASN A338-42.953-., 845-9.4391.0021.61C

Atom 5073 OD1 ASN A338-42.232.143-9.3081.0022.40O

Atom 5074 ND2 ASN A338-42.509-2.086-9.2601.0021.92N

Atoms 5077C ASN A338-46.123.914-10.7191.0021.44C

Atom 5078O ASN A338-46.0221.202-11.9041.0021.25O

Atom 5080N GLU A339-47.303.747-10.1281.0022.21N

Atom 5081 CA GLU A339-48.5321.000-10.8801.0023.31C

Atom 5083 CB GLU A339-49.768.464-10.1641.0024.13C

Atom 5086 CG GLU A339-50.146-,. 936-10.6601.0028.69C

Atom 5089 CD GLU A339-50.939-1.740-9.6381.0035.06C

Atom 5090 OE1 GLU A339-51.899-1.136-9.0671.0039.51O

Atom 5091 OE2 GLU A339-50.596-2.952-9.4141.0036.64O

Atom 5092C GLU A339-48.7252.463-11.2691.0022.71C

Atom 5093O GLU A339-49.2152.743-12.3721.0022.48O

Atom 5095N ILE A340-48.3393.390-10.3901.0022.19N

Atom 5096 CA ILE A340-48.4064.813-10.7341.0021.64C

Atom 5098 CB ILE A340-48.1355.739-9.5381.0021.33C

Atomic 5100 CG1 ILE A340-49.2295.596-8.4821.0021.29C

Atomic 5103 CD1 ILE A340-48.9256.306-7.1501.0020.00C

Atom 5107 CG2 ILE A340-48.0917.177-9.9821.0020.28C

Atom 5111C ILE A340-47.4145.128-11.8611.0021.78C

Atom 5112O ILE A340-47.7865.826-12.8181.0022.13O

Atom 5114N ALA A341-46.1794.609-11.7711.0021.34N

Atom 5115 CA ALA A341-45.1474.892-12.7871.0021.03C

Atom 5117 CB ALA A341-43.8374.268-12.4061.0020.55C

Atom 5121C ALA A341-45.5924.426-14.1831.0021.32C

Atom 5122O ALA A341-45.2285.036-15.2171.0021.11O

Atom 5124N TYR A342-46.3933.355-14.1961.0021.45N

Atom 5125 CA TYR A342-47.0082.861-15.4141.0021.41C

Atom 5127 CB TYR A342-47.6271.468-15.2081.0021.31C

Atom 5130 CG TYR A342-48.336.957-16.4501.0019.60C

Atom 5131 CD1 TYR A342-47.613.463-17.5211.0016.69C

Atom 5133 CE1 TYR A342-48.231.032-18.6431.0015.50C

Atom 5135 CZ TYR A342-49.595.085-18.7281.0015.88C

Atom 5136 OH TYR A342-50.196-,. 352-19.8771.0016.46O

Atom 5138 CE2 TYR A342-50.352.558-17.6811.0016.50C

Atom 5140 CD2 TYR A342-49.725.997-16.5561.0018.17C

Atom 5142C TYR A342-48.0643.830-15.8991.0022.08C

Atom 5143O TYR A342-48.0944.169-17.0481.0022.07O

Atom 5145N ASP A343-48.9424.283-15.0321.0023.41N

Atom 5146 CA ASP A343-49.9705.211-15.4811.0024.66C

Atom 5148 CB ASP A343-50.8515.674-14.3181.0025.10C

Atom 5151 CG ASP A343-51.7204.552-13.7321.0026.06C

Atom 5152 OD1 ASP A343-52.1073.613-14.4771.0026.39O

Atom 5153 OD2 ASP A343-52.0324.642-12.5161.0027.29O

Atom 5154C ASP A343-49.3166.420-16.1421.0025.22C

Atom 5155O ASP A343-49.7556.874-17.1921.0025.47O

Atom 5157N ASN A344-48.2606.936-15.5281.0025.87N

Atom 5158 CA ASN A344-47.5088.042-16.1271.0026.41C

Atom 5160 CB ASN A344-46.4988.605-15.1341.0026.56C

Atom 5163 CG ASN A344-47.1529.407-14.0731.0026.95C

Atom 5164 OD1 ASN A344-47.49510.568-14.2961.0029.13O

Atom 5165 ND2 ASN A344-47.3678.799-12.9161.0026.36N

Atom 5168C ASN A344-46.7857.674-17.4161.0026.53C

Atom 5169O ASN A344-46.6588.508-18.3041.0026.74O

Atom 5171N LEU A345-46.2806.448-17.5101.0026.56N

Atom 5172 CA LEU A345-45.6346.019-18.7391.0026.37C

Atom 5174 CB LEU A345-44.8904.693-18.5501.0026.32C

Atom 5177 CG LEU A345-43.9954.339-19.7501.0025.96C

Atom 5179 CD1 LEU A345-42.7065.133-19.6651.0025.07C

Atom 5183 CD2 LEU A345-43.7242.835-19.8741.0024.75C

Atom 5187C LEU A345-46.6795.908-19.8561.0026.38C

Atom 5188O LEU A345-46.4356.335-20.9661.0026.52O

Atom 5190N LYS A346-47.8395.340-19.5631.0026.59N

Atom 5191 CA LYS A346-48.8805.176-20.5721.0026.89C

Atom 5193 CB LYS A346-50.0654.367-20.0111.0026.80C

Atom 5196 CG LYS A346-51.0733.931-21.0621.0026.26C

Atom 5199 CD LYS A346-52.2103.080-20.5171.0026.15C

Atom 5202 CE LYS A346-53.2273.849-19.6891.0026.40C

Atom 5205 NZ LYS A346-53.1363.506-18.2231.0027.67N

Atom 5209C LYS A346-49.3726.537-21.0711.0027.52C

Atom 5210O LYS A346-49.5626.742-22.2721.0027.57O

Atom 5212N ASP A347-49.5677.472-20.1481.0028.10N

Atom 5213 CA ASP A347-50.3098.689-20.4651.0028.58C

Atom 5215 CB ASP A347-51.3059.017-19.3291.0028.85C

Atom 5218 CG ASP A347-52.4267.950-19.1971.0030.01C

Atom 5219 OD1 ASP A347-52.8277.349-20.2231.0030.51O

Atom 5220 OD2 ASP A347-52.9107.704-18.0691.0032.61O

Atom 5221C ASP A347-49.4079.871-20.8041.0028.22C

Atom 5222O ASP A347-49.77810.710-21.6111.0028.39O

Atom 5224N LYS A348-48.2289.930-20.2061.0028.03N

Atom 5225 CA LYS A348-47.30111.021-20.4671.0028.01C

Atom 5227 CB LYS A348-46.78511.648-19.1641.0028.39C

Atom 5230 CG LYS A348-47.83412.305-18.2571.0030.18C

Atom 5233 CD LYS A348-47.14312.898-17.0031.0032.40C

Atom 5236 CE LYS A348-48.12413.121-15.8741.0033.59C

Atom 5239 NZ LYS A348-49.31913.878-16.3411.0035.48N

Atom 5243C LYS A348-46.10710.551-21.2601.0027.25C

Atom 5244O LYS A348-45.24111.345-21.5661.0027.60O

Atom 5246N GLY A349-46.0369.271-21.5831.0026.47N

Atom 5247 CA GLY A349-44.8638.742-22.2611.0026.01C

Atom 5250C GLY A349-43.5599.109-21.5871.0025.67C

Atom 5251O GLY A349-42.6139.472-22.2501.0025.85O

Atom 5253N GLU A350-43.4989.032-20.2691.0025.55N

Atom 5254 CA GLU A350-42.2729.374-19.5551.0025.76C

Atom 5256 CB GLU A350-42.33210.814-19.0211.0026.34C

Atom 5259 CG GLU A350-42.17911.928-20.1061.0029.04C

Atom 5262 CD GLU A350-40.74512.101-20.5981.0032.08C

Atom 5263 OE1 GLU A350-39.85312.170-19.7161.0035.46O

Atom 5264 OE2 GLU A350-40.51612.174-21.8391.0031.64O

Atom 5265C GLU A350-42.0848.414-18.4001.0024.87C

Atom 5266O GLU A350-43.0678.046-17.7601.0025.16O

Atom 5268N ASN A351-40.8338.009-18.1451.0023.71N

Atom 5269 CA ASN A351-40.4947.189-16.9801.0022.88C

Atom 5271 CB ASN A351-39.3516.229-17.2871.0022.88C

Atom 5274 CG ASN A351-39.1415.215-16.1841.0022.98C

Atom 5275 OD1 ASN A351-39.0065.584-15.0351.0022.68O

Atom 5276 ND2 ASN A351-39.1393.924-16.5291.0024.38N

Atom 5279C ASN A351-40.1268.058-15.7861.0022.40C

Atom 5280O ASN A351-39.0978.741-15.7851.0022.66O

Atom 5282N ILE A352-40.9658.021-14.7601.0021.55N

Atom 5283 CA ILE A352-40.7708.860-13.5911.0020.75C

Atom 5285 CB ILE A352-42.0029.788-13.3601.0020.95C

Atom 5287 CG1 ILE A352-43.2638.970-13.0221.0020.82C

Atom 5290 CD1 ILE A352-44.2379.698-12.1221.0020.21C

Atom 5294 CG2 ILE A352-42.26610.669-14.5821.0019.85C

Atom 5298C ILE A352-40.5168.016-12.3391.0020.37C

Atom 5299O ILE A352-40.5748.513-11.2241.0020.55O

Atom 5301N LEU A353-40.2366.733-12.5191.0019.98N

Atom 5302 CA LEU A353-40.0615.828-11.3871.0019.42C

Atom 5304 CB LEU A353-39.8944.392-11.8701.0019.27C

Atom 5307 CG LEU A353-39.9893.318-10.7991.0019.01C

Atom 5309 CD1 LEU A353-41.1643.574-9.8671.0018.35C

Atom 5313 CD2 LEU A353-40.0851.938-11.4681.0018.74C

Atom 5317C LEU A353-38.8906.240-10.5231.0019.11C

Atom 5318O LEU A353-39.0226.319-9.3141.0018.96O

Atom 5320N PRO A354-37.7466.549-11.1421.0019.06N

Atom 5321 CA PRO A354-36.6317.069-10.3671.0019.29C

Atom 5323 CB PRO A354-35.7497.717-11.4381.0019.25C

Atom 5326 CG PRO A354-35.9976.942-12.6381.0019.08C

Atom 5329 CD PRO A354-37.4096.472-12.5721.0019.00C

Atom 5332C PRO A354-37.0248.122-9.3281.0019.33C

Atom 5333O PRO A354-36.5348.057-8.1931.0019.73O

Atom 5334N TYR A355-37.8919.063-9.7211.0018.83N

Atom 5335 CA TYR A355-38.20610.221-8.8981.0018.79C

Atom 5337 CB TYR A355-38.83611.359-9.7071.0019.10C

Atom 5340 CG TYR A355-38.14211.708-11.0091.0020.15C

Atom 5341 CD1 TYR A355-36.94012.403-11.0271.0020.78C

Atom 5343 CE1 TYR A355-36.32112.719-12.2321.0022.19C

Atom 5345 CZ TYR A355-36.91812.347-13.4381.0022.19C

Atom 5346 OH TYR A355-36.34112.660-14.6571.0023.29O

Atom 5348 CE2 TYR A355-38.11311.677-13.4301.0021.62C

Atom 5350 CD2 TYR A355-38.72011.371-12.2271.0021.05C

Atom 5352C TYR A355-39.1559.864-7.7771.0018.43C

Atom 5353O TYR A355-39.08110.460-6.7091.0018.61O

Atom 5355N LEU A356-40.0588.917-8.0231.0017.92N

Atom 5356 CA LEU A356-40.9938.467-6.9941.0017.38C

Atom 5358 CB LEU A356-42.1367.658-7.5971.0017.17C

Atom 5361 CG LEU A356-42.9568.366-8.6821.0017.56C

Atom 5363 CD1 LEU A356-43.9337.419-9.3711.0017.47C

Atom 5367 CD2 LEU A356-43.6989.548-8.1121.0018.08C

Atom 5371C LEU A356-40.2417.623-5.9781.0017.10C

Atom 5372O LEU A356-40.3327.859-4.7831.0017.62O

Atom 5374N THR A357-39.4646.656-6.4421.0016.64N

Atom 5375 CA THR A357-38.7755.769-5.5131.0016.18C

Atom 5377 CB THR A357-38.1044.554-6.2131.0016.04C

Atom 5379 OG1 THR A357-37.0924.996-7.1231.0015.93O

Atom 5381 CG2 THR A357-39.1423.732-6.9621.0014.99C

Atom 5385C THR A357-37.7646.544-4.6861.0016.16C

Atom 5386O THR A357-37.5996.278-3.5061.0016.07O

Atom 5388N LYS A358-37.1077.524-5.2911.0016.20N

Atom 5389 CA LYS A358-36.1868.365-4.5431.0016.46C

Atom 5391 CB LYS A358-35.5189.386-5.4531.0016.80C

Atom 5394 CG LYS A358-34.61210.388-4.7411.0018.30C

Atom 5397 CD LYS A358-33.3529.738-4.1681.0020.21C

Atom 5400 CE LYS A358-32.33510.811-3.7681.0021.96C

Atom 5403 NZ LYS A358-31.16310.275-3.0191.0022.95N

Atom 5407C LYS A358-36.9369.083-3.4401.0016.26C

Atom 5408O LYS A358-36.4489.161-2.3201.0016.15O

Atom 5410N ALA A359-38.1269.593-3.7631.0016.11N

Atom 5411 CA ALA A359-38.93710.332-2.7981.0016.10C

Atom 5413 CB ALA A359-40.22110.768-3.4061.0015.71C

Atom 5417C ALA A359-39.2159.476-1.5881.0016.52C

Atom 5418O ALA A359-39.2479.970-. 4421.0016.82O

Atom 5420N TRP A360-39.3988.187-1.8431.0016.79N

Atom 5421 CA TRP A360-39.7047.247-. 7801.0017.25C

Atom 5423 CB TRP A360-40.3906.006-1.3521.0017.41C

Atom 5426 CG TRP A360-41.8526.129-1.3181.0017.06C

Atom 5427 CD1 TRP A360-42.6646.451-2.3461.0017.94C

Atom 5429 NE1 TRP A360-43.9676.489-1.9261.0018.03N

Atom 5431 CE2 TRP A360-44.0026.193-. 5921.0017.72C

Atom 5432 CD2 TRP A360-42.6845.965-. 1791.0016.60C

Atom 5433 CE3 TRP A360-42.4415.6541.1551.0016.65C

Atom 5435 CZ3 TRP A360-43.5085.5732.0221.0016.91C

Atom 5437 CH2 TRP A360-44.8115.8071.5861.0017.82C

Atom 5439 CZ2 TRP A360-45.0806.114.2821.0018.49C

Atom 5441C TRP A360-38.4906.865.0731.0017.52C

Atom 5442O TRP A360-38.6036.7671.2971.0017.38O

Atom 5444N ALA A361-37.3446.651-5681.0017.82N

Atom 5445 CA ALA A361-36.1226.336.1571.0018.11C

Atom 5447 CB ALA A361-34.9826.050-8051.0017.92C

Atom 5451C ALA A361-35.7817.5071.0631.0018.52C

Atom 5452O ALA A361-35.4347.3272.2291.0018.48O

Atom 5454N ASP A362-35.9118.711.5211.0019.16N

Atom 5455 CA ASP A362-35.6279.9251.2761.0019.90C

Atom 5457 CB ASP A362-35.79711.167.3871.0020.39C

Atom 5460 CG ASP A362-34.59611.424-. 5301.0021.84C

Atom 5461 OD1 ASP A362-33.63010.625-. 5611.0022.88O

Atom 5462 OD2 ASP A362-34.63012.453-1.2311.0024.83O

Atom 5463C ASP A362-36.53210.0392.5101.0019.91C

Atom 5464O ASP A362-36.07410.4273.5911.0019.76O

Atom 5466N LEU A363-37.8139.7072.3461.0019.95N

Atom 5467 CA LEU A363-38.7479.6883.4781.0019.85C

Atom 5469 CB LEU A363-40.1759.4153.0061.0019.70C

Atom 5472 CG LEU A363-41.2199.2934.1231.0018.58C

Atom 5474 CD1 LEU A363-41.18910.5514.9651.0018.37C

Atom 5478 CD2 LEU A363-42.5979.0733.5511.0016.43C

Atom 5482C LEU A363-38.3688.6134.4881.0020.24C

Atom 5483O LEU A363-38.3148.8755.6911.0020.52O

Atom 5485N CYS A364-38.1297.3973.9971.0020.29N

Atom 5486 CA CYS A364-37.7416.3084.8741.0020.39C

Atom 5488 CB CYS A364-37.5954.9854.1111.0020.37C

Atom 5491 SG CYS A364-39.2084.2013.6661.0020.69S

Atom 5493C CYS A364-36.4676.6835.6461.0020.59C

Atom 5494O CYS A364-36.3866.4456.8631.0020.82O

Atom 5496N ASN A365-35.4957.3144.9801.0020.35N

Atom 5497 CA ASN A365-34.2827.7165.6971.0020.14C

Atom 5499 CB ASN A365-33.1888.2034.7541.0020.18C

Atom 5502 CG ASN A365-32.3597.0644.1841.0020.55C

Atom 5503 OD1 ASN A365-31.7066.3164.9251.0020.40O

Atom 5504 ND2 ASN A365-32.3656.9382.8541.0021.25N

Atom 5507C ASN A365-34.5908.7466.7791.0019.92C

Atom 5508O ASN A365-33.9978.6857.8571.0019.94O

Atom 5510N ALA A366-35.5319.6586.5071.0019.58N

Atom 5511 CA ALA A366-36.03610.5787.5371.0019.39C

Atom 5513 CB ALA A366-37.08311.5076.9711.0018.79C

Atom 5517C ALA A366-36.5979.7848.7301.0019.75C

Atom 5518O ALA A366-36.21510.0499.8911.0019.53O

Atom 5520N PHE A367-37.4608.7978.4471.0019.69N

Atom 5521 CA PHE A367-37.9857.9259.5021.0020.11C

Atom 5523 CB PHE A367-38.9526.8578.9671.0020.47C

Atom 5526 CG PHE A367-40.2937.3708.4941.0021.35C

Atom 5527 CD1 PHE A367-40.9858.3479.1801.0021.54C

Atom 5529 CE1 PHE A367-42.2248.7758.7321.0021.47C

Atom 5531 CZ PHE A367-42.7988.2137.6121.0021.87C

Atom 5533 CE2 PHE A367-42.1357.2306.9241.0022.60C

Atom 5535 CD2 PHE A367-40.8946.7987.3731.0022.90C

Atom 5537C PHE A367-36.8717.17910.2521.0020.12C

Atom 5538O PHE A367-36.9407.00911.4761.0019.88O

Atom 5540N LEU A368-35.8686.6969.5161.0020.30N

Atom 5541 CA LEU A368-34.7755.93110.1331.0020.19C

Atom 5543 CB LEU A368-33.7835.4139.0851.0020.08C

Atom 5546 CG LEU A368-32.7434.3639.5141.0019.30C

Atom 5548 CD1 LEU A368-33.3843.22710.2601.0018.66C

Atom 5552 CD2 LEU A368-31.9683.8078.3191.0018.16C

Atom 5556C LEU A368-34.0636.81211.1281.0020.41C

Atom 5557O LEU A368-33.8426.40712.2571.0020.01O

Atom 5559N GLN A369-33.7518.03610.7111.0020.89N

Atom 5560 CA GLN A369-33.0378.97011.5641.0021.49C

Atom 5562 CB GLN A369-32.78210.28010.8321.0021.58C

Atom 5565 CG GLN A369-32.07111.35911.6771.0021.20C

Atom 5568 CD GLN A369-30.63911.00611.9761.0020.04C

Atom 5569 OE1 GLN A369-30.28210.65013.1081.0019.10O

Atom 5570 NE2 GLN A369-29.80311.09510.9561.0018.75N

Atom 5573C GLN A369-33.7639.26512.8701.0022.21C

Atom 5574O GLN A369-33.1229.34313.9091.0022.41O

Atom 5576N GLU A370-35.0809.45512.8221.0023.05N

Atom 5577 CA GLU A370-35.8569.71814.0461.0023.71C

Atom 5579 CB GLU A370-37.32910.04113.7261.0024.04C

Atom 5582 CG GLU A370-37.48411.29312.8621.0026.84C

Atom 5585 CD GLU A370-38.89711.91012.8341.0030.36C

Atom 5586 OE1 GLU A370-39.88611.16112.5861.0031.90O

Atom 5587 OE2 GLU A370-38.99213.16413.0141.0031.62O

Atom 5588C GLU A370-35.7558.52314.9941.0023.60C

Atom 5589O GLU A370-35.5348.68916.1991.0023.33O

Atom 5591N ALA A371-35.9047.32214.4351.0023.72N

Atom 5592 CA ALA A371-35.7716.09115.2011.0023.91C

Atom 5594 CB ALA A371-35.9914.86814.3121.0023.76C

Atom 5598C ALA A371-34.3926.05115.8401.0024.20C

Atom 5599O ALA A371-34.2775.80417.0351.0024.54O

Atom 5601N LYS A372-33.3556.33315.0491.0024.38N

Atom 5602 CA LYS A372-31.9796.27315.5301.0024.39C

Atom 5604 CB LYS A372-30.9706.46614.3931.0024.43C

Atom 5607 CG LYS A372-30.6235.16413.6451.0025.20C

Atom 5610 CD LYS A372-29.1885.14913.0691.0026.09C

Atom 5613 CE LYS A372-29.1145.43711.5571.0027.01C

Atoms 5616 NZ LYS A372-29.0024.20010.7091.0026.82N

Atoms 5620C LYS A372-31.7177.26816.6451.0024.59C

Atom 5621O LYS A372-31.0966.90817.6271.0025.13O

Atom 5623N TRP A373-32.1818.50716.5201.0024.78N

Atom 5624 CA TRP A373-32.0069.47317.6101.0024.90C

Atom 5626 CB TRP A373-32.56510.86317.2661.0024.75C

Atom 5629 CG TRP A373-31.70111.67716.3381.0023.59C

Atom 5630 CD1 TRP A373-30.34411.66316.2591.0022.38C

Atom 5632 NE1 TRP A373-29.91512.53915.2981.0021.59N

Atom 5634 CE2 TRP A373-30.99913.16214.7441.0021.69C

Atom 5635 CD2 TRP A373-32.14712.64415.3761.0022.41C

Atom 5636 CE3 TRP A373-33.40913.11014.9761.0021.98C

Atom 5638 CZ3 TRP A373-33.48014.07213.9791.0022.08C

Atom 5640 CH2 TRP A373-32.31314.56713.3661.0022.31C

Atom 5642 CZ2 TRP A373-31.06714.12413.7361.0021.87C

Atom 5644C TRP A373-32.6788.97018.8811.0025.53C

Atom 5645O TRP A373-32.1019.07219.9721.0025.99O

Atoms 5647N LEU A374-33.8818.42018.7391.0025.84N

Atom 5648 CA LEU A374-34.6677.98019.8931.0026.29C

Atom 5650 CB LEU A374-36.0707.56219.4431.0026.32C

Atom 5653 CG LEU A374-37.2277.64620.4441.0026.39C

Atom 5655 CD1 LEU A374-38.4568.28619.7611.0026.95C

Atom 5659 CD2 LEU A374-37.5836.28121.0501.0026.24C

Atom 5663C LEU A374-33.9826.82420.6231.0026.77C

Atom 5664O LEU A374-33.9956.75821.8601.0026.95O

Atom 5666N TYR A375-33.3835.91919.8541.0027.23N

Atom 5667 CA TYR A375-32.7064.76120.4251.0027.74C

Atom 5669 CB TYR A375-32.1953.81419.3281.0027.78C

Atom 5672 CG TYR A375-31.5262.55619.8481.0028.74C

Atom 5673 CD1 TYR A375-32.2641.39420.0901.0029.61C

Atom 5675 CE1 TYR A375-31.652.23220.5731.0029.89C

Atom 5677 CZ TYR A375-30.287.22620.8171.0030.15C

Atom 5678 OH TYR A375-29.676-. 91721.2861.0030.57O

Atom 5680 CE2 TYR A375-29.5301.36720.5791.0030.05C

Atom 5682 CD2 TYR A375-30.1522.52220.0961.0029.74C

Atom 5684C TYR A375-31.5535.24821.2751.0027.97C

Atom 5685O TYR A375-31.4044.83722.4221.0028.00O

Atoms 5687N ASN A376-30.7636.15820.7191.0028.32N

Atom 5688 CA ASN A376-29.5316.59021.3681.0028.71C

Atom 5690 CB ASN A376-28.5697.16120.3291.0028.60C

Atom 5693 CG ASN A376-28.2156.15919.2551.0028.32C

Atoms 5694 OD1 ASN A376-27.9614.97719.5271.0025.72O

Atom 5695 ND2 ASN A376-28.1956.63118.0151.0029.29N

Atoms 5698C ASN A376-29.7287.61722.4841.0029.05C

Atom 5699O ASN A376-28.7528.02123.1361.0029.03O

Atom 5701N LYS A377-30.9778.02122.7161.0029.16N

Atom 5702 CA LYS A377-31.2549.17823.5491.0029.27C

Atom 5704 CB LYS A377-31.0518.87925.0501.0029.52C

Atom 5707 CG LYS A377-32.2028.11225.7231.0030.36C

Atom 5710 CD LYS A377-32.2026.63825.3401.0031.54C

Atom 5713 CE LYS A377-33.3225.86226.0311.0032.30C

Atom 5716 NZ LYS A377-33.5594.50925.4111.0032.13N

Atom 5720C LYS A377-30.33710.29923.0801.0028.92C

Atom 5721O LYS A377-29.59010.86723.8751.0028.94O

Atom 5723N SER A378-30.37710.57521.7761.0028.52N

Atom 5724 CA SER A378-29.65211.70021.2011.0028.30C

Atom 5726 CB SER A378-29.62311.62019.6781.0028.33C

Atom 5729 OG SER A378-28.91910.48219.2371.0029.36O

Atom 5731C SER A378-30.35512.97721.5941.0027.97C

Atom 5732O SER A378-31.48312.94722.1081.0027.91O

Atom 5734N THR A379-29.68414.09821.3441.0027.60N

Atom 5735 CA THR A379-30.25715.42221.5811.0027.24C

Atom 5737 CB THR A379-29.92915.95023.0021.0027.23C

Atom 5739 OG1 THR A379-28.51216.10223.1581.0026.85O

Atoms 5741 CG2 THR A379-30.46715.00724.0671.0027.48C

Atoms 5745C THR A379-29.73816.41420.5481.0026.83C

Atom 5746O THR A379-28.83417.19020.8441.0026.69O

Atom 5748N PRO A380-30.30516.39019.3311.0026.56N

Atom 5749 CA PRO A380-29.88417.31518.2781.0026.52C

Atom 5751 CB PRO A380-30.38016.64816.9921.0026.46C

Atom 5754 CG PRO A380-31.28115.53317.4081.0026.41C

Atom 5757 CD PRO A380-31.39515.50818.8871.0026.53C

Atom 5760C PRO A380-30.46918.72818.3861.0026.55C

Atom 5761O PRO A380-31.47218.96619.0631.0026.69O

Atoms 5762N THR A381-29.84019.66117.6921.0026.51N

Atom 5763 CA THR A381-30.29921.03417.6991.0026.51C

Atom 5765 CB THR A381-29.26121.95517.0331.0026.99C

Atom 5767 OG1 THR A381-28.91921.43115.7321.0027.65O

Atom 5769 CG2 THR A381-28.00322.08217.9301.0026.41C

Atom 5773C THR A381-31.63521.16716.9701.0026.06C

Atom 5774O THR A381-31.97220.34716.1121.0026.03O

Atom 5776N PHE A382-32.38622.21817.2941.0025.52N

Atom 5777 CA PHE A382-33.68122.43616.6541.0024.83C

Atom 5779 CB PHE A382-34.28423.79317.0111.0024.53C

Atom 5782 CG PHE A382-35.49524.11316.2111.0023.77C

Atom 5783 CD1 PHE A382-36.74523.71516.6371.0024.50C

Atom 5785 CE1 PHE A382-37.87323.97715.8781.0024.49C

Atom 5787 CZ PHE A382-37.74424.63014.6731.0024.41C

Atom 5789 CE2 PHE A382-36.49025.01414.2351.0023.88C

Atom 5791 CD2 PHE A382-35.38124.75214.9991.0023.29C

Atom 5793C PHE A382-33.54222.34215.1501.0024.49C

Atom 5794O PHE A382-34.36121.73114.4851.0024.32O

Atom 5796N ASP A383-32.49822.96914.6271.0024.42N

Atom 5797 CA ASP A383-32.25723.00513.1901.0024.19C

Atom 5799 CB ASP A383-31.10123.96612.8671.0024.21C

Atom 5802 CG ASP A383-31.47325.42313.0501.0023.72C

Atom 5803 OD1 ASP A383-32.63425.79412.8371.0025.60O

Atom 5804 OD2 ASP A383-30.59426.22013.3831.0024.03O

Atom 5805C ASP A383-31.98221.61212.5991.0024.06C

Atom 5806O ASP A383-32.39321.34211.4731.0024.00O

Atom 5808N ASP A384-31.29820.73913.3361.0023.78N

Atom 5809 CA ASP A384-31.07819.37912.8481.0024.11C

Atom 5811 CB ASP A384-29.98118.65113.6321.0024.54C

Atom 5814 CG ASP A384-28.57319.00913.1591.0026.32C

Atom 5815 OD1 ASP A384-28.44119.85212.2321.0028.55O

Atom 5816 OD2 ASP A384-27.59918.45113.7281.0027.18O

Atom 5817C ASP A384-32.35118.55012.9051.0023.83C

Atom 5818O ASP A384-32.67017.82511.9551.0024.24O

Atom 5820N TYR A385-33.07018.63714.0171.0023.31N

Atom 5821 CA TYR A385-34.29417.86114.1791.0022.89C

Atom 5823 CB TYR A385-34.83317.97915.6081.0022.86C

Atom 5826 CG TYR A385-36.14417.24515.8071.0022.65C

Atom 5827 CD1 TYR A385-36.16315.86816.0301.0022.36C

Atom 5829 CE1 TYR A385-37.35115.18916.2061.0022.77C

Atom 5831 CZ TYR A385-38.54515.88716.1461.0023.54C

Atom 5832 OH TYR A385-39.73315.21216.3091.0024.38O

Atom 5834 CE2 TYR A385-38.55417.25815.9131.0022.76C

Atom 5836 CD2 TYR A385-37.36017.92315.7441.0022.12C

Atom 5838C TYR A385-35.37518.29913.1901.0022.55C

Atom 5839O TYR A385-36.05017.46712.5841.0022.85O

Atom 5841N PHE A386-35.53719.60913.0421.0022.08N

Atom 5842 CA PHE A386-36.62620.15512.2481.0021.62C

Atom 5844 CB PHE A386-36.85721.62812.5681.0021.73C

Atom 5847 CG PHE A386-38.03322.20911.8511.0021.54C

Atom 5848 CD1 PHE A386-39.31121.93312.2731.0021.29C

Atom 5850 CE1 PHE A386-40.38022.44411.6231.0022.11C

Atom 5852 CZ PHE A386-40.19323.24010.5171.0023.28C

Atom 5854 CE2 PHE A386-38.92023.50210.0691.0023.10C

Atom 5856 CD2 PHE A386-37.85322.98910.7371.0022.15C

Atom 5858C PHE A386-36.36919.98710.7691.0021.09C

Atom 5859O PHE A386-37.27819.70010.0061.0020.91O

Atom 5861N GLY A387-35.12720.17710.3621.0020.68N

Atom 5862 CA GLY A387-34.74719.9178.9851.0020.43C

Atom 5865C GLY A387-35.15118.5218.5441.0019.95C

Atom 5866O GLY A387-35.55318.3277.3981.0020.24O

Atom 5868N ASN A388-35.03217.5549.4511.0019.12N

Atom 5869 CA ASN A388-35.45116.1829.2021.0018.73C

Atom 5871 CB ASN A388-34.74415.27210.2051.0018.90C

Atom 5874 CG ASN A388-34.86313.7959.8711.0018.35C

Atom 5875 OD1 ASN A388-34.16313.2848.9931.0017.24O

Atom 5876 ND2 ASN A388-35.71413.09210.6141.0017.01N

Atom 5879C ASN A388-36.96816.0339.3501.0018.65C

Atom 5880O ASN A388-37.62415.3708.5511.0018.82O

Atom 5882N ALA A389-37.52716.67010.3711.0018.38N

Atom 5883 CA ALA A389-38.92616.47710.7281.0018.02C

Atom 5885 CB ALA A389-39.20317.10712.0841.0017.83C

Atom 5889C ALA A389-39.94916.9669.7001.0017.90C

Atom 5890O ALA A389-41.09516.5449.7601.0017.74O

Atom 5892N TRP A390-39.58517.8608.7831.0018.11N

Atom 5893 CA TRP A390-40.54318.2547.7311.0018.46C

Atom 5895 CB TRP A390-40.45919.7377.3291.0018.59C

Atom 5898 CG TRP A390-39.14320.2246.8211.0019.26C

Atom 5899 CD1 TRP A390-38.22420.9477.5191.0020.64C

Atom 5901 NE1 TRP A390-37.13821.2246.7291.0020.62N

Atom 5903 CE2 TRP A390-37.35220.6945.4851.0019.57C

Atom 5904 CD2 TRP A390-38.60720.0665.5041.0019.15C

Atom 5905 CE3 TRP A390-39.06019.4484.3441.0020.13C

Atom 5907 CZ3 TRP A390-38.25419.4773.2241.0020.27C

Atom 5909 CH2 TRP A390-37.01720.1103.2391.0019.38C

Atom 5911 CZ2 TRP A390-36.54920.7244.3561.0019.49C

Atom 5913C TRP A390-40.40717.3436.5271.0018.73C

Atom 5914O TRP A390-41.36917.1435.7881.0018.32O

Atom 5916N LYS A391-39.20016.8066.3361.0019.30N

Atom 5917 CA LYS A391-38.96915.6925.4041.0019.70C

Atom 5919 CB LYS A391-37.45915.3925.2441.0019.92C

Atom 5922 CG LYS A391-36.81215.9533.9351.0022.08C

Atom 5925 CD LYS A391-35.25716.2174.0401.0023.92C

Atom 5928 CE LYS A391-34.91817.6984.4261.0024.43C

Atom 5931 NZ LYS A391-33.69917.9015.3071.0023.23N

Atom 5935C LYS A391-39.73114.4415.8611.0019.46C

Atom 5936O LYS A391-40.28413.7095.0321.0020.07O

Atom 5938N SER A392-39.79314.2027.1701.0018.95N

Atom 5939 CA SER A392-40.45512.9987.6661.0018.63C

Atom 5941 CB SER A392-39.85012.5089.0001.0018.75C

Atom 5944 OG SER A392-40.31413.23010.1261.0018.94O

Atom 5946C SER A392-41.96413.1527.7711.0018.20C

Atom 5947O SER A392-42.65412.1828.0311.0018.12O

Atom 5949N SER A393-42.47714.3607.5671.0018.07N

Atom 5950 CA SER A393-43.92914.5917.5561.0018.02C

Atom 5952 CB SER A393-44.22916.0787.5041.0018.08C

Atom 5955 OG SER A393-43.99516.5586.1921.0018.01O

Atom 5957C SER A393-44.59413.9716.3401.0017.87C

Atom 5958O SER A393-45.77813.6616.3721.0018.03O

Atom 5960N SER A394-43.82313.8415.2641.0017.69N

Atom 5961 CA SER A394-44.28413.3063.9891.0017.59C

Atom 5963 CB SER A394-45.32912.1804.1491.0017.61C

Atom 5966 OG SER A394-46.64812.6814.2941.0017.18O

Atom 5968C SER A394-44.82814.4153.1151.0017.42C

Atom 5969O SER A394-45.34514.1462.0241.0017.31O

Atom 5971N GLY A395-44.71115.6543.5921.0017.23N

Atom 5972 CA GLY A395-45.08816.8272.8071.0017.26C

Atom 5975C GLY A395-44.47816.7491.4151.0017.29C

Atom 5976O GLY A395-45.20316.653.4131.0018.06O

Atom 5978N PRO A396-43.14516.7541.3311.0016.72N

Atom 5979 CA PRO A396-42.58216.610.0061.0016.40C

Atom 5981 CB PRO A396-41.08016.549.2591.0016.62C

Atom 5984 CG PRO A396-40.90316.7491.7751.0017.11C

Atom 5987 CD PRO A396-42.15717.2522.2961.0016.87C

Atom 5990C PRO A396-43.05315.374-. 7481.0015.89C

Atom 5991O PRO A396-43.50115.498-1.8941.0015.90O

Atoms 5992N LEU A397-42.97314.197-. 1351.0015.27N

Atom 5993 CA LEU A397-43.28712.976-. 8861.0014.57C

Atoms 5995 CB LEU A397-43.33211.733-. 0081.0014.36C

Atom 5998 CG LEU A397-43.54110.431-. 7811.0014.02C

Atom 6000 CD1 LEU A397-42.6909.348-. 2061.0015.04C

Atom 6004 CD2 LEU A397-44.9859.976-. 8051.0013.75C

Atom 6008C LEU A397-44.61813.182-1.5421.0014.39C

Atom 6009O LEU A397-44.73612.999-2.7451.0014.57O

Atom 6011N GLN A398-45.60413.607-. 7511.0014.08N

Atom 6012 CA GLN A398-46.96213.828-1.2451.0013.91C

Atom 6014 CB GLN A398-47.86014.363-. 1361.0013.99C

Atom 6017 CG GLN A398-48.27413.321.9091.0014.01C

Atom 6020 CD GLN A398-49.18913.9021.9831.0013.41C

Atom 6021 OE1 GLN A398-49.94114.8471.7401.0014.65O

Atom 6022 NE2 GLN A398-49.12213.3443.1681.0012.17N

Atom 6025C GLN A398-47.01514.800-2.4031.0013.84C

Atom 6026O GLN A398-47.67714.547-3.3961.0013.46O

Atom 6028N LEU A399-46.31915.922-2.2721.0014.11N

Atom 6029 CA LEU A399-46.35916.942-3.3151.0014.37C

Atom 6031 CB LEU A399-45.90018.282-2.7561.0014.26C

Atom 6034 CG LEU A399-46.88218.830-1.7041.0014.44C

Atom 6036 CD1 LEU A399-46.25019.960-. 9191.0016.43C

Atom 6040 CD2 LEU A399-48.19119.304-2.3171.0012.20C

Atom 6044C LEU A399-45.58216.525-4.5781.0014.68C

Atom 6045O LEU A399-46.04316.784-5.6871.0014.70O

Atom 6047N ILE A400-44.44315.844-4.4191.0014.92N

Atom 6048 CA ILE A400-43.74815.221-5.5641.0015.08C

Atom 6050 CB ILE A400-42.54914.355-5.1291.0015.35C

Atom 6052 CG1 ILE A400-41.40615.254-4.6111.0016.83C

Atom 6055 CD1 ILE A400-40.23414.490-3.9581.0017.18C

Atom 6059 CG2 ILE A400-42.06013.486-6.2921.0014.03C

Atom 6063C ILE A400-44.68214.329-6.3581.0015.08C

Atom 6064O ILE A400-44.67214.362-7.5741.0015.18O

Atom 6066N PHE A401-45.47413.524-5.6501.0015.16N

Atom 6067 CA PHE A401-46.50112.674-6.2581.0014.90C

Atom 6069 CB PHE A401-47.05211.663-5.2401.0014.51C

Atom 6072 CG PHE A401-46.29410.378-5.2011.0012.92C

Atom 6073 CD1 PHE A401-46.7279.282-5.9311.0011.98C

Atom 6075 CE1 PHE A401-46.0328.093-5.9171.0011.20C

Atom 6077 CZ PHE A401-44.8817.985-5.1651.0012.03C

Atom 6079 CE2 PHE A401-44.4319.078-4.4281.0011.98C

Atom 6081 CD2 PHE A401-45.14310.263-4.4531.0012.09C

Atom 6083C PHE A401-47.64113.509-6.8061.0015.39C

Atom 6084O PHE A401-48.18313.215-7.8581.0015.51O

Atom 6086N ALA A402-48.02214.545-6.0801.0016.15N

Atom 6087 CA ALA A402-49.11015.393-6.5251.0016.90C

Atom 6089 CB ALA A402-49.39116.473-5.5051.0016.99C

Atom 6093C ALA A402-48.72216.003-7.8561.0017.50C

Atom 6094O ALA A402-49.54916.100-8.7701.0017.48O

Atom 6096N TYR A403-47.44416.367-7.9631.0018.28N

Atom 6097 CA TYR A403-46.91617.046-9.1421.0018.94C

Atom 6099 CB TYR A403-45.41217.252-9.0431.0019.03C

Atom 6102 CG TYR A403-44.82317.801-10.3141.0019.79C

Atom 6103 CD1 TYR A403-44.97319.138-10.6521.0020.80C

Atom 6105 CE1 TYR A403-44.43619.643-11.8271.0020.73C

Atom 6107 CZ TYR A403-43.75918.804-12.6741.0021.16C

Atom 6108 OH TYR A403-43.23119.283-13.8361.0022.98O

Atom 6110 CE2 TYR A403-43.60817.476-12.3701.0021.23C

Atom 6112 CD2 TYR A403-44.13716.980-11.1951.0020.93C

Atom 6114C TYR A403-47.19816.293-10.4131.0019.39C

Atom 6115O TYR A403-47.56716.904-11.4221.0019.57O

Atom 6117N PHE A404-47.02314.976-10.3761.0019.74N

Atom 6118 CA PHE A404-47.23914.177-11.5731.0020.35C

Atom 6120 CB PHE A404-46.53312.841-11.4661.0019.96C

Atom 6123 CG PHE A404-45.04812.971-11.3871.0018.81C

Atom 6124 CD1 PHE A404-44.29213.115-12.5281.0017.42C

Atom 6126 CE1 PHE A404-42.93513.239-12.4571.0017.24C

Atom 6128 CZ PHE A404-42.31213.237-11.2371.0017.40C

Atom 6130 CE2 PHE A404-43.05613.106-10.0931.0017.72C

Atom 6132 CD2 PHE A404-44.41312.975-10.1701.0017.93C

Atom 6134C PHE A404-48.71313.994-11.8941.0021.59C

Atom 6135O PHE A404-49.07213.717-13.0461.0021.71O

Atom 6137N ALA A405-49.57214.169-10.8961.0022.87N

Atom 6138 CA ALA A405-50.99013.939-11.0991.0024.06C

Atom 6140 CB ALA A405-51.60413.408-9.8331.0024.15C

Atom 6144C ALA A405-51.72415.192-11.5561.0025.21C

Atom 6145O ALA A405-52.87615.114-11.9391.0025.51O

Atom 6147N VAL A406-51.05616.336-11.5301.0026.52N

Atom 6148 CA VAL A406-51.71317.617-11.7591.0027.68C

Atom 6150 CB VAL A406-51.69418.406-10.4341.0027.60C

Atom 6152 CG1 VAL A406-51.65419.913-10.6631.0028.07C

Atom 6156 CG2 VAL A406-52.88318.009-9.5961.0027.41C

Atom 6160C VAL A406-51.09718.429-12.9251.0029.10C

Atom 6161O VAL A406-51.81019.104-13.6781.0028.53O

Atom 6163N VAL A407-49.77218.356-13.0591.0030.90N

Atom 6164 CA VAL A407-49.05219.003-14.1511.0032.15C

Atom 6166 CB VAL A407-47.57419.228-13.7771.0032.25C

Atom 6168 CG1 VAL A407-46.77019.780-14.9641.0032.22C

Atom 6172 CG2 VAL A407-47.49020.154-12.5831.0032.25C

Atom 6176C VAL A407-49.13418.160-15.4211.0033.36C

Atom 6177O VAL A407-48.68817.009-15.4541.0033.40O

Atom 6179N GLN A408-49.69318.767-16.4631.0034.93N

Atom 6180 CA GLN A408-49.93018.102-17.7491.0036.16C

Atom 6182 CB GLN A408-50.77919.016-18.6381.0036.63C

Atom 6185 CG GLN A408-51.62518.270-19.6721.0038.95C

Atom 6188 CD GLN A408-52.99118.930-19.8871.0041.80C

Atom 6189 OE1 GLN A408-53.73919.150-18.9211.0043.40O

Atom 6190 NE2 GLN A408-53.32319.244-21.1511.0041.68N

Atom 6193C GLN A408-48.63017.725-18.4701.0036.22C

Atom 6194O GLN A408-48.45616.588-18.9201.0035.86O

Atom 6196N ASN A409-47.72618.694-18.5781.0036.64N

Atom 6197 CA ASN A409-46.40018.441-19.1361.0036.85C

Atom 6199 CB ASN A409-46.13419.306-20.3731.0036.73C

Atom 6202 CG ASN A409-46.80818.752-21.6041.0036.19C

Atom 6203 OD1 ASN A409-46.17818.072-22.4201.0035.00O

Atom 6204 ND2 ASN A409-48.11018.994-21.7201.0034.99N

Atom 6207C ASN A409-45.31218.613-18.0951.0036.96C

Atom 6208O ASN A409-45.03219.720-17.6181.0036.81O

Atom 6210N ILE A410-44.71317.488-17.7341.0037.10N

Atom 6211 CA ILE A410-43.62517.508-16.7921.0037.27C

Atom 6213 CB ILE A410-43.26516.092-16.2951.0037.38C

Atom 6215 CG1 ILE A410-42.74515.209-17.4261.0037.84C

Atom 6218 CD1 ILE A410-42.41613.824-16.9851.0038.96C

Atom 6222 CG2 ILE A410-44.49115.437-15.6761.0037.67C

Atom 6226C ILE A410-42.46718.179-17.4921.0037.12C

Atom 6227O ILE A410-42.15017.839-18.6171.0036.87O

Atom 6229N LYS A411-41.89619.187-16.8511.0037.38N

Atom 6230 CA LYS A411-40.68019.813-17.3321.0037.73C

Atom 6232 CB LYS A411-40.75621.332-17.1711.0038.15C

Atom 6235 CG LYS A411-41.97921.962-17.8371.0039.89C

Atom 6238 CD LYS A411-41.79723.463-18.0801.0042.48C

Atom 6241 CE LYS A411-43.02924.069-18.7951.0044.22C

Atom 6244 NZ LYS A411-42.97725.576-18.9041.0045.31N

Atom 6248C LYS A411-39.56219.244-16.4891.0037.38C

Atom 6249O LYS A411-39.72119.112-15.2811.0037.28O

Atom 6251N LYS A412-38.44518.886-17.1221.0037.24N

Atom 6252 CA LYS A412-37.33318.243-16.4131.0036.95C

Atom 6254 CB LYS A412-36.28617.701-17.3841.0037.14C

Atom 6257 CG LYS A412-35.23316.818-16.7201.0037.89C

Atom 6260 CD LYS A412-34.33416.125-17.7571.0039.54C

Atom 6263 CE LYS A412-33.26317.068-18.3481.0040.08C

Atom 6266 NZ LYS A412-32.16117.399-17.3761.0040.16N

Atom 6270C LYS A412-36.66419.177-15.4191.0036.42C

Atom 6271O LYS A412-36.24618.728-14.3571.0036.56O

Atom 6273N GLU A413-36.57020.466-15.7441.0035.77N

Atom 6274 CA GLU A413-35.94821.423-14.8201.0035.38C

Atom 6276 CB GLU A413-35.68822.792-15.4891.0035.73C

Atom 6279 CG GLU A413-36.51024.013-14.9731.0037.10C

Atom 6282 CD GLU A413-35.62125.235-14.6331.0038.51C

Atom 6283 OE1 GLU A413-34.77825.125-13.7141.0039.24O

Atom 6284 OE2 GLU A413-35.76826.306-15.2661.0039.04O

Atom 6285C GLU A413-36.76021.551-13.5221.0034.43C

Atom 6286O GLU A413-36.19621.801-12.4601.0034.34O

Atom 6288N GLU A414-38.07421.360-13.6161.0033.45N

Atom 6289 CA GLU A414-38.95621.407-12.4521.0032.80C

Atom 6291 CB GLU A414-40.43521.425-12.8641.0032.83C

Atom 6294 CG GLU A414-40.92322.736-13.4781.0033.15C

Atom 6297 CD GLU A414-42.36022.668-14.0031.0033.82C

Atom 6298 OE1 GLU A414-42.87621.560-14.2311.0035.31O

Atom 6299 OE2 GLU A414-42.98523.727-14.2041.0033.98O

Atom 6300C GLU A414-38.71520.222-11.5361.0032.18C

Atom 6301O GLU A414-38.40720.409-10.3721.0032.25O

Atom 6303N ILE A415-38.86319.002-12.0441.0031.63N

Atom 6304 CA ILE A415-38.72517.819-11.1811.0031.28C

Atom 6306 CB ILE A415-39.13116.472-11.8521.0031.14C

Atom 6308 CG1 ILE A415-38.34916.204-13.1331.0031.13C

Atom 6311 CD1 ILE A415-38.78614.926-13.8361.0030.72C

Atom 6315 CG2 ILE A415-40.61116.454-12.1601.0031.12C

Atom 6319C ILE A415-37.31617.705-10.6361.0031.08C

Atom 6320O ILE A415-37.10517.188-9.5391.0031.22O

Atom 6322N GLU A416-36.34518.208-11.3811.0030.67N

Atom 6323 CA GLU A416-34.99818.270-10.8501.0030.55C

Atom 6325 CB GLU A416-34.01118.654-11.9551.0030.91C

Atom 6328 CG GLU A416-32.65417.967-11.8451.0032.55C

Atom 6331 CD GLU A416-31.80218.130-13.1091.0034.91C

Atom 6332 OE1 GLU A416-32.33718.563-14.1611.0035.53O

Atom 6333 OE2 GLU A416-30.59017.816-13.0521.0036.45O

Atom 6334C GLU A416-34.96219.249-9.6501.0029.74C

Atom 6335O GLU A416-34.14319.097-8.7381.0029.73O

Atom 6337N ASN A417-35.86420.234-9.6521.0028.69N

Atom 6338 CA ASN A417-36.06021.134-8.5031.0027.92C

Atom 6340 CB ASN A417-36.63222.477-8.9631.0027.75C

Atom 6343 CG ASN A417-35.57223.532-9.0951.0026.84C

Atom 6344 OD1 ASN A417-35.16024.132-8.1051.0024.88O

Atom 6345 ND2 ASN A417-35.11723.765-10.3181.0026.28N

Atom 6348C ASN A417-36.91720.580-7.3561.0027.41C

Atom 6349O ASN A417-36.65020.838-6.1871.0027.15O

Atom 6351N LEU A418-37.95519.834-7.6751.0027.09N

Atom 6352 CA LEU A418-38.69419.156-6.6281.0027.02C

Atom 6354 CB LEU A418-39.92118.423-7.2001.0026.95C

Atom 6357 CG LEU A418-41.03019.284-7.8261.0025.97C

Atom 6359 CD1 LEU A418-42.12718.429-8.4471.0024.88C

Atom 6363 CD2 LEU A418-41.62320.226-6.8031.0024.50C

Atom 6367C LEU A418-37.76318.196-5.8601.0027.26C

Atom 6368O LEU A418-37.83418.123-4.6441.0027.07O

Atom 6370N GLN A419-36.87317.494-6.5611.0027.67N

Atom 6371 CA GLN A419-35.92416.575-5.9091.0028.28C

Atom 6373 CB GLN A419-35.15515.758-6.9451.0028.36C

Atom 6376 CG GLN A419-35.74714.375-7.1461.0029.43C

Atom 6379 CD GLN A419-35.05213.573-8.2151.0029.76C

Atom 6380 OE1 GLN A419-34.35514.112-9.0661.0029.93O

Atom 6381 NE2 GLN A419-35.25212.270-8.1841.0031.33N

Atom 6384C GLN A419-34.92217.219-4.9471.0028.73C

Atom 6385O GLN A419-34.54016.608-3.9521.0028.90O

Atom 6387N LYS A420-34.49018.440-5.2401.0029.27N

Atom 6388 CA LYS A420-33.60819.166-4.3351.0029.81C

Atom 6390 CB LYS A420-32.75820.163-5.1291.0030.24C

Atom 6393 CG LYS A420-31.59219.513-5.8671.0031.75C

Atom 6396 CD LYS A420-31.25920.217-7.1831.0034.14C

Atom 6399 CE LYS A420-30.14019.463-7.9531.0036.21C

Atom 6402 NZ LYS A420-30.07319.759-9.4391.0036.76N

Atom 6406C LYS A420-34.37519.872-3.2041.0029.98C

Atom 6407O LYS A420-33.75920.547-2.3841.0030.44O

Atom 6409N TYR A421-35.70619.694-3.1621.0030.07N

Atom 6410 CA TYR A421-36.64620.309-2.1711.0029.73C

Atom 6412 CB TYR A421-36.29819.949-. 7121.0029.59C

Atom 6415 CG TYR A421-36.38618.468-. 4701.0030.57C

Atom 6416 CD1 TYR A421-37.58217.785-. 6431.0030.87C

Atom 6418 CE1 TYR A421-37.66516.414-. 4481.0031.28C

Atom 6420 CZ TYR A421-36.54915.705-. 0681.0031.90C

Atom 6421 OH TYR A421-36.62014.347.1241.0032.43O

Atom 6423 CE2 TYR A421-35.35516.354.1191.0032.68C

Atom 6425 CD2 TYR A421-35.27417.736-. 0951.0032.42C

Atom 6427C TYR A421-36.85021.816-2.3471.0029.24C

Atom 6428O TYR A421-36.70922.590-1.4011.0029.26O

Atom 6430N HIS A422-37.21922.214-3.5631.0028.65N

Atom 6431 CA HIS A422-37.54023.604-3.8591.0028.26C

Atom 6433 CB HIS A422-38.15023.715-5.2561.0028.33C

Atom 6436 CG HIS A422-38.29925.124-5.7481.0028.44C

Atom 6437 ND1 HIS A422-37.22525.904-6.1061.0028.97N

Atom 6439 CE1 HIS A422-37.66027.082-6.5201.0029.40C

Atom 6441 NE2 HIS A422-38.97727.090-6.4431.0028.14N

Atom 6443 CD2 HIS A422-39.39925.879-5.9651.0027.76C

Atom 6445C HIS A422-38.51124.147-2.8161.0027.74C

Atom 6446O HIS A422-39.35723.408-2.3101.0027.53O

Atom 6448N ASP A423-38.38425.437-2.5051.0027.12N

Atom 6449 CA ASP A423-39.18626.072-1.4541.0026.63C

Atom 6451 CB ASP A423-38.87727.575-1.3491.0027.05C

Atom 6454 CG ASP A423-37.45627.875-. 8511.0028.35C

Atom 6455 OD1 ASP A423-36.95127.121.0181.0030.99O

Atom 6456 OD2 ASP A423-36.86028.884-1.3221.0027.89O

Atom 6457C ASP A423-40.68925.883-1.6981.0025.71C

Atom 6458O ASP A423-41.48725.831-. 7491.0026.26O

Atom 6460N ILE A424-41.07525.781-2.9661.0024.01N

Atom 6461 CA ILE A424-42.47925.596-3.3271.0022.72C

Atom 6463 CB ILE A424-42.63925.391-4.8431.0022.40C

Atom 6465 CG1 ILE A424-44.02925.668-5.3181.0021.78C

Atom 6468 CD1 ILE A424-44.08625.499-6.7931.0022.22C

Atom 6472 CG2 ILE A424-42.34023.985-5.2551.0022.87C

Atom 6476C ILE A424-43.10324.442-2.5621.0021.91C

Atom 6477O ILE A424-44.23824.574-2.1151.0021.73O

Atom 6479N ILE A425-42.36523.334-2.3991.0021.23N

Atom 6480 CA ILE A425-42.85322.173-1.6341.0020.73C

Atom 6482 CB ILE A425-42.62220.820-2.3301.0020.10C

Atom 6484 CG1 ILE A425-41.15820.409-2.2901.0018.72C

Atom 6487 CD1 ILE A425-40.92319.075-2.9481.0018.27C

Atom 6491 CG2 ILE A425-43.14620.840-3.7411.0019.57C

Atom 6495C ILE A425-42.25222.060-. 2421.0021.21C

Atom 6496O ILE A425-42.81021.370.6131.0021.30O

Atom 6498N SER A426-41.12922.721-. 0021.0021.56N

Atom 6499 CA SER A426-40.49222.6201.2991.0022.23C

Atom 6501 CB SER A426-39.04323.0821.2341.0022.36C

Atom 6504 OG SER A426-38.97724.5011.3421.0024.09O

Atom 6506C SER A426-41.24223.4602.3341.0022.39C

Atom 6507O SER A426-41.39023.0513.4911.0022.95O

Atom 6509N ARG A427-41.70124.6431.9371.0022.08N

Atom 6510 CA ARG A427-42.33225.5412.9051.0021.87C

Atom 6512 CB ARG A427-42.46626.9552.3451.0021.99C

Atom 6515 CG ARG A427-41.17027.6962.4931.0023.36C

Atom 6518 CD ARG A427-40.95428.7271.4331.0026.07C

Atom 6521 NE ARG A427-39.68029.4071.6671.0028.18N

Atom 6523 CZ ARG A427-39.12730.298.8441.0029.21C

Atom 6524 NH1 ARG A427-39.72330.633-. 2981.0028.60N

Atom 6527 NH2 ARG A427-37.96230.8541.1731.0030.48N

Atom 6530C ARG A427-43.65125.0033.4341.0021.21C

Atom 6531O ARG A427-43.81724.8914.6451.0021.11O

Atoms 6533N PRO A428-44.57324.6222.5411.0020.52N

Atom 6534 CA PRO A428-45.78923.9993.0401.0020.27C

Atom 6536 CB PRO A428-46.41023.3691.7911.0020.44C

Atom 6539 CG PRO A428-45.86424.119.6661.0020.63C

Atom 6542 CD PRO A428-44.52124.6441.0741.0020.54C

Atom 6545C PRO A428-45.45022.9174.0501.0019.75C

Atom 6546O PRO A428-46.08922.8345.0951.0019.77O

Atom 6547N SER A429-44.42422.1233.7471.0018.97N

Atom 6548 CA SER A429-44.00821.0454.6361.0018.45C

Atom 6550 CB SER A429-42.95420.1803.9721.0018.35C

Atom 6553 OG SER A429-43.45219.7162.7331.0019.12O

Atom 6555C SER A429-43.51921.5255.9851.0017.97C

Atom 6556O SER A429-43.73320.8466.9681.0017.88O

Atoms 6558N HIS A430-42.87922.6896.0531.0017.73N

Atom 6559 CA HIS A430-42.59323.2897.3591.0017.71C

Atom 6561 CB HIS A430-41.93724.6687.2411.0017.97C

Atom 6564 CG HIS A430-40.55824.6636.6511.0018.87C

Atom 6565 ND1 HIS A430-39.94023.5246.1861.0019.85N

Atoms 6567 CE1 HIS A430-38.74623.8365.7091.0019.43C

Atom 6569 NE2 HIS A430-38.57325.1375.8381.0019.06N

Atoms 6571 CD2 HIS A430-39.69325.6816.4181.0019.32C

Atoms 6573C HIS A430-43.91423.4448.1311.0017.31C

Atom 6574O HIS A430-44.02323.0139.2871.0017.06O

Atom 6576N ILE A431-44.91324.0507.4751.0016.74N

Atom 6577 CA ILE A431-46.21824.3048.0911.0016.15C

Atom 6579 CB ILE A431-47.17425.0577.1741.0016.18C

Atom 6581 CG1 ILE A431-46.61326.4286.8011.0017.05C

Atom 6584 CD1 ILE A431-46.44127.3527.9941.0018.34C

Atom 6588 CG2 ILE A431-48.49625.2637.8601.0015.28C

Atom 6592C ILE A431-46.89923.0218.4761.0015.75C

Atom 6593O ILE A431-47.62422.9809.4451.0015.95O

Atoms 6595N PHE A432-46.66321.9697.7141.0015.59N

Atom 6596 CA PHE A432-47.19220.6528.0411.0015.52C

Atom 6598 CB PHE A432-46.83719.6836.9131.0015.23C

Atom 6601 CG PHE A432-47.45118.3187.0311.0015.98C

Atom 6602 CD1 PHE A432-48.32417.9728.0521.0016.55C

Atoms 6604 CE1 PHE A432-48.86716.7008.1021.0016.04C

Atom 6606 CZ PHE A432-48.55915.7747.1301.0015.29C

Atom 6608 CE2 PHE A432-47.71816.1076.1141.0015.37C

Atom 6610 CD2 PHE A432-47.17217.3646.0611.0016.74C

Atom 6612C PHE A432-46.64020.1919.3921.0015.54C

Atom 6613O PHE A432-47.38320.00610.3431.0015.37O

Atom 6615N ARG A433-45.32820.0419.4831.0015.98N

Atom 6616 CA ARG A433-44.69519.54210.7091.0016.20C

Atom 6618 CB ARG A433-43.17619.47610.5261.0015.85C

Atom 6621 CG ARG A433-42.41119.18311.8041.0016.11C

Atom 6624 CD ARG A433-42.84817.89012.4891.0015.70C

Atom 6627 NE ARG A433-42.81116.74711.5881.0015.64N

Atom 6629 CZ ARG A433-43.37715.57111.8381.0016.27C

Atom 6630 NH1 ARG A433-44.02915.35912.9651.0016.82N

Atom 6633 NH2 ARG A433-43.30214.59810.9481.0016.96N

Atom 6636C ARG A433-45.02920.41111.9351.0016.46C

Atom 6637O ARG A433-45.29619.89013.0311.0016.31O

Atom 6639N LEU A434-45.00621.73111.7241.0016.47N

Atom 6640 CA LEU A434-45.12322.70112.8001.0015.98C

Atom 6642 CB LEU A434-44.77124.11412.3031.0015.83C

Atom 6645 CG LEU A434-43.28724.48612.2181.0014.95C

Atom 6647 CD1 LEU A434-43.13025.91811.8261.0015.09C

Atom 6651 CD2 LEU A434-42.60024.28113.5361.0014.37C

Atom 6655C LEU A434-46.51722.66013.3871.0016.19C

Atom 6656O LEU A434-46.66922.56414.6041.0015.92O

Atom 6658N CYS A435-47.52922.71512.5201.0016.78N

Atom 6659 CA CYS A435-48.93622.59112.9401.0017.48C

Atom 6661 CB CYS A435-49.87022.61711.7261.0017.54C

Atom 6664 SG CYS A435-50.11024.23310.9851.0018.80S

Atom 6666C CYS A435-49.19221.29613.7081.0017.84C

Atom 6667O CYS A435-50.04321.25014.5971.0017.92O

Atom 6669N ASN A436-48.44620.25713.3331.0018.24N

Atom 6670 CA ASN A436-48.60318.91313.8461.0018.50C

Atom 6672 CB ASN A436-47.93617.94912.8671.0018.63C

Atom 6675 CG ASN A436-48.15616.48713.2131.0018.58C

Atom 6676 OD1 ASN A436-48.81016.12914.1851.0018.80O

Atom 6677 ND2 ASN A436-47.58815.63312.3981.0019.29N

Atom 6680C ASN A436-47.97518.75515.2101.0018.83C

Atom 6681O ASN A436-48.55118.15316.1151.0019.00O

Atom 6683N ASP A437-46.76319.25515.3511.0019.29N

Atom 6684 CA ASP A437-46.09719.17916.6341.0019.62C

Atom 6686 CB ASP A437-44.61519.52216.5101.0019.45C

Atom 6689 CG ASP A437-43.84918.48015.7341.0019.36C

Atom 6690 OD1 ASP A437-44.49117.58615.1581.0019.89O

Atom 6691 OD2 ASP A437-42.60818.54315.6991.0019.86O

Atom 6692C ASP A437-46.79920.10617.5971.0020.01C

Atom 6693O ASP A437-46.91619.79018.7791.0020.30O

Atom 6695N LEU A438-47.28821.23317.0921.0020.40N

Atom 6696 CA LEU A438-47.99622.17417.9401.0021.03C

Atom 6698 CB LEU A438-48.51023.36317.1261.0021.01C

Atom 6701 CG LEU A438-47.57524.56517.0781.0020.32C

Atom 6703 CD1 LEU A438-47.93825.52415.9521.0019.14C

Atom 6707 CD2 LEU A438-47.61125.26318.4151.0019.73C

Atoms 6711C LEU A438-49.15321.49618.6791.0021.81C

Atom 6712O LEU A438-49.27721.63319.9021.0021.55O

Atom 6714N ALA A439-49.97320.75417.9321.0022.76N

Atom 6715 CA ALA A439-51.13820.05518.4861.0023.58C

Atom 6717 CB ALA A439-51.90519.36017.3861.0023.57C

Atom 6721C ALA A439-50.74619.04219.5421.0024.47C

Atom 6722O ALA A439-51.38618.95120.5751.0024.63O

Atom 6724N SER A440-49.68518.29119.2761.0025.78N

Atom 6725 CA SER A440-49.24217.22720.1681.0026.84C

Atom 6727 CB SER A440-48.56616.13019.3531.0026.92C

Atom 6730 OG SER A440-47.32116.58218.8591.0027.46O

Atom 6732C SER A440-48.27017.69121.2441.0027.68C

Atom 6733O SER A440-47.93416.92322.1321.0028.00O

Atom 6735N ALA A441-47.82218.93521.1741.0028.83N

Atom 6736 CA ALA A441-46.76019.41922.0561.0029.73C

Atom 6738 CB ALA A441-46.52920.91021.8411.0029.84C

Atom 6742C ALA A441-46.98219.13223.5391.0030.57C

Atom 6743O ALA A441-46.30618.27424.0931.0030.50O

Atom 6745N SER A442-47.92919.82724.1721.0031.90N

Atom 6746 CA SER A442-47.99919.86225.6541.0032.95C

Atom 6748 CB SER A442-49.04320.87026.1691.0032.91C

Atom 6751 OG SER A442-50.33120.61425.6501.0033.50O

Atom 6753C SER A442-48.21918.49726.2891.0033.69C

Atom 6754O SER A442-47.75418.24627.3971.0033.59O

Atom 6756N ALA A443-48.92217.62325.5781.0034.93N

Atom 6757 CA ALA A443-49.05016.23125.9801.0035.81C

Atom 6759 CB ALA A443-49.98115.48825.0301.0035.72C

Atom 6763C ALA A443-47.66315.58025.9961.0036.71C

Atom 6764O ALA A443-47.19815.11527.0471.0036.94O

Atom 6766N GLU A444-46.99915.56724.8381.0037.47N

Atom 6767 CA GLU A444-45.68814.93024.7181.0037.93C

Atom 6769 CB GLU A444-45.16414.99623.2771.0037.99C

Atom 6772 CG GLU A444-45.95214.10022.3261.0039.24C

Atom 6775 CD GLU A444-45.41914.08020.8861.0041.03C

Atom 6776 OE1 GLU A444-44.61214.95820.5101.0042.16O

Atom 6777 OE2 GLU A444-45.82713.17820.1191.0042.36O

Atom 6778C GLU A444-44.69415.53425.7081.0038.09C

Atom 6779O GLU A444-43.92414.80326.3241.0038.17O

Atom 6781N ILE A445-44.73916.85125.8891.0038.41N

Atom 6782 CA ILE A445-43.82917.53026.8141.0038.75C

Atom 6784 CB ILE A445-43.80219.06526.5871.0038.69C

Atom 6786 CG1 ILE A445-43.31419.39625.1701.0038.18C

Atom 6789 CD1 ILE A445-43.70220.77524.7121.0037.58C

Atom 6793 CG2 ILE A445-42.90919.75327.6171.0038.26C

Atom 6797C ILE A445-44.24317.19428.2461.0039.35C

Atom 6798O ILE A445-45.03917.90128.8701.0039.44O

Atom 6800N ALA A446-43.69616.09228.7501.0040.02N

Atom 6801 CA ALA A446-44.08215.54030.0451.0040.51C

Atom 6803 CB ALA A446-43.81516.55231.1701.0040.55C

Atom 6807C ALA A446-45.55915.13030.0291.0040.86C

Atom 6808O ALA A446-46.40716.02130.1211.0040.77O

Atom 6810N ARG A447-45.92513.84229.8991.0041.31N

Atom 6811 CA ARG A447-45.07212.63329.6911.0041.58C

Atom 6813 CB ARG A447-45.27212.09228.2581.0041.84C

Atom 6816 CG ARG A447-46.66711.49527.9911.0042.69C

Atom 6819 CD ARG A447-46.77810.90126.5821.0043.92C

Atom 6822 NE ARG A447-47.76411.58925.7441.0045.34N

Atom 6824 CZ ARG A447-47.88711.43524.4201.0046.56C

Atom 6825 NH1 ARG A447-47.07710.62323.7421.0046.71N

Atom 6828 NH2 ARG A447-48.82812.10723.7571.0046.97N

Atom 6831C ARG A447-43.58112.72830.0541.0041.38C

Atom 6832O ARG A447-43.23112.74731.2381.0041.92O

Atom 6834N GLY A448-42.71012.73629.0511.0040.88N

Atom 6835 CA GLY A448-41.31213.12829.2341.0040.44C

Atom 6838C GLY A448-40.57913.31627.9151.0040.08C

Atom 6839O GLY A448-39.36413.48827.9011.0040.05O

Atom 6841N GLU A449-41.32313.33226.8091.0039.56N

Atom 6842 CA GLU A449-40.75013.13225.4861.0039.19C

Atom 6844 CB GLU A449-41.82712.66824.5021.0039.52C

Atom 6847 CG GLU A449-42.40311.29024.8101.0040.61C

Atom 6850 CD GLU A449-43.34810.78223.7151.0042.21C

Atom 6851 OE1 GLU A449-43.06811.01922.5031.0041.83O

Atom 6852 OE2 GLU A449-44.36810.14124.0821.0042.41O

Atom 6853C GLU A449-40.03714.36524.9211.0038.34C

Atom 6854O GLU A449-40.51115.49725.0311.0038.01O

Atom 6856N THR A450-38.90414.10624.2791.0037.37N

Atom 6857 CA THR A450-38.04715.13823.7261.0036.37C

Atom 6859 CB THR A450-36.60714.98524.2851.0036.39C

Atom 6861 OG1 THR A450-35.84616.15323.9821.0036.63O

Atom 6863 CG2 THR A450-35.88813.74923.7061.0036.52C

Atom 6867C THR A450-38.01315.10022.1901.0035.36C

Atom 6868O THR A450-37.17515.76421.5831.0035.43O

Atom 6870N ALA A451-38.91714.33821.5631.0033.98N

Atom 6871 CA ALA A451-38.92014.18220.0961.0032.81C

Atom 6873 CB ALA A451-39.03012.70819.7081.0032.99C

Atom 6877C ALA A451-40.04314.98719.4591.0031.46C

Atom 6878O ALA A451-41.05014.43218.9961.0031.06O

Atom 6880N ASN A452-39.84816.30219.4321.0029.88N

Atom 6881 CA ASN A452-40.88117.22518.9731.0028.81C

Atom 6883 CB ASN A452-41.95717.32920.0511.0028.57C

Atom 6886 CG ASN A452-42.96918.38019.7571.0028.30C

Atom 6887 OD1 ASN A452-42.62219.51719.4681.0029.35O

Atom 6888 ND2 ASN A452-44.23618.01819.8361.0028.36N

Atoms 6891C ASN A452-40.28518.59018.6411.0027.76C

Atom 6892O ASN A452-39.36519.01819.2961.0028.04O

Atom 6894N SER A453-40.80719.26917.6301.0026.77N

Atom 6895 CA SER A453-40.22620.53317.1821.0026.38C

Atom 6897 CB SER A453-40.91221.01515.9031.0026.40C

Atom 6900 OG SER A453-40.79620.04414.8761.0025.79O

Atom 6902C SER A453-40.25321.64318.2331.0026.12C

Atom 6903O SER A453-39.28022.36118.3851.0025.97O

Atom 6905N VAL A454-41.36821.78418.9421.0026.15N

Atom 6906 CA VAL A454-41.51822.78020.0221.0026.21C

Atom 6908 CB VAL A454-42.97522.81820.5321.0026.04C

Atom 6910 CG1 VAL A454-43.12223.78721.6941.0025.24C

Atom 6914 CG2 VAL A454-43.91323.19019.4011.0026.32C

Atom 6918C VAL A454-40.61722.45121.2111.0026.63C

Atom 6919O VAL A454-40.17323.32821.9591.0026.53O

Atom 6921N SER A455-40.37421.16021.3801.0027.21N

Atom 6922 CA SER A455-39.54120.65122.4371.0027.60C

Atom 6924 CB SER A455-39.67719.14122.4901.0027.31C

Atom 6927 OG SER A455-38.92218.62523.5451.0028.13O

Atom 6929C SER A455-38.09621.04522.1811.0028.29C

Atom 6930O SER A455-37.44521.62823.0431.0028.63O

Atom 6932N CYS A456-37.59920.74820.9881.0029.04N

Atom 6933 CA CYS A456-36.21921.08220.6401.0029.65C

Atom 6935 CB CYS A456-35.86820.53519.2561.0029.52C

Atom 6938 SG CYS A456-35.95918.73419.1631.0029.71S

Atom 6940C CYS A456-35.95522.58920.7101.0030.26C

Atom 6941O CYS A456-34.88723.00721.1621.0030.49O

Atom 6943N TYR A457-36.92423.39920.2831.0030.88N

Atom 6944 CA TYR A457-36.76724.85020.3081.0031.45C

Atom 6946 CB TYR A457-37.96725.55719.6481.0031.55C

Atom 6949 CG TYR A457-37.69126.99119.1781.0032.09C

Atom 6950 CD1 TYR A457-37.37827.26917.8431.0031.69C

Atom 6952 CE1 TYR A457-37.12828.56917.4181.0031.73C

Atom 6954 CZ TYR A457-37.18629.61318.3281.0032.84C

Atom 6955 OH TYR A457-36.94530.91717.9271.0033.81O

Atom 6957 CE2 TYR A457-37.49229.36419.6581.0032.72C

Atom 6959 CD2 TYR A457-37.74628.06420.0741.0032.44C

Atom 6961C TYR A457-36.57125.29521.7581.0031.99C

Atom 6962O TYR A457-35.64826.05322.0521.0031.98O

Atom 6964N MET A458-37.41924.79922.6611.0032.76N

Atom 6965 CA MET A458-37.21124.98724.1051.0033.37C

Atom 6967 CB MET A458-38.15124.09724.9211.0033.43C

Atom 6970 CG MET A458-39.57024.59325.0591.0033.70C

Atom 6973 SD MET A458-40.64123.31225.7371.0034.59S

Atom 6974 CE MET A458-39.70922.76327.1791.0034.71C

Atom 6978C MET A458-35.78424.64124.5171.0033.78C

Atom 6979O MET A458-35.10125.43725.1511.0033.73O

Atom 6981N ARG A459-35.34723.44524.1451.0034.46N

Atom 6982 CA ARG A459-34.05122.92624.5811.0035.15C

Atom 6984 CB ARG A459-33.87621.44724.1711.0035.68C

Atom 6987 CG ARG A459-32.49420.86424.5001.0037.23C

Atom 6990 CD ARG A459-32.49119.34524.7521.0039.80C

Atom 6993 NE ARG A459-33.14018.53823.7111.0042.88N

Atom 6995 CZ ARG A459-32.70418.40722.4531.0045.43C

Atom 6996 NH1 ARG A459-31.61519.06222.0351.0047.50N

Atom 6999 NH2 ARG A459-33.36617.62921.5951.0044.77N

Atom 7002C ARG A459-32.87823.74924.0721.0034.92C

Atom 7003O ARG A459-32.00724.10924.8491.0035.06O

Atom 7005N THR A460-32.85424.04722.7781.0034.96N

Atom 7006 CA THR A460-31.67424.67822.1631.0034.91C

Atom 7008 CB THR A460-31.49424.26320.6801.0034.88C

Atom 7010 OG1 THR A460-32.33025.06719.8411.0034.39O

Atom 7012 CG2 THR A460-31.82522.77620.4881.0035.44C

Atom 7016C THR A460-31.67226.21022.2581.0034.78C

Atom 7017O THR A460-30.67326.83721.9111.0034.92O

Atom 7019N LYS A461-32.78126.80622.7011.0034.41N

Atom 7020 CA LYS A461-32.81128.23123.0391.0034.25C

Atom 7022 CB LYS A461-33.92128.94722.2651.0034.56C

Atom 7025 CG LYS A461-33.71728.98620.7501.0035.84C

Atom 7028 CD LYS A461-32.51929.85920.3471.0037.64C

Atom 7031 CE LYS A461-32.23229.80418.8381.0038.44C

Atom 7034 NZ LYS A461-33.14130.67118.0271.0038.31N

Atom 7038C LYS A461-32.97428.47624.5441.0033.73C

Atom 7039O LYS A461-32.99429.62624.9831.0033.23O

Atom 7041N GLY A462-33.07827.39525.3211.0033.48N

Atom 7042 CA GLY A462-33.17327.46426.7841.0033.23C

Atom 7045C GLY A462-34.33228.32027.2391.0032.95C

Atom 7046O GLY A462-34.14429.25828.0041.0033.17O

Atom 7048N ILE A463-35.52828.00026.7571.0032.52N

Atom 7049 CA ILE A463-36.69428.84326.9711.0032.32C

Atom 7051 CB ILE A463-37.00629.72425.7341.0032.47C

Atom 7053 CG1 ILE A463-37.15228.86624.4631.0032.41C

Atom 7056 CD1 ILE A463-37.35929.67523.1911.0032.02C

Atom 7060 CG2 ILE A463-35.93730.81025.5711.0032.44C

Atom 7064C ILE A463-37.90228.00627.3091.0032.15C

Atom 7065O ILE A463-37.88626.79927.1451.0032.01O

Atom 7067N SER A464-38.95028.67027.7801.0032.27N

Atom 7068 CA SER A464-40.16328.00628.2391.0032.52C

Atom 7070 CB SER A464-40.96428.97429.1101.0032.65C

Atom 7073 OG SER A464-41.11230.22428.4571.0032.69O

Atom 7075C SER A464-41.03627.52227.0791.0032.53C

Atom 7076O SER A464-40.96828.06925.9861.0032.62O

Atom 7078N GLU A465-41.85726.50027.3321.0032.47N

Atom 7079 CA GLU A465-42.83626.01026.3531.0032.33C

Atom 7081 CB GLU A465-43.68924.86826.9351.0032.34C

Atom 7084 CG GLU A465-44.75624.31225.9741.0032.37C

Atom 7087 CD GLU A465-45.67523.27926.6111.0032.47C

Atom 7088 OE1 GLU A465-45.29722.65927.6301.0031.63O

Atom 7089 OE2 GLU A465-46.78523.08626.0741.0032.77O

Atom 7090C GLU A465-43.75827.12425.8641.0032.33C

Atom 7091O GLU A465-44.07827.18324.6761.0032.60O

Atom 7093N GLU A466-44.19628.00126.7671.0032.08N

Atom 7094 CA GLU A466-45.08529.09726.3801.0031.79C

Atom 7096 CB GLU A466-45.60629.83227.6241.0031.91C

Atom 7099 CG GLU A466-46.50331.04127.3041.0032.82C

Atom 7102 CD GLU A466-47.42631.47228.4521.0033.67C

Atom 7103 OE1 GLU A466-47.51930.75629.4781.0035.09O

Atom 7104 OE2 GLU A466-48.07732.53328.3121.0033.12O

Atom 7105C GLU A466-44.39230.05225.3861.0031.13C

Atom 7106O GLU A466-45.03230.60324.4921.0030.87O

Atom 7108N LEU A467-43.07730.19425.5311.0030.57N

Atom 7109 CA LEU A467-42.26531.10224.7081.0030.18C

Atom 7111 CB LEU A467-41.05531.60425.5241.0030.38C

Atom 7114 CG LEU A467-40.67433.08725.4631.0030.39C

Atom 7116 CD1 LEU A467-41.60833.90026.3621.0030.23C

Atom 7120 CD2 LEU A467-39.21433.30825.8721.0030.31C

Atom 7124C LEU A467-41.77330.40123.4391.0029.47C

Atom 7125O LEU A467-41.66031.01022.3821.0029.17O

Atom 7127N ALA A468-41.44529.12123.5621.0028.93N

Atom 7128 CA ALA A468-41.09528.31022.4041.0028.45C

Atom 7130 CB ALA A468-40.61326.93522.8301.0028.10C

Atom 7134C ALA A468-42.30628.19321.4941.0028.08C

Atom 7135O ALA A468-42.17928.32120.2851.0028.24O

Atom 7137N THR A469-43.47927.96422.0801.0027.58N

Atom 7138 CA THR A469-44.71927.87021.3221.0027.26C

Atom 7140 CB THR A469-45.92827.71022.2611.0027.28C

Atom 7142 OG1 THR A469-46.06326.33022.6271.0027.55O

Atom 7144 CG2 THR A469-47.22228.18521.5971.0027.34C

Atom 7148C THR A469-44.91629.09920.4491.0027.10C

Atom 7149O THR A469-45.17628.98919.2501.0027.11O

Atom 7151N GLU A470-44.77430.26721.0611.0026.88N

Atom 7152 CA GLU A470-44.94431.54220.3761.0026.84C

Atom 7154 CB GLU A470-44.83232.66321.4001.0027.07C

Atom 7157 CG GLU A470-45.35734.00320.9581.0028.47C

Atom 7160 CD GLU A470-45.14035.08722.0081.0030.51C

Atom 7161 OE1 GLU A470-45.02934.77523.2211.0031.53O

Atom 7162 OE2 GLU A470-45.08336.26921.6081.0032.59O

Atom 7163C GLU A470-43.92631.75019.2391.0026.48C

Atom 7164O GLU A470-44.26132.29618.1841.0026.29O

Atom 7166N SER A471-42.68631.31619.4521.0026.12N

Atom 7167 CA SER A471-41.66031.38618.4081.0025.85C

Atom 7169 CB SER A471-40.29630.93318.9411.0025.96C

Atom 7172 OG SER A471-39.65631.93919.7111.0026.53O

Atom 7174C SER A471-42.03630.52917.2081.0025.35C

Atom 7175O SER A471-41.76130.89916.0671.0025.43O

Atom 7177N VAL A472-42.65329.38117.4821.0024.95N

Atom 7178 CA VAL A472-43.09728.45116.4381.0024.65C

Atom 7180 CB VAL A472-43.48527.05517.0241.0024.57C

Atom 7182 CG1 VAL A472-44.25726.22216.0161.0023.23C

Atom 7186 CG2 VAL A472-42.23226.30917.4941.0023.83C

Atom 7190C VAL A472-44.25229.03915.6311.0024.71C

Atom 7191O VAL A472-44.36928.77614.4401.0024.63O

Atom 7193N MET A473-45.07329.86616.2691.0024.79N

Atom 7194 CA MET A473-46.14330.59115.5651.0024.94C

Atom 7196 CB MET A473-47.05931.26616.5761.0025.11C

Atom 7199 CG MET A473-47.68330.33517.5601.0025.11C

Atom 7202 SD MET A473-48.96729.39116.7801.0025.35S

Atom 7203 CE MET A473-50.06429.16318.1891.0026.11C

Atom 7207C MET A473-45.61331.67214.6051.0024.86C

Atom 7208O MET A473-46.13231.84913.5131.0024.57O

Atom 7210N ASN A474-44.58932.40515.0321.0024.89N

Atom 7211 CA ASN A474-43.95133.38314.1661.0025.00C

Atom 7213 CB ASN A474-43.00934.27814.9661.0025.12C

Atom 7216 CG ASN A474-43.70034.96616.1271.0025.77C

Atom 7217 OD1 ASN A474-43.05835.31217.1141.0026.96O

Atom 7218 ND2 ASN A474-45.01535.16316.0211.0026.31N

Atom 7221C ASN A474-43.19532.70713.0241.0024.84C

Atom 7222O ASN A474-42.97933.31311.9731.0025.07O

Atom 7224N LEU A475-42.79231.45513.2271.0024.46N

Atom 7225 CA LEU A475-42.21830.67112.1421.0024.06C

Atom 7227 CB LEU A475-41.59629.36712.6531.0024.27C

Atom 7230 CG LEU A475-40.30729.07211.8861.0025.08C

Atom 7232 CD1 LEU A475-39.20730.00012.4191.0025.89C

Atom 7236 CD2 LEU A475-39.88727.62211.9851.0025.33C

Atom 7240C LEU A475-43.27830.36511.0851.0023.26C

Atom 7241O LEU A475-43.01830.4799.8841.0022.90O

Atom 7243N ILE A476-44.47129.97811.5341.0022.53N

Atom 7244 CA ILE A476-45.54429.63210.6061.0021.93C

Atom 7246 CB ILE A476-46.77329.01711.3081.0021.58C

Atom 7248 CG1 ILE A476-46.49927.55011.6641.0021.32C

Atom 7251 CD1 ILE A476-47.55226.90212.5981.0020.33C

Atom 7255 CG2 ILE A476-47.99429.10410.4281.0020.46C

Atom 7259C ILE A476-45.92630.8879.8531.0022.07C

Atom 7260O ILE A476-46.00730.8698.6261.0022.47O

Atom 7262N ASP A477-46.12231.98210.5841.0021.81N

Atom 7263 CA ASP A477-46.48333.2459.9701.0021.56C

Atom 7265 CB ASP A477-46.64334.33711.0321.0021.89C

Atom 7268 CG ASP A477-47.96234.21711.8171.0023.39C

Atom 7269 OD1 ASP A477-48.85433.44111.3751.0024.41O

Atom 7270 OD2 ASP A477-48.10334.90212.8751.0023.80O

Atom 7271C ASP A477-45.42533.6268.9471.0021.06C

Atom 7272O ASP A477-45.75933.9137.7951.0020.78O

Atoms 7274N GLU A478-44.15633.5919.3611.0020.63N

Atom 7275 CA GLU A478-43.02733.9198.4671.0020.45C

Atoms 7277 CB GLU A478-41.68033.7939.2001.0020.66C

Atom 7280 CG GLU A478-40.42234.0448.3391.0022.27C

Atom 7283 CD GLU A478-39.10733.5799.0181.0024.72C

Atom 7284 OE1 GLU A478-38.55334.3679.8171.0026.19O

Atom 7285 OE2 GLU A478-38.61932.4428.7451.0025.66O

Atom 7286C GLU A478-43.04133.0427.2171.0019.54C

Atom 7287O GLU A478-42.87933.5446.1021.0019.02O

Atom 7289N THR A479-43.25031.7437.4131.0018.76N

Atom 7290 CA THR A479-43.35830.8086.2941.0018.45C

Atom 7292 CB THR A479-43.50329.3396.7741.0018.26C

Atom 7294 OG1 THR A479-42.33428.9557.4941.0017.30O

Atom 7296 CG2 THR A479-43.66928.3945.5921.0017.93C

Atom 7300C THR A479-44.50431.1735.3141.0018.39C

Atom 7301O THR A479-44.28031.2004.1031.0018.58O

Atom 7303N TRP A480-45.70931.4575.8181.0017.85N

Atom 7304 CA TRP A480-46.80131.9094.9421.0017.44C

Atom 7306 CB TRP A480-48.08632.2255.7281.0017.67C

Atom 7309 CG TRP A480-48.96931.0425.8881.0017.09C

Atom 7310 CD1 TRP A480-48.99630.1956.9361.0016.76C

Atom 7312 NE1 TRP A480-49.91429.2166.7241.0017.08N

Atom 7314 CE2 TRP A480-50.50129.4105.5071.0017.86C

Atom 7315 CD2 TRP A480-49.93030.5594.9541.0017.15C

Atom 7316 CE3 TRP A480-50.35630.9803.6961.0018.31C

Atom 7318 CZ3 TRP A480-51.33730.2443.0391.0019.10C

Atom 7320 CH2 TRP A480-51.89729.1073.6221.0018.83C

Atom 7322 CZ2 TRP A480-51.49328.6734.8551.0018.86C

Atom 7324C TRP A480-46.42633.1244.0971.0017.10C

Atom 7325O TRP A480-46.82433.2152.9431.0017.22O

Atom 7327N LYS A481-45.67534.0624.6591.0016.60N

Atom 7328 CA LYS A481-45.27535.2153.8861.0016.23C

Atom 7330 CB LYS A481-44.56636.2434.7471.0016.42C

Atom 7333 CG LYS A481-45.41736.9545.7691.0016.42C

Atom 7336 CD LYS A481-44.55537.9796.5051.0016.40C

Atom 7339 CE LYS A481-45.19938.5047.7821.0016.66C

Atom 7342 NZ LYS A481-44.18438.7178.8461.0016.72N

Atom 7346C LYS A481-44.35734.7822.7671.0015.94C

Atom 7347O LYS A481-44.45135.2911.6741.0016.09O

Atom 7349N LYS A482-43.46133.8493.0341.0015.98N

Atom 7350 CA LYS A482-42.55933.3691.9961.0016.30C

Atom 7352 CB LYS A482-41.40932.5632.5941.0016.51C

Atom 7355 CG LYS A482-40.35433.4453.2861.0017.46C

Atom 7358 CD LYS A482-39.48632.6474.2411.0018.48C

Atom 7361 CE LYS A482-38.62533.5485.0961.0018.94C

Atom 7364 NZ LYS A482-37.86532.7736.1291.0020.40N

Atom 7368C LYS A482-43.29632.561.9381.0016.40C

Atom 7369O LYS A482-42.94132.614-. 2291.0016.85O

Atom 7371N MET A483-44.32831.8241.3321.0016.57N

Atom 7372 CA MET A483-45.14931.100.3661.0016.67C

Atom 7374 CB MET A483-46.12830.1561.0571.0016.55C

Atom 7377 CG MET A483-45.49628.9231.6751.0016.50C

Atom 7380 SD MET A483-46.71527.6842.1941.0017.39S

Atom 7381 CE MET A483-47.93728.7043.0251.0017.27C

Atom 7385C MET A483-45.92832.069-. 4951.0017.06C

Atom 7386O MET A483-46.02731.867-1.6881.0017.17O

Atom 7388N ASN A484-46.48333.110.1181.0017.72N

Atom 7389 CA ASN A484-47.30534.093-. 5871.0018.35C

Atom 7391 CB ASN A484-47.86135.129.3971.0018.26C

Atom 7394 CG ASN A484-48.99434.6011.2481.0017.35C

Atom 7395 OD1 ASN A484-49.59733.577.9341.0017.54O

Atom 7396 ND2 ASN A484-49.30435.3172.3311.0014.10N

Atoms 7399C ASN A484-46.54134.839-1.6771.0019.51C

Atom 7400O ASN A484-47.12335.250-2.6851.0019.49O

Atom 7402N LYS A485-45.24335.035-1.4631.0020.86N

Atom 7403 CA LYS A485-44.39435.681-2.4561.0022.12C

Atom 7405 CB LYS A485-43.07036.092-1.8231.0022.08C

Atom 7408 CG LYS A485-42.22937.060-2.6411.0023.09C

Atom 7411 CD LYS A485-40.78337.072-2.1091.0025.38C

Atom 7414 CE LYS A485-40.09838.460-2.1351.0026.12C

Atom 7417 NZ LYS A485-38.94338.555-3.0861.0026.61N

Atom 7421C LYS A485-44.16434.743-3.6561.0023.36C

Atom 7422O LYS A485-44.12035.191-4.8021.0023.00O

Atom 7424N GLU A486-44.02733.442-3.4001.0024.99N

Atom 7425 CA GLU A486-43.90232.479-4.4911.0026.35C

Atom 7427 CB GLU A486-43.62731.061-3.9781.0026.55C

Atom 7430 CG GLU A486-42.98530.130-5.0331.0028.29C

Atom 7433 CD GLU A486-41.46630.324-5.1911.0031.11C

Atom 7434 OE1 GLU A486-40.98130.466-6.3411.0032.07O

Atom 7435 OE2 GLU A486-40.74430.335-4.1591.0033.04O

Atom 7436C GLU A486-45.15732.501-5.3621.0027.13C

Atom 7437O GLU A486-45.06432.618-6.5831.0027.57O

Atom 7439N LYS A487-46.32532.422-4.7391.0028.12N

Atom 7440 CA LYS A487-47.58232.378-5.4851.0029.12C

Atom 7442 CB LYS A487-48.78832.260-4.5421.0029.21C

Atom 7445 CG LYS A487-50.16732.296-5.2351.0028.57C

Atom 7448 CD LYS A487-50.40331.040-6.0361.0027.91C

Atom 7451 CE LYS A487-51.61531.141-6.9361.0028.38C

Atom 7454 NZ LYS A487-52.87431.460-6.2111.0028.03N

Atom 7458C LYS A487-47.75633.603-6.3521.0030.18C

Atom 7459O LYS A487-48.30833.514-7.4461.0030.21O

Atom 7461N LEU A488-47.29534.743-5.8441.0031.64N

Atom 7462 CA LEU A488-47.42236.026-6.5321.0032.65C

Atom 7464 CB LEU A488-47.42637.144-5.4941.0032.43C

Atom 7467 CG LEU A488-48.09138.446-5.9071.0032.50C

Atom 7469 CD1 LEU A488-49.59338.288-5.9431.0032.66C

Atom 7473 CD2 LEU A488-47.70739.554-4.9431.0033.38C

Atom 7477C LEU A488-46.28636.242-7.5421.0033.99C

Atom 7478O LEU A488-46.53636.539-8.7051.0033.72O

Atom 7480N GLY A489-45.04636.045-7.0911.0035.85N

Atom 7481 CA GLY A489-43.84536.361-7.8741.0037.37C

Atom 7484C GLY A489-43.27835.221-8.7091.0038.76C

Atom 7485O GLY A489-42.41434.467-8.2501.0039.06O

Atom 7487N GLY A490-43.76035.119-9.9471.0040.26N

Atom 7488 CA GLY A490-43.28534.130-10.9271.0041.03C

Atom 7491C GLY A490-42.19333.194-10.4361.0041.61C

Atom 7492O GLY A490-41.01033.547-10.4231.0041.62O

Atom 7494N SER A491-42.59031.996-10.0231.0042.17N

Atom 7495 CA SER A491-41.61930.962-9.6621.0042.54C

Atom 7497 CB SER A491-42.27929.909-8.7411.0042.63C

Atom 7500 OG SER A491-43.45129.345-9.2941.0042.44O

Atom 7502C SER A491-41.03230.349-10.9521.0042.50C

Atom 7503O SER A491-41.11730.961-12.0301.0042.57O

Atoms 7505N LEU A492-40.40529.177-10.8431.0042.18N

Atom 7506 CA LEU A492-40.18528.333-12.0211.0041.96C

Atom 7508 CB LEU A492-39.11027.270-11.7821.0042.39C

Atom 7511 CG LEU A492-37.69527.671-11.3531.0044.21C

Atom 7513 CD1 LEU A492-36.78326.438-11.4981.0045.26C

Atom 7517 CD2 LEU A492-37.12028.896-12.1291.0045.51C

Atoms 7521C LEU A492-41.47927.610-12.3561.0040.88C

Atom 7522O LEU A492-41.71327.244-13.5041.0040.78O

Atom 7524N PHE A493-42.30827.409-11.3391.0039.61N

Atom 7525 CA PHE A493-43.50026.595-11.4601.0038.85C

Atom 7527 CB PHE A493-43.78325.911-10.1241.0038.62C

Atom 7530 CG PHE A493-42.72524.937-9.7131.0037.16C

Atom 7531 CD1 PHE A493-42.90123.587-9.9161.0035.26C

Atom 7533 CE1 PHE A493-41.93422.698-9.5461.0034.86C

Atom 7535 CZ PHE A493-40.76923.143-8.9661.0035.09C

Atom 7537 CE2 PHE A493-40.57424.482-8.7591.0035.45C

Atom 7539 CD2 PHE A493-41.54925.374-9.1301.0036.36C

Atom 7541C PHE A493-44.71427.412-11.8901.0038.62C

Atom 7542O PHE A493-44.75628.621-11.7021.0038.86O

Atom 7544N ALA A494-45.69826.731-12.4691.0038.32N

Atom 7545 CA ALA A494-46.97727.337-12.8431.0038.09C

Atom 7547 CB ALA A494-47.65826.486-13.9061.0038.17C

Atom 7551C ALA A494-47.89127.479-11.6231.0037.76C

Atom 7552O ALA A494-48.03926.541-10.8451.0038.15O

Atoms 7554N LYS A495-48.54128.629-11.4841.0037.15N

Atom 7555 CA LYS A495-49.32128.947-10.2701.0036.53C

Atoms 7557 CB LYS A495-50.11630.258-10.4771.0036.90C

Atom 7560 CG LYS A495-49.23531.524-10.5821.0037.72C

Atoms 7563 CD LYS A495-50.06132.826-10.5851.0038.87C

Atom 7566 CE LYS A495-49.14034.065-10.6651.0039.78C

Atoms 7569 NZ LYS A495-49.78635.369-10.2821.0039.78N

Atoms 7573C LYS A495-50.23827.809-9.7241.0035.25C

Atoms 7574O LYS A495-50.26127.563-8.5231.0034.91O

Atom 7576N PRO A496-50.97827.107-10.5991.0033.76N

Atom 7577 CA PRO A496-51.84626.015-10.1621.0032.74C

Atom 7579 CB PRO A496-52.22225.340-11.4741.0032.99C

Atom 7582 CG PRO A496-52.33726.470-12.3851.0033.75C

Atom 7585 CD PRO A496-51.19627.400-12.0221.0033.83C

Atom 7588C PRO A496-51.19424.998-9.2671.0031.24C

Atom 7589O PRO A496-51.82224.522-8.3311.0031.54O

Atom number 7590N PHE A497-49.95424.642-9.5661.0029.40N

Atom 7591 CA PHE A497-49.22923.726-8.7081.0027.76C

Atom 7593 CB PHE A497-48.16222.948-9.4741.0027.62C

Atom 7596 CG PHE A497-47.35122.040-8.5971.0026.33C

Atom 7597 CD1 PHE A497-47.94420.969-7.9741.0024.96C

Atom 7599 CE1 PHE A497-47.21820.151-7.1561.0025.04C

Atom 7601 CZ PHE A497-45.87520.396-6.9401.0024.79C

Atom 7603 CE2 PHE A497-45.27421.457-7.5491.0024.73C

Atom 7605 CD2 PHE A497-46.01022.282-8.3661.0025.48C

Atom 7607C PHE A497-48.59224.407-7.4941.0026.59C

Atom 7608O PHE A497-48.36123.738-6.5001.0026.77O

Atom 7610N VAL A498-48.29125.704-7.5351.0024.83N

Atom 7611 CA VAL A498-47.86926.338-6.2891.0023.86C

Atom 7613 CB VAL A498-47.18127.722-6.4551.0023.47C

Atom 7615 CG1 VAL A498-48.16328.755-6.7591.0024.57C

Atom 7619 CG2 VAL A498-46.15127.690-7.5511.0023.54C

Atom 7623C VAL A498-49.09426.396-5.3551.0022.97C

Atom 7624O VAL A498-48.97826.130-4.1611.0023.39O

Atom 7626N GLU A499-50.26826.687-5.9031.0021.68N

Atom 7627 CA GLU A499-51.47326.719-5.1061.0020.84C

Atom 7629 CB GLU A499-52.67727.136-5.9301.0020.99C

Atom 7632 CG GLU A499-53.95727.352-5.0991.0021.25C

Atom 7635 CD GLU A499-53.93028.630-4.2651.0021.77C

Atom 7636 OE1 GLU A499-52.98229.448-4.3831.0020.74O

Atom 7637 OE2 GLU A499-54.87628.812-3.4761.0022.76O

Atom 7638C GLU A499-51.76625.371-4.4971.0020.35C

Atom 7639O GLU A499-52.13725.308-3.3181.0020.78O

Atom 7641N THR A500-51.62924.286-5.2641.0019.40N

Atom 7642 CA THR A500-51.89422.970-4.6671.0018.94C

Atom 7644 CB THR A500-51.99321.782-5.6831.0018.96C

Atom 7646 OG1 THR A500-50.70821.475-6.2021.0019.44O

Atom 7648 CG2 THR A500-52.99122.071-6.8351.0018.75C

7652C THR A500-50.89522.674-3.5261.0018.20C atoms

Atom 7653O THR A500-51.28022.100-2.5191.0017.68O

7655N ALA A501-49.64623.119-3.6661.0017.49N atoms

Atom 7656 CA ALA A501-48.66323.021-2.5931.0017.18C

Atom 7658 CB ALA A501-47.34823.563-3.0511.0016.98C

Atom 7662C ALA A501-49.12023.770-1.3381.0017.38C

Atom 7663O ALA A501-49.09823.219-. 2301.0017.45O

Atom 7665N ILE A502-49.51725.031-1.5081.0017.29N

Atom 7666 CA ILE A502-49.97125.857-. 3861.0017.07C

Atom 7668 CB ILE A502-50.35327.304-. 8461.0017.09C

Atom 7670 CG1 ILE A502-49.09228.069-1.2861.0017.17C

Atom 7673 CD1 ILE A502-49.34529.345-2.1161.0016.25C

Atom 7677 CG2 ILE A502-51.11028.076.2651.0016.14C

Atom 7681C ILE A502-51.15525.168.2851.0017.24C

Atom 7682O ILE A502-51.26525.1631.5161.0017.03O

Atom 7684N ASN A503-52.02224.559-. 5221.0017.32N

Atom 7685 CA ASN A503-53.16723.823.0221.0017.75C

Atom 7687 CB ASN A503-53.98623.221-1.1211.0017.70C

Atom 7690 CG ASN A503-54.76024.261-1.8881.0018.41C

Atom 7691 OD1 ASN A503-55.05825.334-1.3821.0018.94O

Atom 7692 ND2 ASN A503-55.10723.939-3.1191.0020.42N

Atom 7695C ASN A503-52.80322.7271.0751.0017.74C

Atom 7696O ASN A503-53.61922.3871.9491.0017.96O

Atom 7698N LEU A504-51.58922.185.9931.0017.23N

Atom 7699 CA LEU A504-51.10521.2491.9941.0017.10C

Atom 7701 CB LEU A504-49.74520.6861.5831.0017.28C

Atom 7704 CG LEU A504-49.21319.5282.4261.0017.29C

Atom 7706 CD1 LEU A504-49.57018.1961.7621.0017.22C

Atom 7710 CD2 LEU A504-47.70819.6862.6161.0016.83C

Atom 7714C LEU A504-50.97121.9393.3471.0016.97C

Atom 7715O LEU A504-51.23721.3304.3791.0016.84O

7717N ALA A505-50.53523.2013.3301.0016.90N

Atom 7718 CA ALA A505-50.43324.0154.5401.0016.68C

Atom 7720 CB ALA A505-49.73925.3094.2431.0016.54C

Atom 7724C ALA A505-51.82624.2815.0741.0016.77C

Atom 7725O ALA A505-52.08724.1236.2661.0016.80O

Atom 7727N ARG A506-52.72624.6644.1721.0016.82N

Atom 7728 CA ARG A506-54.12824.8754.5211.0016.84C

Atom 7730 CB ARG A506-54.94425.2743.2861.0016.86C

Atom 7733 CG ARG A506-54.64926.6612.7951.0016.27C

Atom 7736 CD ARG A506-55.58627.0901.7261.0015.26C

Atom 7739 NE ARG A506-55.24028.4361.2731.0015.31N

Atom 7741 CZ ARG A506-54.74428.758.0821.0014.28C

Atom 7742 NH1 ARG A506-54.51927.856-. 8561.0014.12N

Atom 7745 NH2 ARG A506-54.47130.018-. 1761.0015.94N

Atom 7748C ARG A506-54.73223.6315.1221.0016.96C

Atom 7749O ARG A506-55.48023.7076.0891.0016.71O

Atom 7751N GLN A507-54.41522.4814.5421.0017.37N

Atom 7752 CA GLN A507-54.96221.2335.0481.0017.87C

Atom 7754 CB GLN A507-54.71220.0754.0871.0017.80C

Atom 7757 CG GLN A507-55.29318.7404.5711.0017.24C

Atom 7760 CD GLN A507-56.77718.8054.8601.0016.23C

Atom 7761 OE1 GLN A507-57.50619.5854.2501.0016.66O

Atom 7762 NE2 GLN A507-57.23317.9805.7901.0014.96N

Atom 7765C GLN A507-54.40120.8906.4231.0018.28C

Atom 7766O GLN A507-55.14820.4197.2871.0018.53O

Atom 7768N SER A508-53.09621.1136.6091.0018.50N

Atom 7769 CA SER A508-52.43520.9247.9081.0018.54C

Atom 7771 CB SER A508-50.97921.3857.8561.0018.40C

Atom 7774 OG SER A508-50.25920.6946.8571.0018.51O

Atom 7776C SER A508-53.14721.7528.9421.0018.78C

Atom 7777O SER A508-53.53521.27810.0061.0018.33O

Atom 7779N HIS A509-53.32423.0148.5991.0019.37N

Atom 7780 CA HIS A509-54.01423.9229.4661.0019.92C

Atom 7782 CB HIS A509-54.12625.2958.8181.0020.07C

Atom 7785 CG HIS A509-53.00026.1889.1741.0019.82C

Atom 7786 ND1 HIS A509-52.07926.6318.2551.0019.73N

Atom 7788 CE1 HIS A509-51.18727.3838.8661.0020.25C

Atom 7790 NE2 HIS A509-51.48527.42610.1491.0021.66N

Atom 7792 CD2 HIS A509-52.61526.68210.3681.0020.98C

Atom 7794C HIS A509-55.38923.4489.8391.0020.41C

Atom 7795O HIS A509-55.82123.69410.9341.0020.22O

Atom 7797N CYS A510-56.09322.8088.9181.0021.33N

Atom 7798 CA CYS A510-57.47022.3969.1891.0022.03C

Atom 7800 CB CYS A510-58.27822.3837.8941.0021.90C

Atom 7803 SG CYS A510-58.52224.0557.2701.0021.93S

Atom 7805C CYS A510-57.52721.0549.9081.0022.60C

Atom 7806O CYS A510-58.42320.82210.7061.0022.23O

Atom 7808N THR A511-56.55320.1949.6271.0023.67N

Atom 7809 CA THR A511-56.42118.92010.3051.0024.81C

Atom 7811 CB THR A511-55.43718.0009.5651.0024.70C

Atom 7813 OG1 THR A511-56.07117.4858.3941.0024.45O

Atom 7815 CG2 THR A511-55.00316.84410.4481.0024.23C

Atom 7819C THR A511-55.96519.08611.7561.0026.22C

Atom 7820O THR A511-56.68518.71712.6791.0026.12O

Atom 7822N TYR A512-54.77519.64311.9591.0028.08N

Atom 7823 CA TYR A512-54.17719.65713.2981.0029.63C

Atom 7825 CB TYR A512-52.66319.78313.2381.0029.67C

Atom 7828 CG TYR A512-52.11718.57912.5601.0029.56C

Atom 7829 CD1 TYR A512-51.96517.39513.2461.0029.66C

Atom 7831 CE1 TYR A512-51.50716.27312.6141.0030.94C

Atom 7833 CZ TYR A512-51.21716.32611.2631.0032.04C

Atom 7834 OH TYR A512-50.75715.20910.6081.0033.78O

Atom 7836 CE2 TYR A512-51.39017.49210.5571.0031.29C

Atom 7838 CD2 TYR A512-51.84718.60011.2051.0030.53C

Atom 7840C TYR A512-54.81220.67614.2061.0031.11C

Atom 7841O TYR A512-55.49420.27715.1391.0031.34O

Atom 7843N HIS A513-54.58321.96913.9661.0032.89N

Atoms 7844 CA HIS A513-55.50523.02314.4421.0034.48C

Atom 7846 CB HIS A513-56.37223.46113.2251.0035.13C

Atom 7849 CG HIS A513-57.70424.10813.5291.0037.10C

Atom 7850 ND1 HIS A513-58.26525.04012.6781.0038.69N

Atom 7852 CE1 HIS A513-59.44225.41613.1511.0039.23C

Atom 7854 NE2 HIS A513-59.67824.75114.2681.0038.18N

Atom 7856 CD2 HIS A513-58.61523.91514.5191.0038.17C

Atom 7858C HIS A513-56.33722.50315.6101.0035.00C

Atom 7859O HIS A513-56.30223.07416.7121.0035.48O

Atom 7861N ASN A514-57.07921.41915.3511.0035.23N

Atom 7862 CA ASN A514-57.93420.76816.3471.0035.46C

Atom 7864 CB ASN A514-58.34219.34315.9031.0035.39C

Atom 7867 CG ASN A514-59.38319.34514.7861.0034.01C

Atom 7868 OD1 ASN A514-59.33620.18513.8961.0033.36O

Atom 7869 ND2 ASN A514-60.31518.40614.8331.0031.13N

Atom 7872C ASN A514-57.46420.75117.8181.0036.15C

Atom 7873O ASN A514-56.39720.21118.1531.0036.13O

Atoms 7875N GLY A515-58.27721.43018.6401.0036.95N

Atom 7876 CA GLY A515-58.42721.23520.0791.0037.43C

Atom 7879C GLY A515-59.72420.47020.3811.0038.18C

Atom 7880O GLY A515-59.63619.41821.0211.0038.57O

Atom 7882N ASP A516-60.93020.92119.9691.0038.73N

Atom 7883 CA ASP A516-61.24922.19419.2931.0039.26C

Atom 7885 CB ASP A516-61.60721.90417.8451.0039.51C

Atom 7888 CG ASP A516-60.52322.29116.8941.0042.32C

Atom 7889 OD1 ASP A516-59.61323.08417.2861.0045.56O

Atom 7890 OD2 ASP A516-60.57821.79715.7401.0045.52O

Atom 7891C ASP A516-62.46622.91319.8841.0039.38C

Atom 7892O ASP A516-63.03222.45420.8801.0039.74O

Atom 7894N ALA A517-62.85024.03819.2591.0039.40N

Atom 7895 CA ALA A517-64.14024.75219.4811.0039.50C

Atom 7897 CB ALA A517-65.11724.40318.3331.0039.27C

Atom 7901C ALA A517-64.83724.56620.8631.0039.90C

Atom 7902O ALA A517-64.17324.42821.8991.0039.89O

Atom 7904N HIS A518-66.17524.61720.8761.0040.33N

Atom 7905 CA HIS A518-66.97324.11222.0161.0040.73C

Atom 7907 CB HIS A518-68.09125.09222.3961.0041.22C

Atom 7910 CG HIS A518-67.57826.41922.8661.0043.58C

Atom 7911 ND1 HIS A518-67.42626.72524.2071.0045.88N

Atoms 7913 CE1 HIS A518-66.93827.95024.3201.0046.42C

Atom 7915 NE2 HIS A518-66.76028.44623.1021.0046.25N

Atom 7917 CD2 HIS A518-67.14527.50622.1741.0045.24C

Atoms 7919C HIS A518-67.52622.72521.6551.0040.17C

Atom 7920O HIS A518-68.73822.50121.5711.0040.02O

Atom 7922N THR A519-66.58121.81221.4481.0039.64N

Atom 7923 CA THR A519-66.80820.46620.9181.0039.16C

Atom 7925 CB THR A519-67.41420.46919.4531.0039.16C

Atom 7927 OG1 THR A519-66.84721.52918.6651.0039.04O

Atom 7929 CG2 THR A519-68.94220.63319.4801.0038.82C

Atom 7933C THR A519-65.42819.77120.9781.0038.85C

Atom 7934O THR A519-64.39120.43320.8781.0038.66O

Atom 7936N SER A520-65.40718.45521.1701.0038.37N

Atom 7937 CA SER A520-64.16017.74521.5001.0038.08C

Atom 7939 CB SER A520-64.51416.32021.9311.0038.06C

Atom 7942 OG SER A520-64.56015.47520.8051.0038.66O

Atom 7944C SER A520-63.13617.77120.3271.0037.86C

Atom 7945O SER A520-63.42018.36919.2891.0037.50O

Atom 7947N PRO A521-61.94817.12220.4821.0037.98N

Atom 7948 CA PRO A521-60.94417.17019.3791.0037.92C

Atom 7950 CB PRO A521-59.67416.52719.9871.0037.87C

Atom 7953 CG PRO A521-60.09115.91921.3301.0038.28C

Atom 7956 CD PRO A521-61.57716.13721.5261.0038.13C

Atom 7959C PRO A521-61.43216.44618.1101.0037.96C

Atom 7960O PRO A521-61.76917.11817.1401.0038.09O

Atom 7961N ASP A522-61.48315.10818.1071.0038.07N

Atom 7962 CA ASP A522-62.35114.39317.1611.0038.14C

Atom 7964 CB ASP A522-62.13212.87717.2041.0038.31C

Atom 7967 CG ASP A522-60.76912.45616.6401.0039.45C

Atom 7968 OD1 ASP A522-60.16013.20015.8271.0039.72O

Atom 7969 OD2 ASP A522-60.30211.36117.0251.0041.59O

Atom 7970C ASP A522-63.76014.78017.5911.0037.92C

Atom 7971O ASP A522-63.90815.60818.4741.0038.01O

Atoms 7973N GLU A523-64.79914.23916.9741.0037.79N

Atom 7974 CA GLU A523-66.15014.81817.1211.0037.83C

Atom 7976 CB GLU A523-66.61814.91918.5911.0037.85C

Atom 7979 CG GLU A523-66.34613.67819.4831.0039.40C

Atom 7982 CD GLU A523-66.91613.80220.9311.0041.49C

Atom 7983 OE1 GLU A523-67.71414.73721.2071.0042.81O

Atom 7984 OE2 GLU A523-66.56612.95721.8001.0042.04O

Atoms 7985C GLU A523-66.24216.20316.4301.0037.51C

Atom 7986O GLU A523-67.33816.75116.2831.0037.70O

Atoms 7988N LEU A524-65.09716.77516.0431.0037.03N

Atoms 7989 CA LEU A524-65.04417.86315.0671.0036.58C

Atoms 7991 CB LEU A524-64.17419.02215.5591.0036.56C

Atoms 7994 CG LEU A524-63.96320.22514.6241.0036.35C

Atoms 7996 CD1 LEU A524-63.40021.37615.4181.0035.74C

Atom 8000 CD2 LEU A524-65.24220.68113.9101.0036.53C

Atom 8004C LEU A524-64.47817.28713.7821.0036.20C

Atom 8005O LEU A524-65.10617.36312.7331.0036.14O

Atom 8007N THR A525-63.29816.68613.8691.0035.83N

Atom 8008 CA THR A525-62.75615.93512.7481.0035.66C

Atom 8010 CB THR A525-61.58515.01513.1731.0035.48C

Atom 8012 OG1 THR A525-60.77615.67814.1521.0035.55O

Atom 8014 CG2 THR A525-60.72014.64111.9781.0034.73C

Atom 8018C THR A525-63.87515.09812.1231.0035.89C

Atom 8019O THR A525-64.04015.09510.9091.0035.98O

Atom 8021N ARG A526-64.66714.42012.9541.0036.06N

Atom 8022 CA ARG A526-65.73913.57412.4481.0036.18C

Atom 8024 CB ARG A526-66.34012.71813.5551.0036.56C

Atom 8027 CG ARG A526-67.41611.75413.0541.0038.35C

Atom 8030 CD ARG A526-67.78110.70214.0921.0041.00C

Atom 8033 NE ARG A526-67.74011.20715.4701.0043.08N

Atom 8035 CZ ARG A526-68.63712.03316.0241.0044.51C

Atom 8036 NH1 ARG A526-69.68112.50015.3361.0044.46N

Atom 8039 NH2 ARG A526-68.47612.40617.2881.0045.02N

Atom 8042C ARG A526-66.83414.38411.7741.0035.68C

Atom 8043O ARG A526-67.25314.03510.6751.0035.84O

Atom 8045N LYS A527-67.30915.44712.4241.0035.06N

Atom 8046 CA LYS A527-68.28516.34311.7801.0034.61C

Atom 8048 CB LYS A527-68.68017.52812.6831.0034.74C

Atom 8051 CG LYS A527-69.81817.22513.6511.0035.40C

Atom 8054 CD LYS A527-70.30118.45214.4411.0035.99C

Atom 8057 CE LYS A527-71.28018.02115.5561.0036.42C

Atom 8060 NZ LYS A527-71.65219.09516.5301.0036.31N

Atom 8064C LYS A527-67.72316.86010.4571.0033.77C

Atom 8065O LYS A527-68.37716.7639.4231.0033.75O

Atom 8067N ARG A528-66.50117.38810.4991.0032.71N

Atom 8068 CA ARG A528-65.84017.9299.3101.0031.79C

Atom 8070 CB ARG A528-64.42518.4649.6441.0031.74C

Atom 8073 CG ARG A528-64.41919.84410.3301.0030.90C

Atom 8076 CD ARG A528-63.02120.43910.5271.0029.75C

Atom 8079 NE ARG A528-63.09821.74511.1901.0029.55N

Atom 8081 CZ ARG A528-62.05622.51311.5281.0029.96C

Atom 8082 NH1 ARG A528-60.80122.14511.2841.0029.74N

Atom 8085 NH2 ARG A528-62.26923.67712.1301.0030.71N

Atom 8088C ARG A528-65.79616.9048.1721.0030.99C

Atom 8089O ARG A528-66.22617.2067.0681.0030.97O

Atom 8091N VAL A529-65.31315.6948.4501.0030.12N

Atom 8092 CA VAL A529-65.23914.6317.4381.0029.43C

Atom 8094 CB VAL A529-64.55713.3547.9721.0029.39C

Atom 8096 CG1 VAL A529-64.78512.1877.0231.0028.89C

Atoms 8100 CG2 VAL A529-63.06213.5898.1861.0029.44C

Atom 8104C VAL A529-66.60914.2436.8871.0028.95C

Atom 8105O VAL A529-66.75514.0165.6901.0029.09O

Atom 8107N LEU A530-67.61514.1537.7441.0028.18N

Atom 8108 CA LEU A530-68.95613.8747.2461.0027.72C

Atom 8110 CB LEU A530-69.97113.7158.3951.0027.75C

Atom 8113 CG LEU A530-70.33412.2748.7751.0027.36C

Atom 8115 CD1 LEU A530-69.09611.4159.0501.0026.86C

Atom 8119 CD2 LEU A530-71.27312.2799.9681.0027.14C

Atom 8123C LEU A530-69.40114.9636.2561.0027.16C

Atom 8124O LEU A530-69.86114.6525.1611.0027.42O

Atom 8126N SER A531-69.23016.2296.6351.0026.21N

Atom 8127 CA SER A531-69.73017.3595.8531.0025.12C

Atom 8129 CB SER A531-69.51918.6576.6181.0025.01C

Atom 8132 OG SER A531-68.16718.7916.9851.0023.94O

Atom 8134C SER A531-69.05517.4764.5071.0024.48C

Atom 8135O SER A531-69.68717.8863.5381.0024.14O

Atom 8137N VAL A532-67.77417.1154.4611.0023.89N

Atom 8138 CA VAL A532-66.96217.2263.2461.0023.53C

Atom 8140 CB VAL A532-65.47017.4373.5751.0023.09C

Atom 8142 CG1 VAL A532-64.63317.3552.3481.0022.32C

Atom 8146 CG2 VAL A532-65.26818.7734.1981.0023.07C

Atom 8150C VAL A532-67.10016.0282.3161.0023.67C

Atom 8151O VAL A532-67.13716.2091.0991.0023.58O

Atom 8153N ILE A533-67.18714.8242.8861.0023.85N

Atom 8154 CA ILE A533-67.17213.5782.1071.0024.08C

Atom 8156 CB ILE A533-66.17212.5552.6911.0024.10C

Atom 8158 CG1 ILE A533-64.74513.0792.6311.0023.47C

Atom 8161 CD1 ILE A533-64.17813.0831.2551.0023.42C

Atom 8165 CG2 ILE A533-66.25411.2311.9321.0024.56C

Atom 8169C ILE A533-68.52212.8591.9901.0024.27C

Atom 8170O ILE A533-68.99112.620.8871.0024.34O

Atom 8172N THR A534-69.13312.4873.1111.0024.57N

Atom 8173 CA THR A534-70.27911.5643.0721.0024.92C

Atom 8175 CB THR A534-70.20010.5224.2071.0024.93C

Atom 8177 OG1 THR A534-70.49111.1495.4581.0025.28O

Atom 8179 CG2 THR A534-68.8049.8854.2571.0024.75C

Atom 8183C THR A534-71.67312.2093.0831.0025.00C

Atom 8184O THR A534-72.60111.6462.5221.0024.94O

Atom 8186N GLU A535-71.82113.3743.7081.0025.26N

Atom 8187 CA GLU A535-73.13214.0243.8331.0025.34C

Atom 8189 CB GLU A535-73.33314.5235.2551.0025.44C

Atom 8192 CG GLU A535-73.75313.4246.1961.0025.80C

Atom 8195 CD GLU A535-74.30713.9637.4681.0025.72C

Atom 8196 OE1 GLU A535-75.37513.4877.8811.0024.50O

Atom 8197 OE2 GLU A535-73.67814.8778.0391.0027.03O

Atom 8198C GLU A535-73.36315.1792.8591.0025.26C

Atom 8199O GLU A535-72.68616.2062.9391.0025.02O

Atom 8201N PRO A536-74.35115.0301.9591.0025.25N

Atom 8202 CA PRO A536-74.65516.1111.0501.0025.18C

Atom 8204 CB PRO A536-75.66115.484.0761.0025.15C

Atom 8207 CG PRO A536-75.82514.077.4761.0024.98C

Atom 8210 CD PRO A536-75.36313.9651.8681.0025.26C

Atom 8213C PRO A536-75.28917.2651.8011.0025.30C

Atom 8214O PRO A536-75.82617.0702.8831.0025.57O

Atom 8215N ILE A537-75.21318.4581.2301.0025.36N

Atom 8216 CA ILE A537-75.80719.6381.8271.0025.34C

Atom 8218 CB ILE A537-75.20120.9181.2211.0025.14C

Atom 8220 CG1 ILE A537-73.78721.1311.7441.0024.32C

Atom 8223 CD1 ILE A537-73.22822.4721.4061.0023.22C

Atom 8227 CG2 ILE A537-76.03022.1311.5691.0025.54C

Atom 8231C ILE A537-77.31319.6031.6111.0025.67C

Atom 8232O ILE A537-77.78619.132.5791.0025.47O

Atom 8234N LEU A538-78.07120.0882.5861.0026.22N

Atom 8235 CA LEU A538-79.51420.0512.4671.0026.65C

Atom 8237 CB LEU A538-80.21320.5253.7491.0026.78C

Atom 8240 CG LEU A538-80.16219.6094.9891.0026.64C

Atom 8242 CD1 LEU A538-81.21820.0336.0071.0026.16C

Atom 8246 CD2 LEU A538-80.34618.1384.6331.0026.12C

Atom 8250C LEU A538-79.92520.8811.2621.0027.08C

Atom 8253N PRO A539-80.78620.306.4141.0028.03N

Atom 8254 CA PRO A539-81.11720.855-. 8881.0028.44C

Atom 8256 CB PRO A539-82.09319.828-1.4491.0028.40C

Atom 8259 CG PRO A539-82.79319.328-. 2531.0028.30C

Atom 8262 CD PRO A539-81.72019.228.7871.0028.11C

Atom 8265C PRO A539-81.81322.194-. 8041.0028.89C

Atom 8266O PRO A539-82.39622.535.2261.0028.97O

Atom 8267N PHE A540-81.77422.932-1.9061.0029.32N

Atom 8268 CA PHE A540-82.38024.245-1.9621.0029.50C

Atom 8270 CB PHE A540-82.14624.874-3.3261.0029.56C

Atom 8273 CG PHE A540-82.75726.227-3.4631.0029.75C

Atom 8274 CD1 PHE A540-83.87426.429-4.2551.0029.47C

Atom 8276 CE1 PHE A540-84.44127.681-4.3641.0029.46C

Atom 8278 CZ PHE A540-83.90128.743-3.6741.0029.81C

Atom 8280 CE2 PHE A540-82.79128.553-2.8771.0030.21C

Atom 8282 CD2 PHE A540-82.22927.300-2.7701.0030.17C

Atom 8284C PHE A540-83.86524.129-1.7221.0029.66C

Atom 8285O PHE A540-84.56823.551-2.5451.0029.66O

Atom 8287N GLU A541-84.33724.673-. 6011.0029.90N

Atom 8288 CA GLU A541-85.76124.605-. 2331.0030.06C

Atom 8290 CB GLU A541-85.95123.7241.0171.0030.15C

Atom 8293 CG GLU A541-87.41123.3611.3671.0030.64C

Atom 8296 CD GLU A541-88.09124.3512.3221.0031.35C

Atom 8297 OE1 GLU A541-87.46825.3702.6801.0032.67O

Atom 8298 OE2 GLU A541-89.25424.1142.7191.0030.48O

Atom 8299C GLU A541-86.31526.011-. 0101.0029.89C

Atom 8300O GLU A541-86.83526.636-. 9361.0029.71O

Atom 8302N LEU B17-69.666-25.3252.2271.0033.20N

Atom 8303 CA LEU B17-69.356-25.417.7551.0033.49C

Atom 8305 CB LEU B17-70.240-26.475.0481.0033.44C

Atom 8308 CG LEU B17-70.077-27.986.3281.0033.60C

Atom 8310 CD1 LEU B17-71.285-28.778-., 2171.0032.76C

Atom 8314 CD2 LEU B17-68.763-28.553-., 2301.0033.21C

Atom 8318C LEU B17-69.513-24.044.0551.0033.54C

Atom 8319O LEU B17-70.550-23.380.1951.0033.77O

Atom 8323N LEU B18-68.481-23.637-. 6961.0033.44N

Atom 8324 CA LEU B18-68.476-22.362-1.4541.0033.07C

Atom 8326 CB LEU B18-67.029-21.960-1.8401.0033.21C

Atom 8329 CG LEU B18-66.065-21.488-. 7211.0034.06C

Atom 8331 CD1 LEU B18-64.607-21.351-1.2351.0034.51C

Atom 8335 CD2 LEU B18-66.516-20.164-., 0611.0033.43C

Atoms 8339C LEU B18-69.379-22.400-2.7141.0032.37C

Atom 8340O LEU B18-69.710-21.355-3.2741.0032.29O

Atom 8342N SER B19-69.765-23.597-3.1531.0031.62N

Atom 8343 CA SER B19-70.711-23.749-4.2531.0031.16C

Atom 8345 CB SER B19-70.443-25.067-5.0331.0031.09C

Atom 8348 OG SER B19-70.977-26.243-4.4211.0029.36O

Atom 8350C SER B19-72.168-23.663-3.7591.0031.45C

Atom 8351O SER B19-73.076-23.432-4.5511.0031.13O

Atom 8353N SER B20-72.386-23.824-2.4511.0031.91N

Atom 8354 CA SER B20-73.749-23.900-1.8791.0032.34C

Atom 8356 CB SER B20-73.706-24.122-. 3571.0032.35C

Atom 8359 OG SER B20-73.393-25.473-. 0551.0032.34O

Atom 8361C SER B20-74.601-22.670-2.2041.0032.69C

Atom 8362O SER B20-74.072-21.600-2.4871.0032.89O

Atom 8364N ASP B21-75.921-22.831-2.1191.0033.13N

Atom 8365 CA ASP B21-76.874-21.901-2.7451.0033.40C

Atom 8367 CB ASP B21-78.179-22.628-3.0451.0033.64C

Atom 8370 CG ASP B21-77.943-23.883-3.8281.0035.35C

Atom 8371 OD1 ASP B21-77.031-23.866-4.6841.0038.26O

Atom 8372 OD2 ASP B21-78.631-24.890-3.5901.0037.55O

Atoms 8373C ASP B21-77.141-20.649-1.9401.0033.23C

Atom 8374O ASP B21-78.039-20.616-1.1061.0032.91O

Atom 8376N THR B22-76.348-19.621-2.2291.0033.46N

Atom 8377 CA THR B22-76.443-18.307-1.5931.0033.79C

Atom 8379 CB THR B22-76.460-18.378-. 0161.0033.74C

Atom 8381 OG1 THR B22-75.426-19.250.4601.0032.97O

Atom 8383 CG2 THR B22-77.805-18.838.5351.0033.55C

Atom 8387C THR B22-75.217-17.479-2.0181.0034.24C

Atom 8388O THR B22-74.102-17.988-1.8921.0033.95O

Atom 8390N ASP B23-75.361-16.248-2.5431.0034.99N

Atom 8391 CA ASP B23-76.603-15.620-3.1031.0035.61C

Atom 8393 CB ASP B23-77.242-16.538-4.1701.0035.51C

Atom 8396 CG ASP B23-76.196-17.236-5.0341.0036.08C

Atom 8397 OD1 ASP B23-75.084-16.685-5.1941.0035.58O

Atom 8398 OD2 ASP B23-76.473-18.344-5.5411.0037.65O

Atom 8399C ASP B23-77.662-15.083-2.0971.0036.10C

Atom 8400O ASP B23-78.644-15.770-1.7991.0036.13O

Atom 8402N GLU B24-77.487-13.845-1.6161.0036.74N

Atom 8403 CA GLU B24-78.358-13.316-. 5431.0037.59C

Atom 8405 CB GLU B24-77.765-13.666.8381.0037.88C

Atom 8408 CG GLU B24-77.624-15.1731.1201.0038.51C

Atom 8411 CD GLU B24-77.314-15.5102.5881.0039.48C

Atom 8412 OE1 GLU B24-77.171-14.5813.4341.0039.60O

Atom 8413 OE2 GLU B24-77.221-16.7252.8841.0039.51O

Atom 8414C GLU B24-78.730-11.809-. 5591.0038.11C

Atom 8415O GLU B24-79.840-11.453-. 9721.0038.20O

Atom 8417N SER B25-77.825-10.941-. 0891.0038.70N

Atom 8418 CA SER B25-78.192-9.560.3121.0039.21C

Atom 8420 CB SER B25-76.995-8.783.9161.0039.29C

Atom 8423 OG SER B25-76.267-8.037-. 0561.0039.40O

Atom 8425C SER B25-78.853-8.738-. 8021.0039.69C

Atom 8426O SER B25-78.707-9.050-1.9951.0039.75O

Atom 8428N ILE B26-79.544-7.670-. 3781.0040.21N

Atom 8429 CA ILE B26-80.554-6.962-1.1891.0040.55C

Atom 8431 CB ILE B26-79.925-6.082-2.3191.0040.66C

Atom 8433 CG1 ILE B26-79.083-4.951-1.7001.0040.73C

Atom 8436 CD1 ILE B26-78.596-3.877-2.6981.0040.68C

Atom 8440 CG2 ILE B26-81.018-5.475-3.2031.0040.88C

Atom 8444C ILE B26-81.575-7.999-1.7141.0040.72C

Atom 8445O ILE B26-81.311-8.710-2.6901.0040.80O

Atom 8447N GLU B27-82.729-8.070-1.0371.0040.86N

Atom 8448 CA GLU B27-83.694-9.190-1.1601.0040.88C

Atom 8450 CB GLU B27-84.782-9.060-. 0611.0040.95C

Atom 8453 CG GLU B27-84.235-9.2571.3791.0041.28C

Atom 8456 CD GLU B27-85.123-8.6572.4841.0041.74C

Atom 8457 OE1 GLU B27-85.593-7.5042.3441.0041.14O

Atom 8458 OE2 GLU B27-85.332-9.3373.5141.0042.36O

Atom 8459C GLU B27-84.290-9.355-2.5871.0040.75C

Atom 8460O GLU B27-83.664-8.936-3.5691.0040.88O

Atom 8462N VAL B28-85.461-9.994-2.7121.0040.40N

Atom 8463 CA VAL B28-86.033-10.361-4.0271.0039.97C

Atom 8465 CB VAL B28-86.034-9.157-5.0531.0040.03C

Atom 8467 CG1 VAL B28-86.494-9.600-6.4441.0039.63C

Atom 8471 CG2 VAL B28-86.900-7.994-4.5251.0039.86C

Atom 8475C VAL B28-85.335-11.600-4.6251.0039.63C

Atom 8476O VAL B28-85.858-12.204-5.5671.0039.63O

Atom 8478N HIS B29-84.175-11.980-4.0691.0039.21N

Atom 8479 CA HIS B29-83.431-13.177-4.5041.0038.81C

Atom 8481 CB HIS B29-81.914-12.913-4.6651.0038.97C

Atom 8484 CG HIS B29-81.571-11.721-5.5121.0039.99C

Atom 8485 ND1 HIS B29-81.181-11.825-6.8341.0040.79N

Atom 8487 CE1 HIS B29-80.931-10.615-7.3121.0040.76C

Atom 8489 NE2 HIS B29-81.134-9.734-6.3461.0040.27N

Atom 8491 CD2 HIS B29-81.525-10.400-5.2091.0040.17C

Atom 8493C HIS B29-83.611-14.340-3.5231.0038.05C

Atom 8494O HIS B29-82.782-15.259-3.5261.0038.02O

Atoms 8496N LYS B30-84.667-14.321-2.6941.0037.06N

Atom 8497 CA LYS B30-85.107-15.559-2.0221.0036.33C

Atom 8499 CB LYS B30-86.056-15.286-. 8361.0036.27C

Atom 8502 CG LYS B30-85.352-14.818.4611.0036.09C

Atom 8505 CD LYS B30-86.355-14.5991.6121.0036.03C

Atom 8508 CE LYS B30-85.811-13.6592.7011.0036.24C

Atom 8511 NZ LYS B30-86.802-13.3563.7891.0035.65N

Atom 8515C LYS B30-85.710-16.510-3.0941.0035.69C

Atom 8516O LYS B30-86.706-17.205-2.8791.0035.35O

Atom 8518N ASP B31-85.075-16.484-4.2681.0035.13N

Atom 8519 CA ASP B31-85.145-17.519-5.2821.0034.64C

Atom 8521 CB ASP B31-84.592-16.962-6.6231.0034.60C

Atom 8524 CG ASP B31-84.419-18.032-7.7251.0034.24C

Atom 8525 OD1 ASP B31-84.914-19.165-7.5701.0034.58O

Atom 8526 OD2 ASP B31-83.776-17.732-8.7611.0031.56O

Atom 8527C ASP B31-84.304-18.675-4.7211.0034.31C

Atom 8528O ASP B31-83.122-18.838-5.0381.0034.03O

Atom 8530N LYS B32-84.917-19.429-3.8131.0033.94N

Atom 8531 CA LYS B32-84.380-20.710-3.3691.0033.36C

Atom 8533 CB LYS B32-83.772-20.607-1.9731.0033.45C

Atom 8536 CG LYS B32-82.540-19.693-1.9511.0033.56C

Atom 8539 CD LYS B32-82.025-19.455-. 5321.0034.17C

Atom 8542 CE LYS B32-81.671-17.987-. 2831.0034.16C

Atom 8545 NZ LYS B32-80.746-17.437-1.3111.0034.07N

Atom 8549C LYS B32-85.490-21.764-3.4991.0032.57C

Atom 8550O LYS B32-85.908-22.412-2.5381.0032.10O

Atom 8552N ALA B33-85.976-21.859-4.7381.0031.66N

Atom 8553 CA ALA B33-86.576-23.055-5.2591.0030.94C

Atom 8555 CB ALA B33-87.247-22.773-6.5971.0030.47C

Atom 8559C ALA B33-85.442-24.081-5.4031.0030.55C

Atom 8560O ALA B33-85.684-25.230-5.7511.0031.12O

Atom 8562N LYS B34-84.200-23.660-5.1611.0029.73N

Atom 8563 CA LYS B34-83.107-24.585-4.8391.0029.09C

Atom 8565 CB LYS B34-81.776-23.817-4.8651.0029.30C

Atom 8568 CG LYS B34-80.678-24.474-5.7261.0029.76C

Atom 8571 CD LYS B34-79.633-23.458-6.2831.0028.74C

Atom 8574 CE LYS B34-78.417-24.186-6.8901.0027.56C

Atom 8577 NZ LYS B34-78.745-25.174-7.9351.0026.16N

Atom 8581C LYS B34-83.376-25.320-3.4721.0028.37C

Atom 8582O LYS B34-83.254-24.755-2.3741.0027.82O

Atom 8584N LYS B35-83.635-26.620-3.6041.0027.53N

Atom 8585 CA LYS B35-84.629-27.429-2.8511.0026.77C

Atom 8587 CB LYS B35-85.729-26.602-2.1701.0026.81C

Atom 8590 CG LYS B35-87.089-26.520-2.9071.0027.05C

Atom 8593 CD LYS B35-88.096-27.604-2.4521.0027.41C

Atom 8596 CE LYS B35-89.394-27.636-3.3001.0027.21C

Atom 8599 NZ LYS B35-90.501-26.792-2.7621.0026.28N

Atom 8603C LYS B35-85.257-28.357-3.9201.0026.03C

Atom 8604O LYS B35-85.853-29.386-3.6261.0026.00O

Atom 8606N LEU B36-85.171-27.909-5.1681.0024.98N

Atom 8607 CA LEU B36-85.095-28.783-6.3191.0024.02C

Atom 8609 CB LEU B36-85.004-27.930-7.5941.0023.83C

Atom 8612 CG LEU B36-86.208-27.103-8.0621.0022.23C

Atom 8614 CD1 LEU B36-85.762-25.873-8.8021.0019.93C

Atom 8618 CD2 LEU B36-87.092-27.930-8.9511.0022.11C

Atom 8622C LEU B36-83.834-29.659-6.1851.0023.58C

Atom 8623O LEU B36-83.840-30.842-6.5081.0023.38O

Atom 8625N GLU B37-82.742-29.046-5.7391.0023.18N

Atom 8626 CA GLU B37-81.510-29.753-5.3961.0022.88C

Atom 8628 CB GLU B37-80.466-28.766-4.8551.0022.76C

Atom 8631 CG GLU B37-79.038-29.297-4.8741.0022.24C

Atom 8634 CD GLU B37-78.085-28.505-4.0091.0021.06C

Atom 8635 OE1 GLU B37-78.368-27.331-3.7371.0019.65O

Atom 8636 OE2 GLU B37-77.037-29.059-3.6151.0020.62O

Atom 8637C GLU B37-81.748-30.856-4.3641.0022.95C

Atom 8638O GLU B37-81.164-31.933-4.4581.0022.99O

Atom 8640N ALA B38-82.591-30.575-3.3721.0023.02N

Atom 8641 CA ALA B38-82.973-31.565-2.3641.0022.93C

Atom 8643 CB ALA B38-83.966-30.959-1.3741.0022.73C

Atom 8647C ALA B38-83.580-32.778-3.0441.0023.05C

Atom 8648O ALA B38-83.170-33.909-2.8131.0022.52O

Atom 8650N GLU B39-84.546-32.506-3.9121.0023.66N

Atom 8651 CA GLU B39-85.273-33.534-4.6421.0024.08C

Atom 8653 CB GLU B39-86.403-32.891-5.4531.0024.28C

Atom 8656 CG GLU B39-87.405-33.869-6.0751.0025.14C

Atom 8659 CD GLU B39-88.773-33.227-6.3411.0026.43C

Atom 8660 OE1 GLU B39-89.232-32.381-5.5191.0025.90O

Atom 8661 OE2 GLU B39-89.387-33.584-7.3751.0026.99O

Atom 8662C GLU B39-84.362-34.359-5.5451.0024.18C

Atom 8663O GLU B39-84.483-35.579-5.5751.0024.32O

Atom 8665N VAL B40-83.450-33.710-6.2691.0024.43N

Atom 8666 CA VAL B40-82.533-34.437-7.1531.0024.59C

Atom 8668 CB VAL B40-81.734-33.496-8.0871.0024.65C

Atom 8670 CG1 VAL B40-80.611-34.258-8.7921.0024.14C

Atom 8674 CG2 VAL B40-82.662-32.852-9.1061.0023.89C

Atom 8678C VAL B40-81.592-35.304-6.3281.0024.99C

Atom 8679O VAL B40-81.265-36.407-6.7171.0024.77O

Atoms 8681N ARG B41-81.184-34.811-5.1711.0025.79N

Atom 8682 CA ARG B41-80.387-35.613-4.2481.0026.75C

Atom 8684 CB ARG B41-80.032-34.823-2.9981.0027.38C

Atom 8687 CG ARG B41-78.568-34.777-2.7571.0030.18C

Atom 8690 CD ARG B41-78.281-34.610-1.2731.0034.43C

Atom 8693 NE ARG B41-76.896-34.198-1.0161.0037.07N

Atom 8695 CZ ARG B41-76.350-33.045-1.4161.0038.54C

Atom 8696 NH1 ARG B41-75.083-32.797-1.1121.0040.04N

Atom 8699 NH2 ARG B41-77.037-32.145-2.1281.0038.45N

Atom 8702C ARG B41-81.081-36.860-3.7621.0026.60C

Atom 8703O ARG B41-80.446-37.894-3.6271.0026.89O

Atom 8705N ARG B42-82.363-36.733-3.4231.0026.41N

Atom 8706 CA ARG B42-83.159-37.870-3.0021.0026.09C

Atom 8708 CB ARG B42-84.588-37.452-2.6741.0025.99C

Atom 8711 CG ARG B42-85.426-38.562-2.0491.0025.45C

Atom 8714 CD ARG B42-86.783-38.078-1.6451.0024.26C

Atom 8717 NE ARG B42-87.549-37.602-2.7941.0023.73N

Atom 8719 CZ ARG B42-88.547-36.722-2.7171.0024.51C

Atom 8720 NH1 ARG B42-88.912-36.195-1.5451.0024.99N

Atom 8723 NH2 ARG B42-89.185-36.354-3.8161.0024.46N

Atom 8726C ARG B42-83.167-38.894-4.1181.0026.28C

Atom 8727O ARG B42-82.864-40.054-3.8881.0026.39O

Atom 8729N GLU B43-83.476-38.460-5.3341.0026.52N

Atom 8730 CA GLU B43-83.476-39.370-6.4791.0027.00C

Atom 8732 CB GLU B43-83.982-38.676-7.7531.0027.50C

Atom 8735 CG GLU B43-85.469-38.275-7.6991.0029.78C

Atom 8738 CD GLU B43-86.342-39.301-6.9741.0032.52C

Atom 8739 OE1 GLU B43-86.388-40.455-7.4451.0035.06O

Atom 8740 OE2 GLU B43-86.966-38.963-5.9361.0033.80O

Atom 8741C GLU B43-82.147-40.059-6.7691.0026.37C

Atom 8742O GLU B43-82.162-41.126-7.3551.0026.63O

Atom 8744N ILE B44-81.018-39.472-6.3731.0025.85N

Atom 8745 CA ILE B44-79.717-40.126-6.5551.0025.55C

Atom 8747 CB ILE B44-78.547-39.121-6.6921.0025.26C

Atom 8749 CG1 ILE B44-78.706-38.273-7.9531.0024.47C

Atom 8752 CD1 ILE B44-77.690-37.163-8.1141.0023.21C

Atom 8756 CG2 ILE B44-77.207-39.863-6.7781.0025.35C

Atom 8760C ILE B44-79.404-41.109-5.4281.0025.84C

Atom 8761O ILE B44-78.925-42.208-5.6981.0025.97O

Atoms 8763N ASN B45-79.663-40.708-4.1771.0026.25N

Atom 8764 CA ASN B45-79.403-41.542-2.9831.0026.34C

Atom 8766 CB ASN B45-79.284-40.681-1.7191.0026.01C

Atom 8769 CG ASN B45-78.072-39.789-1.7231.0024.65C

Atom 8770 OD1 ASN B45-76.957-40.226-1.4341.0022.47O

Atom 8771 ND2 ASN B45-78.288-38.516-2.0091.0023.36N

Atom 8774C ASN B45-80.488-42.586-2.7311.0027.18C

Atom 8775O ASN B45-80.374-43.390-1.8061.0027.30O

Atom 8777N ASN B46-81.553-42.541-3.5271.0028.17N

Atom 8778 CA ASN B46-82.619-43.536-3.4891.0029.02C

Atom 8780 CB ASN B46-83.558-43.289-4.6651.0029.05C

Atom 8783 CG ASN B46-84.615-44.345-4.8061.0028.82C

Atom 8784 OD1 ASN B46-84.861-45.132-3.8951.0028.14O

Atom 8785 ND2 ASN B46-85.255-44.369-5.9681.0029.67N

Atom 8788C ASN B46-82.076-44.958-3.5491.0030.14C

Atom 8789O ASN B46-81.566-45.408-4.5811.0030.30O

Atom 8791N GLU B47-82.218-45.674-2.4461.0031.36N

Atom 8792 CA GLU B47-81.575-46.968-2.2951.0032.61C

Atom 8794 CB GLU B47-81.617-47.430-. 8231.0033.09C

Atom 8797 CG GLU B47-80.974-46.466.2181.0034.19C

Atom 8800 CD GLU B47-81.919-45.337.7211.0034.57C

Atom 8801 OE1 GLU B47-82.911-45.012.0291.0034.53O

Atom 8802 OE2 GLU B47-81.652-44.7621.8051.0034.30O

Atom 8803C GLU B47-82.205-48.046-3.1721.0033.18C

Atom 8804O GLU B47-81.604-49.088-3.3701.0033.44O

Atom 8806N LYS B48-83.408-47.808-3.6921.0034.11N

Atom 8807 CA LYS B48-84.164-48.853-4.3961.0034.85C

Atom 8809 CB LYS B48-85.379-49.254-3.5421.0035.09C

Atom 8812 CG LYS B48-85.003-49.723-2.1271.0036.00C

Atom 8815 CD LYS B48-86.174-50.338-1.3501.0037.13C

Atom 8818 CE LYS B48-87.312-49.340-1.0941.0037.90C

The atom 8821 NZ LYS B48-86.908-48.161-. 2721.0038.31N

Atom 8825C LYS B48-84.586-48.487-5.8351.0035.13C

Atom 8826O LYS B48-85.544-49.030-6.3611.0034.60O

Atom 8828N ALA B49-83.858-47.576-6.4741.0036.09N

Atom 8829 CA ALA B49-84.093-47.261-7.8861.0036.87C

Atom 8831 CB ALA B49-83.550-45.880-8.2381.0036.73C

Atom 8835C ALA B49-83.406-48.325-8.7141.0037.56C

Atom 8836O ALA B49-82.315-48.761-8.3631.0037.62O

Atom 8838N GLU B50-84.028-48.754-9.8071.0038.54N

Atom 8839 CA GLU B50-83.399-49.772-10.6521.0039.40C

Atom 8841 CB GLU B50-84.380-50.384-11.6731.0039.71C

Atom 8844 CG GLU B50-83.959-51.808-12.1791.0041.33C

Atom 8847 CD GLU B50-83.733-52.860-11.0391.0042.88C

Atom 8848 OE1 GLU B50-84.683-53.628-10.7181.0042.94O

Atom 8849 OE2 GLU B50-82.603-52.921-10.4721.0042.96O

Atom 8850C GLU B50-82.171-49.163-11.3301.0039.43C

Atom 8851O GLU B50-82.211-48.017-11.7911.0039.66O

Atom 8853N PHE B51-81.084-49.929-11.3761.0039.32N

Atom 8854 CA PHE B51-79.763-49.360-11.6361.0039.32C

Atom 8856 CB PHE B51-78.675-50.429-11.4761.0039.62C

Atom 8859 CG PHE B51-78.470-50.889-10.0321.0041.82C

Atom 8860 CD1 PHE B51-78.093-49.978-9.0321.0042.93C

Atom 8862 CE1 PHE B51-77.892-50.391-7.7051.0043.30C

Atom 8864 CZ PHE B51-78.059-51.729-7.3591.0044.33C

Atom 8866 CE2 PHE B51-78.430-52.659-8.3411.0044.75C

Atom 8868 CD2 PHE B51-78.633-52.234-9.6771.0044.06C

Atom 8870C PHE B51-79.646-48.625-12.9761.0038.57C

Atom 8871O PHE B51-79.045-47.564-13.0461.0038.50O

Atom 8873N LEU B52-80.262-49.155-14.0241.0037.99N

Atom 8874 CA LEU B52-80.176-48.539-15.3511.0037.42C

Atom 8876 CB LEU B52-80.774-49.476-16.3991.0037.66C

Atom 8879 CG LEU B52-80.502-49.168-17.8761.0038.39C

Atom 8881 CD1 LEU B52-80.171-50.452-18.6521.0038.46C

Atom 8885 CD2 LEU B52-81.703-48.432-18.5001.0039.23C

Atom 8889C LEU B52-80.824-47.143-15.4311.0036.69C

Atom 8890O LEU B52-80.383-46.312-16.2241.0036.59O

Atom 8892N THR B53-81.859-46.879-14.6251.0035.87N

Atom 8893 CA THR B53-82.409-45.510-14.5131.0034.91C

Atom 8895 CB THR B53-83.784-45.421-13.8051.0034.72C

Atom 8897 OG1 THR B53-84.724-46.269-14.4551.0034.04O

Atom 8899 CG2 THR B53-84.316-43.981-13.8551.0034.81C

Atom 8903C THR B53-81.454-44.642-13.7221.0034.05C

Atom 8904O THR B53-81.170-43.513-14.1211.0034.16O

Atoms 8906N LEU B54-80.987-45.167-12.5931.0032.84N

Atom 8907 CA LEU B54-80.027-44.461-11.7721.0032.16C

Atom 8909 CB LEU B54-79.506-45.354-10.6621.0032.27C

Atom 8912 CG LEU B54-78.521-44.702-9.6981.0032.56C

Atom 8914 CD1 LEU B54-79.275-43.760-8.7691.0032.38C

Atom 8918 CD2 LEU B54-77.755-45.789-8.9171.0033.29C

Atoms 8922C LEU B54-78.870-44.006-12.6341.0031.50C

Atom 8923O LEU B54-78.509-42.840-12.6071.0031.98O

Atoms 8925N LEU B55-78.297-44.914-13.4181.0030.43N

Atom 8926 CA LEU B55-77.220-44.540-14.3331.0029.36C

Atom 8928 CB LEU B55-76.765-45.733-15.1731.0029.23C

Atom 8931 CG LEU B55-76.157-46.902-14.3911.0028.60C

Atom 8933 CD1 LEU B55-75.697-48.004-15.3481.0027.60C

Atom 8937 CD2 LEU B55-75.020-46.440-13.4691.0027.20C

Atoms 8941C LEU B55-77.678-43.406-15.2301.0028.60C

Atom 8942O LEU B55-77.063-42.365-15.2671.0028.17O

Atoms 8944N GLU B56-78.786-43.594-15.9191.0028.23N

Atom 8945 CA GLU B56-79.326-42.530-16.7591.0028.64C

Atom 8947 CB GLU B56-80.567-43.031-17.5241.0029.27C

Atom 8950 CG GLU B56-80.229-43.783-18.8291.0031.73C

Atom 8953 CD GLU B56-81.265-44.860-19.2061.0035.52C

Atom 8954 OE1 GLU B56-82.474-44.693-18.8891.0036.97O

Atom 8955 OE2 GLU B56-80.856-45.877-19.8251.0037.55O

Atom 8956C GLU B56-79.632-41.203-15.9951.0027.77C

Atom 8957O GLU B56-79.561-40.103-16.5821.0027.84O

Atoms 8959N LEU B57-79.976-41.303-14.7101.0026.29N

Atom 8960 CA LEU B57-80.158-40.120-13.8951.0025.06C

Atom 8962 CB LEU B57-80.724-40.462-12.5141.0024.83C

Atoms 8965 CG LEU B57-80.952-39.298-11.5441.0023.72C

Atom 8967 CD1 LEU B57-81.909-38.278-12.1171.0021.43C

Atoms 8971 CD2 LEU B57-81.477-39.830-10.2271.0022.41C

Atoms 8975C LEU B57-78.801-39.459-13.7801.0024.40C

Atom 8976O LEU B57-78.591-38.373-14.3061.0024.70O

Atom 8978N ILE B58-77.855-40.133-13.1441.0023.56N

Atom 8979 CA ILE B58-76.509-39.574-12.9911.0022.91C

Atom 8981 CB ILE B58-75.454-40.635-12.5991.0022.49C

Atom 8983 CG1 ILE B58-75.753-41.251-11.2351.0022.09C

Atom 8986 CD1 ILE B58-74.936-42.464-10.9261.0020.88C

Atom 8990 CG2 ILE B58-74.103-39.992-12.5341.0022.63C

Atom 8994C ILE B58-76.062-38.927-14.3021.0022.64C

Atom 8995O ILE B58-75.603-37.796-14.3151.0022.38O

Atom 8997N ASP B59-76.228-39.646-15.4041.0022.56N

Atom 8998 CA ASP B59-75.715-39.196-16.6841.0022.76C

Atom 9000 CB ASP B59-75.926-40.269-17.7571.0022.93C

Atom 9003 CG ASP B59-75.274-39.904-19.0881.0024.58C

Atom 9004 OD1 ASP B59-74.157-39.322-19.0811.0025.70O

Atom 9005 OD2 ASP B59-75.897-40.186-20.1421.0027.51O

Atom 9006C ASP B59-76.343-37.863-17.1041.0022.40C

Atom 9007O ASP B59-75.634-36.939-17.5201.0022.40O

Atom 9009N ASN B60-77.662-37.767-16.9911.0021.91N

Atom 9010 CA ASN B60-78.349-36.500-17.2171.0021.70C

Atom 9012 CB ASN B60-79.867-36.674-17.0881.0022.12C

Atom 9015 CG ASN B60-80.477-37.390-18.2681.0022.76C

Atom 9016 OD1 ASN B60-80.027-37.233-19.3931.0024.28O

Atom 9017 ND2 ASN B60-81.515-38.172-18.0171.0024.36N

Atom 9020C ASN B60-77.898-35.427-16.2341.0021.17C

Atom 9021O ASN B60-77.700-34.273-16.6141.0020.85O

Atom 9023N VAL B61-77.745-35.805-14.9681.0020.60N

Atom 9024 CA VAL B61-77.382-34.841-13.9421.0020.48C

Atom 9026 CB VAL B61-77.277-35.490-12.5511.0020.26C

Atom 9028 CG1 VAL B61-76.585-34.562-11.5651.0019.92C

Atom 9032 CG2 VAL B61-78.668-35.857-12.0491.0020.66C

Atom 9036C VAL B61-76.068-34.208-14.3351.0020.66C

Atom 9037O VAL B61-75.871-32.998-14.1821.0020.74O

Atom 9039N GLN B62-75.187-35.048-14.8751.0020.92N

Atom 9040 CA GLN B62-73.854-34.636-15.2851.0020.69C

Atom 9042 CB GLN B62-72.917-35.847-15.4041.0020.77C

Atom 9045 CG GLN B62-72.456-36.369-14.0351.0020.91C

Atom 9048 CD GLN B62-71.328-37.383-14.1121.0020.75C

Atom 9049 OE1 GLN B62-70.512-37.498-13.1921.0020.93O

Atom 9050 NE2 GLN B62-71.291-38.135-15.1951.0020.39N

Atom 9053C GLN B62-73.900-33.834-16.5671.0020.32C

Atom 9054O GLN B62-73.410-32.712-16.5691.0020.79O

Atom 9056N ARG B63-74.512-34.373-17.6251.0019.87N

Atom 9057 CA ARG B63-74.520-33.696-18.9401.0019.81C

Atom 9059 CB ARG B63-75.240-34.536-20.0131.0019.75C

Atom 9062 CG ARG B63-74.492-35.846-20.3451.0021.69C

Atom 9065 CD ARG B63-75.158-36.786-21.3681.0024.89C

Atom 9068 NE ARG B63-74.674-36.558-22.7411.0029.32N

Atom 9070 CZ ARG B63-75.323-35.878-23.7021.0033.71C

Atom 9071 NH1 ARG B63-76.537-35.345-23.5101.0036.67N

Atom 9074 NH2 ARG B63-74.761-35.736-24.8941.0034.58N

Atom 9077C ARG B63-75.099-32.276-18.8221.0019.39C

Atom 9078O ARG B63-74.553-31.310-19.3951.0019.63O

Atom 9080N LEU B64-76.155-32.148-18.0171.0018.62N

Atom 9081 CA LEU B64-76.811-30.856-17.7531.0017.96C

Atom 9083 CB LEU B64-78.136-31.077-17.0081.0017.97C

Atom 9086 CG LEU B64-79.264-31.737-17.8091.0017.08C

Atom 9088 CD1 LEU B64-80.276-32.354-16.8791.0015.15C

Atom 9092 CD2 LEU B64-79.904-30.734-18.7371.0015.30C

Atom 9096C LEU B64-75.975-29.847-16.9661.0017.39C

Atom 9097O LEU B64-76.370-28.685-16.8251.0017.38O

Atom 9099N GLY B65-74.848-30.286-16.4321.0016.73N

Atom 9100 CA GLY B65-73.917-29.374-15.8181.0016.65C

Atom 9103C GLY B65-74.077-29.249-14.3191.0016.68C

Atom 9104O GLY B65-73.565-28.302-13.7181.0016.79O

Atom 9106N LEU B66-74.758-30.209-13.7021.0016.60N

Atom 9107 CA LEU B66-74.978-30.177-12.2641.0016.58C

Atom 9109 CB LEU B66-76.465-30.389-11.9571.0016.35C

Atom 9112 CG LEU B66-77.363-29.187-12.2341.0015.57C

Atom 9114 CD1 LEU B66-78.828-29.602-12.1631.0015.26C

Atom 9118 CD2 LEU B66-77.063-28.051-11.2701.0013.66C

Atom 9122C LEU B66-74.129-31.203-11.5131.0016.94C

Atom 9123O LEU B66-74.152-31.251-10.2791.0017.50O

Atom 9125N GLY B67-73.373-32.017-12.2361.0017.03N

Atom 9126 CA GLY B67-72.541-33.036-11.6021.0017.13C

Atom 9129C GLY B67-71.642-32.557-10.4611.0017.08C

Atom 9130O GLY B67-71.378-33.317-9.5221.0017.33O

Atom 9132N TYR B68-71.159-31.316-10.5411.0016.83N

Atom 9133 CA TYR B68-70.217-30.804-9.5521.0016.64C

Atom 9135 CB TYR B68-69.654-29.437-9.9511.0016.25C

Atom 9138 CG TYR B68-70.609-28.273-9.8021.0013.51C

Atom 9139 CD1 TYR B68-70.521-27.411-8.7381.0010.49C

Atom 9141 CE1 TYR B68-71.407-26.342-8.6081.0010.25C

Atom 9143 CZ TYR B68-72.382-26.135-9.5551.009.74C

Atom 9144 OH TYR B68-73.253-25.086-9.4501.007.62O

Atom 9146 CE2 TYR B68-72.484-26.978-10.6251.0011.14C

Atom 9148 CD2 TYR B68-71.603-28.037-10.7481.0012.56C

Atom 9150C TYR B68-70.828-30.700-8.1721.0017.79C

Atom 9151O TYR B68-70.107-30.811-7.1821.0018.00O

Atom 9153N ARG B69-72.146-30.485-8.0901.0018.85N

Atom 9154 CA ARG B69-72.784-30.269-6.7891.0019.46C

Atom 9156 CB ARG B69-73.708-29.047-6.8191.0019.23C

Atom 9159 CG ARG B69-75.030-29.219-7.5091.0018.83C

Atom 9162 CD ARG B69-76.053-28.192-6.9851.0017.73C

Atom 9165 NE ARG B69-75.642-26.830-7.2971.0016.01N

Atom 9167 CZ ARG B69-75.330-25.889-6.4171.0014.68C

Atom 9168 NH1 ARG B69-75.400-26.093-5.1121.0014.99N

Atom 9171 NH2 ARG B69-74.959-24.707-6.8611.0015.04N

Atom 9174C ARG B69-73.490-31.489-6.2341.0020.50C

Atom 9175O ARG B69-74.084-31.418-5.1631.0020.67O

Atom 9177N PHE B70-73.416-32.607-6.9591.0022.04N

Atom 9178 CA PHE B70-73.853-33.917-6.4501.0023.03C

Atom 9180 CB PHE B70-75.081-34.428-7.2111.0022.94C

Atom 9183 CG PHE B70-76.236-33.503-7.1571.0021.78C

Atom 9184 CD1 PHE B70-77.024-33.441-6.0281.0020.54C

Atom 9186 CE1 PHE B70-78.076-32.571-5.9591.0020.32C

Atom 9188 CZ PHE B70-78.353-31.752-7.0251.0020.73C

Atom 9190 CE2 PHE B70-77.564-31.796-8.1601.0021.24C

Atom 9192 CD2 PHE B70-76.511-32.665-8.2201.0021.22C

Atom 9194C PHE B70-72.765-34.962-6.5701.0024.33C

Atom 9195O PHE B70-73.069-36.142-6.6141.0024.56O

Atom 9197N GLU B71-71.500-34.547-6.6241.0026.01N

Atom 9198 CA GLU B71-70.413-35.506-6.8041.0027.04C

Atom 9200 CB GLU B71-69.042-34.824-6.8851.0027.48C

Atom 9203 CG GLU B71-67.851-35.816-6.7941.0028.94C

Atom 9206 CD GLU B71-66.491-35.192-7.0811.0030.38C

Atom 9207 OE1 GLU B71-66.398-34.192-7.8351.0030.52O

Atom 9208 OE2 GLU B71-65.501-35.730-6.5441.0032.16O

Atom 9209C GLU B71-70.436-36.531-5.6801.0027.46C

Atom 9210O GLU B71-70.449-37.723-5.9371.0027.67O

Atom 9212N SER B72-70.464-36.087-4.4351.0028.04N

Atom 9213 CA SER B72-70.381-37.044-3.3481.0028.86C

Atom 9215 CB SER B72-70.388-36.340-1.9831.0029.09C

Atom 9218 OG SER B72-71.649-35.751-1.6871.0030.21O

Atom 9220C SER B72-71.519-38.058-3.4811.0029.30C

Atom 9221O SER B72-71.304-39.265-3.3841.0029.24O

Atom 9223N ASP B73-72.719-37.560-3.7561.0030.03N

Atom 9224 CA ASP B73-73.897-38.417-3.8741.0030.63C

Atom 9226 CB ASP B73-75.184-37.598-4.1161.0030.74C

Atom 9229 CG ASP B73-75.419-36.509-3.0521.0031.84C

Atom 9230 OD1 ASP B73-75.562-36.830-1.8411.0031.70O

Atom 9231 OD2 ASP B73-75.473-35.317-3.4431.0033.81O

Atom 9232C ASP B73-73.722-39.443-4.9941.0030.81C

Atom 9233O ASP B73-74.130-40.590-4.8351.0031.39O

Atom 9235N ILE B74-73.122-39.031-6.1121.0030.96N

Atom 9236 CA ILE B74-72.917-39.912-7.2821.0031.04C

Atom 9238 CB ILE B74-72.461-39.114-8.5241.0030.88C

Atom 9240 CG1 ILE B74-73.585-38.213-9.0181.0030.99C

Atom 9243 CD1 ILE B74-73.105-37.120-9.9231.0031.54C

Atom 9247 CG2 ILE B74-72.052-40.035-9.6421.0029.85C

Atom 9251C ILE B74-71.885-41.005-6.9991.0031.45C

Atom 9252O ILE B74-72.098-42.165-7.3471.0031.31O

Atom 9254N ARG B75-70.768-40.628-6.3801.0031.93N

Atom 9255 CA ARG B75-69.778-41.601-5.9471.0032.38C

Atom 9257 CB ARG B75-68.629-40.959-5.1371.0032.87C

Atom 9260 CG ARG B75-67.310-40.751-5.9151.0035.01C

Atom 9263 CD ARG B75-66.089-40.489-5.0031.0037.62C

Atom 9266 NE ARG B75-65.260-41.687-4.7831.0041.03N

Atom 9268 CZ ARG B75-64.461-42.253-5.7001.0044.29C

Atom 9269 NH1 ARG B75-64.385-41.751-6.9311.0046.22N

Atom 9272 NH2 ARG B75-63.741-43.341-5.4041.0044.30N

Atom 9275C ARG B75-70.478-42.673-5.1261.0032.18C

Atom 9276O ARG B75-70.307-43.849-5.3981.0032.19O

Atom 9278N ARG B76-71.280-42.275-4.1431.0032.21N

Atom 9279 CA ARG B76-71.975-43.256-3.3071.0032.61C

Atom 9281 CB ARG B76-72.737-42.582-2.1621.0032.75C

Atom 9284 CG ARG B76-71.880-42.320-. 9291.0033.44C

Atom 9287 CD ARG B76-72.720-42.046.3341.0034.16C

Atom 9290 NE ARG B76-73.797-41.074.1241.0034.53N

Atom 9292 CZ ARG B76-73.627-39.765-. 0631.0034.38C

Atom 9293 NH1 ARG B76-72.414-39.219-0921.0034.34N

Atom 9296 NH2 ARG B76-74.689-38.993-2411.0034.71N

Atom 9299C ARG B76-72.918-44.159-4.1121.0032.81C

Atom 9300O ARG B76-72.863-45.379-3.9951.0032.86O

Atom 9302N ALA B77-73.780-43.559-4.9231.0033.10N

Atom 9303 CA ALA B77-74.655-44.307-5.8131.0033.27C

Atom 9305 CB ALA B77-75.321-43.366-6.7701.0033.26C

Atom 9309C ALA B77-73.884-45.370-6.5781.0033.80C

Atom 9310O ALA B77-74.235-46.542-6.5591.0033.75O

Atom 9312N LEU B78-72.816-44.952-7.2421.0034.77N

Atom 9313 CA LEU B78-71.987-45.868-8.0191.0035.41C

Atom 9315 CB LEU B78-70.845-45.109-8.7021.0035.01C

Atom 9318 CG LEU B78-71.220-44.092-9.7821.0034.37C

Atom 9320 CD1 LEU B78-69.945-43.502-10.3811.0033.93C

Atom 9324 CD2 LEU B78-72.109-44.692-10.8731.0032.94C

Atom 9328C LEU B78-71.409-46.974-7.1421.0036.50C

Atom 9329O LEU B78-71.336-48.124-7.5521.0036.87O

Atom 9331N ASP B79-71.005-46.619-5.9311.0037.74N

Atom 9332 CA ASP B79-70.308-47.545-5.0561.0038.74C

Atom 9334 CB ASP B79-69.787-46.810-3.8191.0038.99C

Atom 9337 CG ASP B79-68.499-47.386-3.3131.0040.08C

Atom 9338 OD1 ASP B79-68.494-48.591-2.9761.0042.32O

Atom 9339 OD2 ASP B79-67.494-46.638-3.2611.0041.24O

Atom 9340C ASP B79-71.207-48.705-4.6451.0039.42C

Atom 9341O ASP B79-70.736-49.835-4.5051.0039.58O

Atom 9343N ARG B80-72.495-48.424-4.4501.0040.26N

Atom 9344 CA ARG B80-73.471-49.470-4.1431.0040.92C

Atom 9346 CB ARG B80-74.823-48.881-3.7161.0041.46C

Atom 9349 CG ARG B80-74.871-48.247-2.3081.0042.87C

Atom 9352 CD ARG B80-76.316-47.826-1.9361.0044.62C

Atom 9355 NE ARG B80-76.946-46.968-2.9491.0045.87N

Atom 9357 CZ ARG B80-76.741-45.651-3.0891.0046.82C

Atom 9358 NH1 ARG B80-75.905-44.989-2.2821.0046.27N

Atom 9361 NH2 ARG B80-77.378-44.988-4.0591.0047.22N

Atom 9364C ARG B80-73.667-50.341-5.3711.0040.77C

Atom 9365O ARG B80-73.642-51.563-5.2751.0041.06O

Atom 9367N PHE B81-73.863-49.705-6.5201.0040.56N

Atom 9368 CA PHE B81-73.986-50.418-7.7871.0040.59C

Atom 9370 CB PHE B81-73.984-49.426-8.9561.0040.73C

Atom 9373 CG PHE B81-73.898-50.063-10.3231.0040.84C

Atom 9374 CD1 PHE B81-75.000-50.668-10.8931.0041.39C

Atom 9376 CE1 PHE B81-74.925-51.236-12.1671.0041.67C

Atom 9378 CZ PHE B81-73.741-51.191-12.8771.0041.33C

Atom 9380 CE2 PHE B81-72.638-50.580-12.3261.0041.19C

Atom 9382 CD2 PHE B81-72.720-50.012-11.0571.0041.39C

Atom 9384C PHE B81-72.871-51.441-7.9531.0040.47C

Atom 9385O PHE B81-73.134-52.583-8.3111.0040.85O

Atom 9387N VAL B82-71.633-51.051-7.6831.0040.26N

Atom 9388 CA VAL B82-70.522-51.986-7.8211.0040.24C

Atom 9390 CB VAL B82-69.173-51.386-7.3791.0040.28C

Atom 9392 CG1 VAL B82-68.164-52.493-7.0631.0039.98C

Atom 9396 CG2 VAL B82-68.644-50.462-8.4511.0040.09C

Atom 9400C VAL B82-70.788-53.230-7.0051.0040.16C

Atom 9401O VAL B82-70.880-54.313-7.5591.0040.13O

Atom 9403N SER B83-70.953-53.056-5.6981.0040.26N

Atom 9404 CA SER B83-71.070-54.174-4.7491.0040.43C

Atom 9406 CB SER B83-70.797-53.666-3.3311.0040.54C

Atom 9409 OG SER B83-71.256-52.330-3.1911.0040.89O

Atom 9411C SER B83-72.415-54.912-4.8311.0040.34C

Atom 9412O SER B83-73.137-55.046-3.8451.0039.99O

Atom 9414N SER B84-72.698-55.400-6.0381.0040.57N

Atom 9415 CA SER B84-73.902-56.154-6.4111.0040.63C

Atom 9417 CB SER B84-75.154-55.679-5.6511.0040.56C

Atom 9420 OG SER B84-75.292-54.268-5.6631.0039.82O

Atom 9422C SER B84-74.104-56.026-7.9401.0040.85C

Atom 9423O SER B84-75.104-55.462-8.3951.0041.24O

Atom 9425N GLY B85-73.136-56.524-8.7201.0040.75N

Atom 9426 CA GLY B85-73.201-56.506-10.1911.0040.64C

Atom 9429C GLY B85-73.225-55.120-10.8151.0040.64C

Atom 9430O GLY B85-74.133-54.794-11.5901.0040.32O

Atom 9432N THR B93-74.847-57.360-18.7591.0036.30N

Atom 9433 CA THR B93-75.593-58.129-19.7741.0035.99C

Atom 9435 CB THR B93-76.251-59.379-19.1521.0035.87C

Atom 9437 OG1 THR B93-76.347-60.389-20.1581.0035.64O

Atom 9439 CG2 THR B93-77.646-59.062-18.5481.0034.95C

Atom 9443C THR B93-76.625-57.274-20.5831.0035.90C

Atom 9444O THR B93-77.764-57.688-20.8431.0035.74O

Atom 9446N SER B94-76.175-56.076-20.9631.0035.58N

Atom 9447 CA SER B94-76.874-55.150-21.8661.0034.97C

Atom 9449 CB SER B94-78.074-54.472-21.1901.0035.06C

Atom 9452 OG SER B94-77.702-53.260-20.5411.0034.37O

Atom 9454C SER B94-75.831-54.097-22.2321.0034.39C

Atom 9455O SER B94-75.212-53.518-21.3411.0034.11O

Atom 9457N LEU B95-75.619-53.864-23.5221.0033.77N

Atom 9458 CA LEU B95-74.490-53.045-23.9521.0033.33C

Atom 9460 CB LEU B95-74.373-53.010-25.4751.0033.30C

Atom 9463 CG LEU B95-73.154-52.246-26.0061.0033.27C

Atom 9465 CD1 LEU B95-71.909-52.455-25.1371.0032.89C

Atom 9469 CD2 LEU B95-72.864-52.649-27.4381.0033.19C

Atom 9473C LEU B95-74.551-51.623-23.4131.0033.00C

Atom 9474O LEU B95-73.588-51.151-22.8091.0032.83O

Atom 9476N HIS B96-75.678-50.949-23.6331.0032.64N

Atom 9477 CA HIS B96-75.853-49.576-23.1711.0032.39C

Atom 9479 CB HIS B96-77.246-49.069-23.5271.0032.64C

Atom 9482 CG HIS B96-77.528-47.689-23.0251.0034.16C

Atom 9483 ND1 HIS B96-76.565-46.703-22.9811.0036.21N

Atom 9485 CE1 HIS B96-77.096-45.594-22.4961.0036.92C

Atom 9487 NE2 HIS B96-78.371-45.827-22.2271.0037.06N

Atom 9489 CD2 HIS B96-78.664-47.130-22.5481.0035.43C

Atom 9491C HIS B96-75.612-49.445-21.6651.0031.78C

Atom 9492O HIS B96-74.936-48.523-212151.0031.95O

Atom 9494N GLY B97-76.156-50.372-20.8871.0031.10N

Atom 9495 CA GLY B97-75.907-50.396-19.4461.0030.52C

Atom 9498C GLY B97-74.434-50.532-19.0851.0029.95C

Atom 9499O GLY B97-73.936-49.797-18.2411.0030.21O

Atom 9501N THR B98-73.740-51.470-19.7261.0029.15N

Atom 9502 CA THR B98-72.314-51.690-19.4901.0028.55C

Atom 9504 CB THR B98-71.803-52.955-20.2481.0028.48C

Atom 9506 OG1 THR B98-72.678-54.066-19.9971.0028.41O

Atom 9508 CG2 THR B98-70.405-53.331-19.8161.0027.74C

Atom 9512C THR B98-71.492-50.452-19.8941.0028.31C

Atom 9513O THR B98-70.658-49.979-19.1271.0028.13O

Atom 9515N ALA B99-71.750-49.910-21.0801.0028.04N

Atom 9516 CA ALA B99-70.984-48.758-21.5781.0027.88C

Atom 9518 CB ALA B99-71.387-48.406-23.0141.0027.78C

Atom 9522C ALA B99-71.127-47.538-20.6841.0027.62C

Atom 9523O ALA B99-70.135-46.885-20.3611.0027.84O

Atoms 9525N LEU B100-72.357-47.233-20.2901.0027.20N

Atom 9526 CA LEU B100-72.613-46.088-19.4221.0027.08C

Atom 9528 CB LEU B100-74.122-45.900-19.2301.0026.95C

Atom 9531 CG LEU B100-74.560-44.715-18.3671.0026.27C

Atoms 9533 CD1 LEU B100-73.753-43.478-18.7341.0026.19C

Atoms 9537 CD2 LEU B100-76.052-44.445-18.5041.0025.20C

Atoms 9541C LEU B100-71.928-46.221-18.0461.0027.23C

Atom 9542O LEU B100-71.368-45.243-17.5231.0027.16O

Atom 9544N SER B101-71.980-47.429-17.4721.0027.00N

Atom 9545 CA SER B101-71.475-47.682-16.1171.0026.63C

Atom 9547 CB SER B101-72.039-48.992-15.5681.0026.49C

Atom 9550 OG SER B101-71.758-50.063-16.4421.0026.38O

Atom 9552C SER B101-69.956-47.740-16.0901.0026.47C

Atom 9553O SER B101-69.326-47.324-15.1211.0026.35O

Atom 9555N PHE B102-69.381-48.288-17.1541.0026.29N

Atom 9556 CA PHE B102-67.934-48.332-17.3221.0025.91C

Atom 9558 CB PHE B102-67.588-49.005-18.6521.0025.96C

Atom 9561 CG PHE B102-66.133-49.020-18.9581.0025.81C

Atom 9562 CD1 PHE B102-65.360-50.115-18.6331.0025.96C

Atom 9564 CE1 PHE B102-63.999-50.122-18.9091.0026.94C

Atom 9566 CZ PHE B102-63.403-49.026-19.5191.0026.27C

Atom 9568 CE2 PHE B102-64.174-47.930-19.8481.0026.19C

Atom 9570 CD2 PHE B102-65.531-47.933-19.5731.0026.04C

Atom 9572C PHE B102-67.416-46.911-17.3151.0025.56C

Atom 9573O PHE B102-66.486-46.564-16.5681.0025.37O

Atom 9575N ARG B103-68.050-46.095-18.1521.0025.20N

Atom 9576 CA ARG B103-67.663-44.696-18.3221.0025.09C

Atom 9578 CB ARG B103-68.510-44.026-19.4001.0025.12C

Atom 9581 CG ARG B103-68.194-42.561-19.5721.0025.41C

Atom 9584 CD ARG B103-68.744-42.035-20.8891.0026.68C

Atom 9587 NE ARG B103-70.197-41.843-20.8771.0027.49N

Atom 9589 CZ ARG B103-70.826-40.851-20.2461.0026.56C

Atom 9590 NH1 ARG B103-70.139-39.963-19.5311.0027.11N

Atom 9593 NH2 ARG B103-72.148-40.759-20.3101.0025.20N

Atom 9596C ARG B103-67.785-43.898-17.0331.0024.61C

Atom 9597O ARG B103-66.865-43.168-16.6591.0024.67O

Atoms 9599N LEU B104-68.927-44.013-16.3711.0023.79N

Atom 9600 CA LEU B104-69.125-43.263-15.1481.0023.23C

Atom 9602 CB LEU B104-70.591-43.342-14.6931.0023.01C

Atom 9605 CG LEU B104-71.607-42.620-15.5841.0021.36C

Atom 9607 CD1 LEU B104-73.002-42.860-15.0671.0019.31C

Atoms 9611 CD2 LEU B104-71.310-41.157-15.6331.0019.57C

Atoms 9615C LEU B104-68.156-43.781-14.0711.0023.15C

Atom 9616O LEU B104-67.445-43.007-13.4231.0023.40O

Atoms 9618N LEU B105-68.106-45.091-13.8941.0022.79N

Atom 9619 CA LEU B105-67.203-45.659-12.9161.0022.40C

Atom 9621 CB LEU B105-67.303-47.178-12.9121.0022.42C

Atom 9624 CG LEU B105-68.505-47.709-12.1631.0021.82C

Atom 9626 CD1 LEU B105-68.810-49.120-12.5911.0021.95C

Atoms 9630 CD2 LEU B105-68.201-47.648-10.6921.0022.14C

Atoms 9634C LEU B105-65.767-45.239-13.1961.0022.33C

Atom 9635O LEU B105-65.049-44.823-12.2751.0022.13O

Atom 9637N ARG B106-65.331-45.342-14.4511.0022.08N

Atom 9638 CA ARG B106-63.953-44.973-14.7301.0022.20C

Atom 9640 CB ARG B106-63.521-45.266-16.1511.0022.33C

Atom 9643 CG ARG B106-62.075-44.827-16.3291.0023.60C

Atom 9646 CD ARG B106-61.383-45.445-17.5131.0024.71C

Atom 9649 NE ARG B106-61.078-46.852-17.3191.0024.66N

Atom 9651 CZ ARG B106-60.418-47.582-18.2061.0025.75C

Atoms 9652 NH1 ARG B106-59.995-47.028-19.3371.0026.41N

Atoms 9655 NH2 ARG B106-60.182-48.866-17.9711.0026.54N

Atoms 9658C ARG B106-63.732-43.504-14.4381.0021.75C

Atom 9659O ARG B106-62.801-43.145-13.7251.0021.50O

Atoms 9661N GLN B107-64.609-42.680-15.0031.0021.69N

Atom 9662 CA GLN B107-64.630-41.239-14.7941.0021.64C

Atom 9664 CB GLN B107-65.964-40.664-15.2611.0021.71C

Atom 9667 CG GLN B107-66.169-39.178-14.9291.0021.97C

Atom 9670 CD GLN B107-67.588-38.723-15.1721.0021.54C

Atom 9671 OE1 GLN B107-68.355-39.365-15.9061.0020.08O

Atom 9672 NE2 GLN B107-67.948-37.600-14.5561.0021.45N

Atom 9675C GLN B107-64.454-40.850-13.3521.0021.70C

Atom 9676O GLN B107-63.776-39.865-13.0781.0022.14O

Atoms 9678N HIS B108-65.091-41.599-12.4501.0021.53N

Atom 9679 CA HIS B108-65.049-41.326-11.0191.0021.63C

Atom 9681 CB HIS B108-66.447-41.535-10.4291.0021.47C

Atom 9684 CG HIS B108-67.416-40.445-10.7521.0020.91C

Atom 9685 ND1 HIS B108-67.541-39.315-9.9761.0020.66N

Atom 9687 CE1 HIS B108-68.476-38.535-10.4901.0020.90C

Atom 9689 NE2 HIS B108-68.966-39.118-11.5671.0019.67N

Atom 9691 CD2 HIS B108-68.326-40.320-11.7471.0020.76C

Atom 9693C HIS B108-64.024-42.209-10.2691.0022.22C

Atom 9694O HIS B108-64.220-42.553-9.1041.0022.17O

Atoms 9696N GLY B109-62.950-42.613-10.9331.0022.91N

Atom 9697 CA GLY B109-61.846-43.288-10.2451.0023.85C

Atom 9700C GLY B109-61.986-44.748-9.8001.0024.50C

Atom 9701O GLY B109-61.053-45.306-9.1891.0024.12O

Atom 9703N PHE B110-63.128-45.371-10.0941.0025.16N

Atom 9704 CA PHE B110-63.309-46.791-9.8001.0025.67C

Atom 9706 CB PHE B110-64.782-47.187-9.8911.0025.80C

Atom 9709 CG PHE B110-65.625-46.656-8.7721.0026.12C

Atom 9710 CD1 PHE B110-65.564-47.230-7.5101.0027.13C

Atom 9712 CE1 PHE B110-66.353-46.751-6.4681.0027.42C

Atom 9714 CZ PHE B110-67.215-45.691-6.6921.0026.93C

Atom 9716 CE2 PHE B110-67.284-45.119-7.9541.0026.49C

Atom 9718 CD2 PHE B110-66.494-45.601-8.9811.0025.96C

Atom 9720C PHE B110-62.505-47.615-10.7931.0025.92C

Atom 9721O PHE B110-62.232-47.157-11.8981.0026.41O

Atom 9723N GLU B111-62.134-48.832-10.4061.0026.06N

Atom 9724 CA GLU B111-61.403-49.724-11.3041.0026.17C

Atom 9726 CB GLU B111-60.444-50.609-10.5111.0026.50C

Atom 9729 CG GLU B111-59.372-51.272-11.3741.0028.11C

Atom 9732 CD GLU B111-58.607-52.377-10.6461.0030.70C

Atom 9733 OE1 GLU B111-58.660-52.436-9.3901.0031.99O

Atom 9734 OE2 GLU B111-57.948-53.190-11.3381.0032.09O

Atom 9735C GLU B111-62.355-50.598-12.1301.0025.60C

Atom 9736O GLU B111-63.116-51.388-11.5851.0025.48O

Atom 9738N VAL B112-62.314-50.439-13.4471.0025.24N

Atom 9739 CA VAL B112-63.026-51.331-14.3571.0024.90C

Atom 9741 CB VAL B112-64.308-50.712-14.9081.0024.92C

Atom 9743 CG1 VAL B112-65.268-50.437-13.7711.0025.26C

Atom 9747 CG2 VAL B112-63.999-49.450-15.7061.0024.77C

Atom 9751C VAL B112-62.144-51.701-15.5221.0024.66C

Atom 9752O VAL B112-61.217-50.964-15.8621.0023.80O

Atom 9754N SER B113-62.467-52.842-16.1321.0024.88N

Atom 9755 CA SER B113-61.604-53.494-17.1091.0025.21C

Atom 9757 CB SER B113-61.286-54.913-16.6541.0024.94C

Atom 9760 OG SER B113-60.357-55.523-17.5281.0024.31O

Atom 9762C SER B113-62.233-53.532-18.4921.0025.88C

Atom 9763O SER B113-63.446-53.651-18.6301.0025.86O

Atom 9765N GLN B114-61.406-53.438-19.5261.0026.92N

Atom 9766 CA GLN B114-61.928-53.491-20.8801.0027.83C

Atom 9768 CB GLN B114-60.846-53.194-21.9171.0027.75C

Atom 9771 CG GLN B114-59.559-53.952-21.7261.0028.05C

Atom 9774 CD GLN B114-58.739-54.077-23.0071.0028.39C

Atom 9775 OE1 GLN B114-59.086-53.515-24.0511.0029.05O

Atom 9776 NE2 GLN B114-57.637-54.808-22.9251.0027.62N

Atom 9779C GLN B114-62.615-54.827-21.1581.0028.78C

Atom 9780O GLN B114-63.484-54.905-22.0221.0029.10O

Atom 9782N GLU B115-62.248-55.861-20.4011.0029.99N

Atom 9783 CA GLU B115-62.888-57.181-20.5051.0030.89C

Atom 9785 CB GLU B115-62.252-58.202-19.5491.0031.10C

Atom 9788 CG GLU B115-60.740-58.394-19.6971.0032.35C

Atom 9791 CD GLU B115-60.320-58.796-21.1061.0034.20C

Atom 9792 OE1 GLU B115-60.965-59.699-21.6881.0034.94O

Atom 9793 OE2 GLU B115-59.348-58.201-21.6341.0035.60O

Atom 9794C GLU B115-64.380-57.120-20.2241.0031.26C

Atom 9795O GLU B115-65.125-57.971-20.6911.0031.54O

Atom 9797N ALA B116-64.825-56.127-19.4651.0031.91N

Atom 9798 CA ALA B116-66.255-55.937-19.2591.0032.69C

Atom 9800 CB ALA B116-66.521-54.648-18.5131.0032.62C

Atom 9804C ALA B116-66.999-55.950-20.5971.0033.33C

Atom 9805O ALA B116-68.156-56.364-20.6681.0033.26O

Atom 9807N PHE B117-66.316-55.521-21.6551.0034.16N

Atom 9808 CA PHE B117-66.889-55.498-22.9961.0034.98C

Atom 9810 CB PHE B117-66.310-54.314-23.7661.0035.02C

Atom 9813 CG PHE B117-66.868-52.997-23.3451.0035.06C

Atom 9814 CD1 PHE B117-66.061-52.046-22.7291.0035.33C

Atom 9816 CE1 PHE B117-66.576-50.825-22.3421.0035.16C

Atom 9818 CZ PHE B117-67.907-50.544-22.5701.0035.37C

Atom 9820 CE2 PHE B117-68.723-51.488-23.1871.0035.28C

Atom 9822 CD2 PHE B117-68.201-52.701-23.5711.0034.68C

Atom 9824C PHE B117-66.676-56.766-23.8301.0035.86C

Atom 9825O PHE B117-66.934-56.755-25.0371.0035.91O

Atom 9827N SER B118-66.215-57.853-23.2121.0036.98N

Atom 9828 CA SER B118-65.924-59.086-23.9601.0037.76C

Atom 9830 CB SER B118-64.836-59.907-23.2621.0037.73C

Atom 9833 OG SER B118-65.272-60.346-21.9871.0037.77O

Atom 9835C SER B118-67.178-59.939-24.2151.0038.48C

Atom 9836O SER B118-67.207-60.724-25.1571.0038.42O

Atom 9838N GLY B119-68.221-59.765-23.4071.0039.51N

Atom 9839 CA GLY B119-69.481-60.473-23.6291.0040.51C

Atom 9842C GLY B119-70.287-60.034-24.8481.0041.51C

Atom 9843O GLY B119-71.444-60.433-25.0021.0041.53O

Atom 9845N PHE B120-69.688-59.210-25.7091.0042.79N

Atom 9846 CA PHE B120-70.382-58.621-26.8641.0043.81C

Atom 9848 CB PHE B120-70.643-57.121-26.6011.0043.76C

Atom 9851 CG PHE B120-71.367-56.853-25.2931.0043.65C

Atom 9852 CD1 PHE B120-72.762-56.874-25.2301.0043.48C

Atom 9854 CE1 PHE B120-73.437-56.650-24.0231.0043.03C

Atom 9856 CZ PHE B120-72.717-56.413-22.8651.0043.09C

Atom 9858 CE2 PHE B120-71.323-56.397-22.9091.0043.38C

Atom 9860 CD2 PHE B120-70.655-56.619-24.1201.0043.41C

Atom 9862C PHE B120-69.607-58.832-28.1751.0044.81C

Atom 9863O PHE B120-69.930-58.238-29.2051.0044.65O

Atom 9865N LYS B121-68.602-59.705-28.1261.0046.19N

Atom 9866 CA LYS B121-67.757-60.004-29.2721.0047.31C

Atom 9868 CB LYS B121-66.275-59.928-28.8701.0047.47C

Atom 9871 CG LYS B121-65.743-58.495-28.6371.0048.13C

Atom 9874 CD LYS B121-64.532-58.439-27.6751.0048.89C

Atom 9877 CE LYS B121-63.261-59.094-28.2411.0049.20C

Atom 9880 NZ LYS B121-62.541-58.232-29.2181.0049.04N

Atom 9884C LYS B121-68.096-61.400-29.8101.0048.15C

Atom 9885O LYS B121-68.199-62.361-29.0431.0048.36O

Atom 9887N ASP B122-68.270-61.510-31.1261.0049.04N

Atom 9888 CA ASP B122-68.611-62.788-31.7541.0049.60C

Atom 9890 CB ASP B122-69.070-62.596-33.2171.0049.52C

Atom 9893 CG ASP B122-67.989-62.015-34.1261.0049.18C

Atom 9894 OD1 ASP B122-66.792-62.306-33.9381.0048.96O

Atom 9895 OD2 ASP B122-68.351-61.268-35.0571.0048.82O

Atom 9896C ASP B122-67.455-63.785-31.6511.0050.31C

Atom 9897O ASP B122-66.369-63.441-31.1711.0050.33O

Atom 9899N GLN B123-67.705-65.014-32.0981.0051.05N

Atom 9900 CA GLN B123-66.716-66.095-32.0571.0051.61C

Atom 9902 CB GLN B123-67.263-67.330-32.7851.0051.82C

Atom 9905 CG GLN B123-68.483-67.986-32.1171.0052.32C

Atom 9908 CD GLN B123-68.117-69.137-31.1841.0052.64C

Atom 9909 OE1 GLN B123-67.146-69.062-30.4321.0053.02O

Atom 9910 NE2 GLN B123-68.904-70.207-31.2301.0052.04N

Atom 9913C GLN B123-65.358-65.694-32.6591.0051.78C

Atom 9914O GLN B123-64.309-66.000-32.0901.0051.67O

Atom 9916N ASN B124-65.388-65.004-33.7991.0052.05N

Atom 9917 CA ASN B124-64.166-64.547-34.4731.0052.25C

Atom 9919 CB ASN B124-64.486-64.042-35.8841.0052.25C

Atom 9922 CG ASN B124-64.911-65.158-36.8191.0051.88C

Atom 9923 OD1 ASN B124-65.918-65.825-36.5921.0051.43O

Atom 9924 ND2 ASN B124-64.144-65.364-37.8801.0051.23N

Atom 9927C ASN B124-63.382-63.466-33.7161.0052.43C

Atom 9928O ASN B124-62.189-63.287-33.9591.0052.33O

Atom 9930N GLY B125-64.051-62.747-32.8151.0052.66N

Atom 9931 CA GLY B125-63.396-61.745-31.9681.0052.68C

Atom 9934C GLY B125-63.916-60.329-32.1351.0052.63C

Atom 9935O GLY B125-63.539-59.447-31.3671.0052.57O

Atom 9937N ASN B126-64.782-60.117-33.1291.0052.54N

Atom 9938 CA ASN B126-65.343-58.793-33.4431.0052.41C

Atom 9940 CB ASN B126-65.575-58.671-34.9491.0052.40C

Atom 9943 CG ASN B126-64.322-58.951-35.7511.0052.64C

Atom 9944 OD1 ASN B126-63.426-59.665-35.2971.0052.77O

Atom 9945 ND2 ASN B126-64.249-58.390-36.9521.0053.00N

Atom 9948C ASN B126-66.656-58.524-32.7121.0052.10C

Atom 9949O ASN B126-67.253-59.432-32.1531.0052.27O

Atom 9951N PHE B127-67.111-57.279-32.7241.0051.61N

Atom 9952 CA PHE B127-68.362-56.936-32.0551.0051.23C

Atom 9954 CB PHE B127-68.506-55.416-31.9051.0051.21C

Atom 9957 CG PHE B127-67.702-54.848-30.7701.0050.58C

Atom 9958 CD1 PHE B127-66.513-54.192-31.0031.0050.15C

Atom 9960 CE1 PHE B127-65.777-53.686-29.9481.0050.15C

Atom 9962 CZ PHE B127-66.225-53.839-28.6471.0049.71C

Atom 9964 CE2 PHE B127-67.399-54.496-28.4051.0049.50C

Atom 9966 CD2 PHE B127-68.132-54.999-29.4591.0049.99C

Atom 9968C PHE B127-69.537-57.505-32.8211.0050.99C

Atom 9969O PHE B127-69.468-57.641-34.0401.0050.92O

Atom 9971N LEU B128-70.609-57.840-32.1061.0050.83N

Atom 9972 CA LEU B128-71.799-58.422-32.7311.0050.76C

Atom 9974 CB LEU B128-72.780-58.953-31.6691.0050.80C

Atom 9977 CG LEU B128-72.341-60.098-30.7341.0050.91C

Atom 9979 CD1 LEU B128-73.483-60.532-29.8131.0050.61C

Atom 9983 CD2 LEU B128-71.818-61.303-31.4971.0050.79C

Atom 9987C LEU B128-72.500-57.407-33.6461.0050.55C

Atom 9988O LEU B128-73.105-56.455-33.1711.0050.34O

Atom 9990N GLU B129-72.402-57.628-34.9571.0050.50N

Atom 9991 CA GLU B129-73.038-56.783-35.9821.0050.48C

Atom 9993 CB GLU B129-73.150-57.551-37.3101.0050.68C

Atom 9996 CG GLU B129-72.262-57.024-38.4341.0051.36C

Atom 9999 CD GLU B129-72.799-55.745-39.0601.0051.88C

Atom 10000 OE1 GLU B129-72.110-54.707-38.9611.0052.72O

Atom 10001 OE2 GLU B129-73.906-55.773-39.6431.0051.58O

Atom 10002C GLU B129-74.428-56.264-35.6291.0050.25C

Atom 10003O GLU B129-74.737-55.110-35.8991.0050.18O

Atom 10005N ASN B130-75.263-57.125-35.0471.0050.06N

Atom 10006 CA ASN B130-76.678-56.806-34.7851.0049.71C

Atom 10008 CB ASN B130-77.477-58.100-34.5501.0049.69C

Atom 10011 CG ASN B130-77.053-58.837-33.2911.0049.39C

Atom 10012 OD1 ASN B130-76.357-59.848-33.3611.0048.74O

Atom 10013 ND2 ASN B130-77.468-58.329-32.1341.0048.99N

Atom 10016C ASN B130-76.934-55.800-33.6461.0049.37C

Atom 10017O ASN B130-78.083-55.456-33.3661.0049.29O

Atom 10019N LEU B131-75.868-55.336-32.9961.0048.98N

Atom 10020 CA LEU B131-75.957-54.279-31.9881.0048.56C

Atom 10022 CB LEU B131-74.797-54.392-30.9911.0048.44C

Atom 10025 CG LEU B131-74.759-55.671-30.1481.0048.19C

Atom 10027 CD1 LEU B131-73.382-55.852-29.5231.0047.23C

Atom 10031 CD2 LEU B131-75.861-55.670-29.0831.0047.77C

Atom 10035C LEU B131-75.968-52.875-32.6041.0048.29C

Atom 10036O LEU B131-76.022-51.895-31.8741.0048.44O

Atom 10038N LYS B132-75.927-52.771-33.9341.0047.95N

Atom 10039 CA LYS B132-76.020-51.471-34.6211.0047.64C

Atom 10041 CB LYS B132-75.548-51.590-36.0801.0047.63C

Atom 10044 CG LYS B132-76.595-52.235-36.9981.0048.19C

Atom 10047 CD LYS B132-76.111-52.483-38.4291.0048.16C

Atom 10050 CE LYS B132-77.239-53.040-39.2901.0047.23C

Atom 10053 NZ LYS B132-76.725-53.936-40.3311.0047.01N

Atom 10057C LYS B132-77.449-50.907-34.5971.0047.13C

Atom 10058O LYS B132-77.683-49.772-35.0051.0046.87O

Atom 10060N GLU B133-78.403-51.716-34.1491.0046.77N

Atom 10061 CA GLU B133-79.806-51.315-34.1071.0046.49C

Atom 10063 CB GLU B133-80.691-52.458-34.6221.0046.56C

Atom 10066 CG GLU B133-80.732-52.515-36.1551.0047.01C

Atom 10069 CD GLU B133-80.737-53.926-36.7151.0047.40C

Atom 10070 OE1 GLU B133-81.500-54.775-36.2061.0047.97O

Atom 10071 OE2 GLU B133-79.983-54.177-37.6791.0047.22O

Atom 10072C GLU B133-80.260-50.830-32.7231.0045.92C

Atom 10073O GLU B133-81.369-50.308-32.6001.0046.14O

Atom 10075N ASP B134-79.424-51.002-31.6911.0044.98N

Atom 10076 CA ASP B134-79.611-50.277-30.4281.0044.14C

Atom 10078 CB ASP B134-79.375-51.162-29.1971.0043.95C

Atom 10081 CG ASP B134-79.646-50.419-27.8831.0043.57C

Atom 10082 OD1 ASP B134-80.014-49.230-27.9191.0042.21O

Atom 10083 OD2 ASP B134-79.488-51.011-26.8021.0043.69O

Atom 10084C ASP B134-78.662-49.073-30.4261.0043.47C

Atom 10085O ASP B134-77.478-49.196-30.1041.0043.55O

Atom 10087N ILE B135-79.198-47.908-30.7761.0042.47N

Atom 10088 CA ILE B135-78.375-46.739-31.0331.0041.65C

Atom 10090 CB ILE B135-79.080-45.783-32.0121.0041.45C

Atom 10092 CG1 ILE B135-78.877-46.313-33.4341.0041.74C

Atom 10095 CD1 ILE B135-79.174-45.331-34.5401.0042.77C

Atom 10099 CG2 ILE B135-78.533-44.391-31.9051.0041.68C

Atom 10103C ILE B135-77.901-46.059-29.7461.0041.14C

Atom 10104O ILE B135-76.752-45.624-29.6761.0041.11O

Atom 10106N LYS B136-78.742-45.998-28.7141.0040.53N

Atom 10107 CA LYS B136-78.281-45.480-27.4091.0040.10C

Atom 10109 CB LYS B136-79.431-45.361-26.3751.0040.40C

Atom 10112 CG LYS B136-79.910-46.697-25.7861.0042.49C

Atom 10115 CD LYS B136-81.002-46.574-24.6981.0044.79C

Atom 10118 CE LYS B136-81.599-47.994-24.3631.0046.03C

Atom 10121 NZ LYS B136-82.231-48.149-22.9941.0046.23N

Atom 10125C LYS B136-77.104-46.327-26.8631.0038.85C

Atom 10126O LYS B136-76.246-45.806-26.1431.0038.91O

Atom 10128N ALA B137-77.062-47.617-27.2191.0037.27N

Atom 10129 CA ALA B137-75.935-48.486-26.8641.0035.88C

Atom 10131 CB ALA B137-76.255-49.952-27.1161.0035.69C

Atom 10135C ALA B137-74.708-48.085-27.6451.0034.63C

Atom 10136O ALA B137-73.647-47.894-27.0551.0034.70O

Atom 10138N ILE B138-74.845-47.946-28.9651.0033.12N

Atom 10139 CA ILE B138-73.693-47.597-29.8051.0031.97C

Atom 10141 CB ILE B138-74.020-47.572-31.2961.0031.50C

Atom 10143 CG1 ILE B138-74.433-48.955-31.7741.0031.28C

Atom 10146 CD1 ILE B138-73.460-50.052-31.4171.0030.86C

Atom 10150 CG2 ILE B138-72.819-47.138-32.0731.0030.61C

Atom 10154C ILE B138-73.124-46.245-29.4131.0031.57C

Atom 10155O ILE B138-71.909-46.090-29.3051.0031.77O

Atom 10157N LEU B139-73.997-45.268-29.1921.0030.92N

Atom 10158 CA LEU B139-73.555-43.962-28.7131.0030.29C

Atom 10160 CB LEU B139-74.732-43.000-28.5301.0030.13C

Atom 10163 CG LEU B139-74.778-41.890-29.5741.0029.96C

Atom 10165 CD1 LEU B139-73.496-41.060-29.5081.0028.26C

Atoms 10169 CD2 LEU B139-76.022-41.019-29.3971.0029.48C

Atom 10173C LEU B139-72.835-44.136-27.3971.0029.95C

Atom 10174O LEU B139-71.709-43.687-27.2321.0030.45O

Atom 10176N SER B140-73.492-44.807-26.4631.0029.33N

Atom 10177 CA SER B140-72.916-45.061-25.1501.0028.84C

Atom 10179 CB SER B140-73.900-45.878-24.2981.0028.93C

Atom 10182 OG SER B140-73.527-45.870-22.9301.0030.33O

Atom 10184C SER B140-71.555-45.770-25.2431.0027.78C

Atom 10185O SER B140-70.637-45.454-24.4891.0027.46O

Atom 10187N LEU B141-71.432-46.719-26.1671.0026.82N

Atom 10188 CA LEU B141-70.178-47.433-26.3481.0026.34C

Atom 10190 CB LEU B141-70.366-48.658-27.2561.0026.16C

Atom 10193 CG LEU B141-69.098-49.472-27.5841.0026.09C

Atom 10195 CD1 LEU B141-68.355-49.960-26.3301.0024.64C

Atom 10199 CD2 LEU B141-69.455-50.643-28.4811.0025.94C

Atoms 10203C LEU B141-69.124-46.476-26.9141.0025.89C

Atom 10204O LEU B141-68.025-46.346-26.3661.0025.77O

Atom 10206N TYR B142-69.471-45.809-28.0081.0025.41N

Atom 10207 CA TYR B142-68.609-44.804-28.6101.0025.03C

Atom 10209 CB TYR B142-69.399-43.982-29.6171.0024.80C

Atom 10212 CG TYR B142-68.736-42.695-30.0431.0024.47C

Atom 10213 CD1 TYR B142-67.761-42.686-31.0291.0024.18C

Atom 10215 CE1 TYR B142-67.166-41.516-31.4381.0024.70C

Atom 10217 CZ TYR B142-67.548-40.315-30.8711.0025.80C

Atom 10218 OH TYR B142-66.940-39.129-31.2791.0027.63O

Atom 10220 CE2 TYR B142-68.522-40.299-29.8901.0025.57C

Atom 10222 CD2 TYR B142-69.110-41.485-29.4851.0024.73C

Atom 10224C TYR B142-68.095-43.883-27.5371.0025.17C

Atom 10225O TYR B142-66.886-43.732-27.3601.0025.40O

Atom 10227N GLU B143-69.038-43.293-26.8071.0025.12N

Atom 10228 CA GLU B143-68.744-42.256-25.8281.0025.10C

Atom 10230 CB GLU B143-70.046-41.726-25.2261.0025.33C

Atom 10233 CG GLU B143-70.006-40.244-24.8491.0027.57C

Atom 10236 CD GLU B143-70.321-39.313-26.0231.0030.43C

Atom 10237 OE1 GLU B143-69.343-38.764-26.5831.0032.89O

Atom 10238 OE2 GLU B143-71.526-39.130-26.3771.0030.86O

Atoms 10239C GLU B143-67.794-42.746-24.7291.0024.43C

Atom 10240O GLU B143-67.026-41.959-24.1791.0024.06O

Atom 10242N ALA B144-67.840-44.050-24.4491.0024.01N

Atom 10243 CA ALA B144-67.033-44.681-23.3991.0023.74C

Atom 10245 CB ALA B144-67.726-45.943-22.8831.0023.48C

Atom 10249C ALA B144-65.631-45.025-23.8641.0023.57C

Atom 10250O ALA B144-64.720-45.171-23.0601.0023.69O

Atom 10252N SER B145-65.455-45.168-25.1651.0023.45N

Atom 10253 CA SER B145-64.168-45.568-25.7011.0023.44C

Atom 10255 CB SER B145-64.300-45.856-27.2141.0023.63C

Atom 10258 OG SER B145-64.822-44.748-27.9521.0024.24O

Atom 10260C SER B145-63.065-44.520-25.4161.0023.24C

Atom 10261O SER B145-61.877-44.848-25.2881.0023.25O

Atom 10263N PHE B146-63.454-43.257-25.2851.0022.92N

Atom 10264 CA PHE B146-62.464-42.189-25.1701.0022.35C

Atom 10266 CB PHE B146-63.090-40.837-25.4781.0022.09C

Atom 10269 CG PHE B146-63.505-40.717-26.9111.0022.40C

Atom 10270 CD1 PHE B146-62.619-40.229-27.8681.0021.98C

Atom 10272 CE1 PHE B146-62.985-40.156-29.2011.0021.80C

Atom 10274 CZ PHE B146-64.241-40.579-29.5941.0021.91C

Atom 10276 CE2 PHE B146-65.123-41.098-28.6491.0022.29C

Atom 10278 CD2 PHE B146-64.751-41.170-27.3231.0022.34C

Atom 10280C PHE B146-61.762-42.208-23.8371.0021.91C

Atom 10281O PHE B146-60.669-41.683-23.7331.0022.30O

Atom 10283N LEU B147-62.361-42.864-22.8411.0021.27N

Atom 10284 CA LEU B147-61.727-43.050-21.5351.0020.49C

Atom 10286 CB LEU B147-62.791-43.333-20.4781.0020.14C

Atom 10289 CG LEU B147-63.609-42.109-20.1021.0018.87C

Atom 10291 CD1 LEU B147-64.813-42.020-20.9591.0015.94C

Atom 10295 CD2 LEU B147-63.988-42.189-18.6421.0018.62C

Atom 10299C LEU B147-60.678-44.163-21.4981.0020.41C

Atom 10300O LEU B147-60.243-44.552-20.4151.0020.44O

Atom 10302N ALA B148-60.268-44.664-22.6621.0020.28N

Atom 10303 CA ALA B148-59.330-45.784-22.7451.0020.33C

Atom 10305 CB ALA B148-59.188-46.231-24.1941.0020.15C

Atom 10309C ALA B148-57.952-45.462-22.1701.0020.54C

Atomic 10310O ALA B148-57.435-44.366-22.3411.0020.23O

Atom 10312N LEU B149-57.366-46.435-21.4861.0021.19N

Atom 10313 CA LEU B149-55.969-46.354-21.0671.0022.02C

Atom 10315 CB LEU B149-55.768-47.073-19.7251.0021.90C

Atom 10318 CG LEU B149-56.541-46.496-18.5231.0021.50C

Atom 10320 CD1 LEU B149-55.979-47.006-17.2231.0020.96C

Atoms 10324 CD2 LEU B149-56.520-44.974-18.5051.0020.95C

Atoms 10328C LEU B149-55.054-46.930-22.1591.0022.84C

Atom 10329O LEU B149-55.507-47.678-23.0171.0022.91O

Atoms 10331N GLU B150-53.781-46.550-22.1631.0023.93N

Atom 10332 CA GLU B150-52.858-47.071-23.1741.0025.03C

Atom 10334 CB GLU B150-51.472-46.431-23.0121.0025.41C

Atom 10337 CG GLU B150-50.530-46.608-24.2131.0027.44C

Atom 10340 CD GLU B150-49.132-45.987-23.9921.0030.04C

Atoms 10341 OE1 GLU B150-48.925-45.330-22.9431.0031.41O

Atoms 10342 OE2 GLU B150-48.242-46.161-24.8671.0030.34O

Atoms 10343C GLU B150-52.787-48.600-23.0241.0025.36C

Atom 10344O GLU B150-52.613-49.098-21.9111.0025.58O

Atoms 10346N GLY B151-52.968-49.337-24.1221.0025.79N

Atom 10347 CA GLY B151-52.959-50.816-24.0861.0026.11C

Atom 10350C GLY B151-54.323-51.522-24.0471.0026.44C

Atom 10351O GLY B151-54.393-52.747-24.1351.0026.91O

Atom 10353N GLU B152-55.407-50.768-23.8991.0026.58N

Atom 10354 CA GLU B152-56.757-51.319-23.9711.0026.57C

Atom 10356 CB GLU B152-57.697-50.531-23.0651.0026.74C

Atom 10359 CG GLU B152-57.291-50.595-21.5961.0027.63C

Atom 10362 CD GLU B152-58.271-49.893-20.6681.0028.86C

Atom 10363 OE1 GLU B152-58.239-50.192-19.4491.0028.80O

Atom 10364 OE2 GLU B152-59.066-49.044-21.1541.0029.26O

Atom 10365C GLU B152-57.254-51.303-25.4151.0026.53C

Atom 10366O GLU B152-57.937-50.381-25.8691.0026.00O

Atomic 10368N ASN B153-56.888-52.354-26.1271.0026.77N

Atom 10369 CA ASN B153-57.189-52.498-27.5451.0027.05C

Atom 10371 CB ASN B153-56.345-53.640-28.1041.0027.12C

Atom 10374 CG ASN B153-56.770-54.992-27.5491.0027.81C

Atom 10375 OD1 ASN B153-56.540-55.307-26.3791.0027.65O

Atoms 10376 ND2 ASN B153-57.426-55.782-28.3821.0029.43N

Atoms 10379C ASN B153-58.659-52.788-27.8731.0027.09C

Atom 10380O ASN B153-59.053-52.658-29.0291.0027.11O

Atom 10382N ILE B154-59.448-53.223-26.8841.0027.17N

Atom 10383 CA ILE B154-60.865-53.544-27.1001.0027.11C

Atom 10385 CB ILE B154-61.454-54.369-25.9561.0026.99C

Atom 10387 CG1 ILE B154-60.811-55.750-25.9071.0027.16C

Atom 10390 CD1 ILE B154-61.309-56.622-24.7461.0027.41C

Atom 10394 CG2 ILE B154-62.953-54.519-26.1241.0026.65C

Atom 10398C ILE B154-61.704-52.284-27.2291.0027.43C

Atom 10399O ILE B154-62.718-52.279-27.9391.0027.39O

Atom 10401N LEU B155-61.296-51.226-26.5221.0027.76N

Atom 10402 CA LEU B155-61.964-49.918-26.6091.0027.75C

Atom 10404 CB LEU B155-61.578-49.024-25.4301.0027.31C

Atom 10407 CG LEU B155-61.968-49.544-24.0521.0026.64C

Atom 10409 CD1 LEU B155-61.444-48.631-22.9811.0025.82C

Atom 10413 CD2 LEU B155-63.465-49.674-23.9441.0026.45C

Atoms 10417C LEU B155-61.620-49.226-27.9241.0028.32C

Atom 10418O LEU B155-62.499-48.672-28.5831.0028.72O

Atom 10420N ASP B156-60.348-49.264-28.3091.0028.84N

Atom 10421 CA ASP B156-59.934-48.737-29.6011.0029.43C

Atom 10423 CB ASP B156-58.423-48.928-29.8231.0029.92C

Atom 10426 CG ASP B156-57.566-47.912-29.0451.0031.35C

Atom 10427 OD1 ASP B156-57.803-46.680-29.1621.0033.23O

Atom 10428 OD2 ASP B156-56.640-48.351-28.3241.0033.08O

Atom 10429C ASP B156-60.719-49.411-30.7171.0029.36C

Atom 10430O ASP B156-61.075-48.768-31.6971.0029.33O

Atom 10432N GLU B157-60.981-50.705-30.5581.0029.63N

Atom 10433 CA GLU B157-61.845-51.457-31.4791.0029.98C

Atom 10435 CB GLU B157-61.729-52.971-31.2341.0030.30C

Atom 10438 CG GLU B157-60.664-53.647-32.0871.0031.79C

Atom 10441 CD GLU B157-60.075-54.901-31.4391.0033.87C

Atom 10442 OE1 GLU B157-60.793-55.560-30.6401.0035.07O

Atom 10443 OE2 GLU B157-58.894-55.223-31.7431.0033.70O

Atom 10444C GLU B157-63.304-51.030-31.3491.0029.53C

Atom 10445O GLU B157-63.999-50.878-32.3511.0029.53O

Atom 10447N ALA B158-63.758-50.853-30.1121.0029.11N

Atom 10448 CA ALA B158-65.104-50.370-29.8401.0028.87C

Atom 10450 CB ALA B158-65.307-50.195-28.3511.0028.82C

Atom 10454C ALA B158-65.383-49.065-30.5671.0028.73C

Atom 10455O ALA B158-66.485-48.857-31.0651.0028.80O

Atom 10457N LYS B159-64.385-48.197-30.6421.0028.65N

Atom 10458 CA LYS B159-64.553-46.910-31.2961.0028.98C

Atom 10460 CB LYS B159-63.439-45.950-30.8571.0029.16C

Atom 10463 CG LYS B159-63.558-44.536-31.4261.0029.82C

Atom 10466 CD LYS B159-62.812-43.493-30.5921.0030.96C

Atom 10469 CE LYS B159-61.295-43.610-30.6911.0031.57C

Atom 10472 NZ LYS B159-60.630-42.426-30.0791.0031.49N

Atom 10476C LYS B159-64.594-47.041-32.8261.0029.08C

Atom 10477O LYS B159-65.385-46.372-33.4861.0028.73O

Atom 10479N VAL B160-63.736-47.891-33.3861.0029.53N

Atom 10480 CA VAL B160-63.686-48.087-34.8361.0029.89C

Atom 10482 CB VAL B160-62.466-48.971-35.2821.0029.93C

Atom 10484 CG1 VAL B160-62.576-49.375-36.7561.0029.58C

Atom 10488 CG2 VAL B160-61.152-48.244-35.0401.0029.41C

Atom 10492C VAL B160-65.001-48.723-35.2631.0030.32C

Atom 10493O VAL B160-65.507-48.459-36.3621.0030.41O

Atom 10495N PHE B161-65.558-49.540-34.3711.0030.83N

Atom 10496 CA PHE B161-66.854-50.178-34.5991.0031.34C

Atom 10498 CB PHE B161-67.090-51.321-33.5991.0031.34C

Atom 10501 CG PHE B161-68.492-51.834-33.6031.0031.09C

Atom 10502 CD1 PHE B161-68.940-52.636-34.6331.0031.61C

Atom 10504 CE1 PHE B161-70.249-53.098-34.6491.0031.48C

Atom 10506 CZ PHE B161-71.114-52.748-33.6281.0030.76C

Atom 10508 CE2 PHE B161-70.677-51.944-32.6061.0030.19C

Atom 10510 CD2 PHE B161-69.378-51.486-32.5971.0030.70C

Atom 10512C PHE B161-67.992-49.173-34.5041.0031.65C

Atom 10513O PHE B161-68.785-49.038-35.4321.0031.62O

Atom 10515N ALA B162-68.068-48.483-33.3731.0032.26N

Atom 10516 CA ALA B162-69.135-47.519-33.1291.0032.84C

Atom 10518 CB ALA B162-68.948-46.854-31.7781.0032.66C

Atom 10522C ALA B162-69.224-46.474-34.2451.0033.40C

Atom 10523O ALA B162-70.229-46.408-34.9371.0033.45O

Atom 10525N ILE B163-68.164-45.697-34.4441.0034.38N

Atom 10526 CA ILE B163-68.166-44.610-35.4391.0035.23C

Atom 10528 CB ILE B163-66.734-44.062-35.7331.0035.18C

Atom 10530 CG1 ILE B163-66.092-43.457-34.4881.0035.21C

Atom 10533 CD1 ILE B163-64.620-43.171-34.6631.0035.96C

Atom 10537 CG2 ILE B163-66.778-42.977-36.7991.0034.72C

Atom 10541C ILE B163-68.778-45.052-36.7661.0036.18C

Atom 10542O ILE B163-69.588-44.335-37.3601.0035.87O

Atom 10544N SER B164-68.379-46.240-37.2171.0037.67N

Atom 10545 CA SER B164-68.761-46.752-38.5391.0038.74C

Atom 10547 CB SER B164-68.104-48.117-38.8151.0038.80C

Atom 10550 OG SER B164-68.733-49.158-38.0771.0039.07O

Atom 10552C SER B164-70.277-46.861-38.6991.0039.51C

Atom 10553O SER B164-70.820-46.494-39.7371.0039.96O

Atom 10555N HIS B165-70.962-47.363-37.6801.0040.28N

Atom 10556 CA HIS B165-72.410-47.485-37.7671.0041.07C

Atom 10558 CB HIS B165-72.911-48.686-36.9571.0041.38C

Atom 10561 CG HIS B165-72.571-50.005-37.5871.0042.65C

Atom 10562 ND1 HIS B165-71.647-50.875-37.0461.0043.54N

Atom 10564 CE1 HIS B165-71.535-51.938-37.8251.0043.54C

Atom 10566 NE2 HIS B165-72.346-51.785-38.8581.0043.25N

Atom 10568 CD2 HIS B165-73.001-50.582-38.7371.0043.31C

Atom 10570C HIS B165-73.125-46.193-37.3801.0041.21C

Atom 10571O HIS B165-74.257-45.980-37.8051.0041.53O

Atom 10573N LEU B166-72.459-45.326-36.6141.0041.32N

Atom 10574 CA LEU B166-73.042-44.039-36.2011.0041.31C

Atom 10576 CB LEU B166-72.317-43.460-34.9731.0041.14C

Atom 10579 CG LEU B166-72.732-43.975-33.5891.0040.03C

Atom 10581 CD1 LEU B166-71.673-43.634-32.5791.0038.86C

Atom 10585 CD2 LEU B166-74.077-43.421-33.1511.0038.52C

Atom 10589C LEU B166-73.045-42.992-37.3131.0041.80C

Atom 10590O LEU B166-74.006-42.230-37.4421.0041.73O

Atom 10592N LYS B167-71.982-42.947-38.1161.0042.47N

Atom 10593 CA LYS B167-71.847-41.891-39.1371.0043.00C

Atom 10595 CB LYS B167-70.416-41.822-39.7021.0043.12C

Atom 10598 CG LYS B167-69.937-43.068-40.4501.0044.12C

Atom 10601 CD LYS B167-69.138-42.725-41.7361.0045.36C

Atom 10604 CE LYS B167-67.898-41.842-41.4831.0045.65C

Atom 10607 NZ LYS B167-67.267-41.400-42.7621.0044.94N

Atom 10611C LYS B167-72.873-41.950-40.2831.0042.99C

Atom 10612O LYS B167-72.826-41.124-41.1821.0042.95O

Atom 10614N GLU B168-73.791-42.912-40.2441.0043.23N

Atom 10615 CA GLU B168-74.928-42.940-41.1671.0043.44C

Atom 10617 CB GLU B168-74.652-43.969-42.2721.0043.58C

Atom 10620 CG GLU B168-73.918-43.363-43.5011.0044.36C

Atom 10623 CD GLU B168-72.618-44.082-43.8951.0044.53C

Atom 10624 OE1 GLU B168-71.853-44.494-42.9921.0044.71O

Atom 10625 OE2 GLU B168-72.351-44.197-45.1151.0043.31O

Atom 10626C GLU B168-76.263-43.214-40.4421.0043.24C

Atom 10627O GLU B168-76.932-42.291-39.9421.0042.54O

Atoms 10629N GLY B175-83.548-42.037-36.2391.0049.43N

Atom 10630 CA GLY B175-84.473-41.266-35.4161.0049.54C

Atom 10633C GLY B175-84.709-39.884-36.0011.0049.76C

Atom 10634O GLY B175-84.828-39.741-37.2201.0049.70O

Atom 10636N LYS B176-84.766-38.870-35.1311.0049.95N

Atom 10637 CA LYS B176-85.014-37.468-35.5341.0050.05C

Atom 10639 CB LYS B176-86.522-37.225-35.7301.0050.27C

Atom 10642 CG LYS B176-87.301-36.813-34.4601.0051.33C

Atom 10645 CD LYS B176-88.553-37.658-34.2021.0052.21C

Atom 10648 CE LYS B176-88.841-37.754-32.6951.0052.36C

Atoms 10651 NZ LYS B176-90.029-38.607-32.4221.0052.15N

Atom 10655C LYS B176-84.427-36.432-34.5541.0049.75C

Atom 10656O LYS B176-83.990-35.370-34.9721.0049.88O

Atom 10658N GLU B177-84.473-36.729-33.2541.0049.46N

Atom 10659 CA GLU B177-83.769-35.959-32.2211.0048.92C

Atom 10661 CB GLU B177-84.628-35.813-30.9461.0049.03C

Atom 10664 CG GLU B177-84.196-36.691-29.7321.0049.60C

Atom 10667 CD GLU B177-85.278-36.871-28.6621.0050.10C

Atom 10668 OE1 GLU B177-84.998-37.576-27.6701.0049.78O

Atom 10669 OE2 GLU B177-86.401-36.336-28.8081.0050.78O

Atom 10670C GLU B177-82.469-36.703-31.9241.0048.19C

Atom 10671O GLU B177-81.421-36.085-31.7211.0048.68O

Atom 10673N LEU B178-82.557-38.037-31.9001.0046.98N

Atom 10674 CA LEU B178-81.398-38.924-31.8171.0045.91C

Atoms 10676 CB LEU B178-81.838-40.387-31.9451.0045.70C

Atom 10679 CG LEU B178-81.111-41.408-31.0741.0045.24C

Atom 10681 CD1 LEU B178-81.498-41.225-29.6091.0044.88C

Atom 10685 CD2 LEU B178-81.413-42.826-31.5391.0044.19C

Atoms 10689C LEU B178-80.423-38.571-32.9341.0045.27C

Atom 10690O LEU B178-79.211-38.624-32.7591.0044.99O

Atom 10692N ALA B179-80.970-38.203-34.0881.0044.75N

Atom 10693 CA ALA B179-80.174-37.661-35.1811.0044.24C

Atom 10695 CB ALA B179-81.088-37.069-36.2311.0044.30C

Atom 10699C ALA B179-79.192-36.602-34.6831.0043.65C

Atom 10700O ALA B179-78.028-36.604-35.0611.0043.56O

Atom 10702N GLU B180-79.675-35.707-33.8271.0043.01N

Atom 10703 CA GLU B180-78.863-34.610-33.3111.0042.49C

Atom 10705 CB GLU B180-79.749-33.477-32.7891.0042.85C

Atom 10708 CG GLU B180-80.574-32.800-33.8811.0044.23C

Atom 10711 CD GLU B180-80.991-31.382-33.5191.0045.80C

Atom 10712 OE1 GLU B180-80.098-30.580-33.1561.0046.69O

Atom 10713 OE2 GLU B180-82.203-31.065-33.6101.0046.71O

Atom 10714C GLU B180-77.944-35.075-32.2101.0041.39C

Atom 10715O GLU B180-76.843-34.562-32.0711.0041.27O

Atom 10717N GLN B181-78.404-36.035-31.4191.0040.20N

Atom 10718 CA GLN B181-77.570-36.632-30.3941.0039.45C

Atom 10720 CB GLN B181-78.280-37.809-29.7361.0039.88C

Atom 10723 CG GLN B181-78.005-37.959-28.2491.0041.64C

Atom 10726 CD GLN B181-78.873-37.036-27.4041.0044.00C

Atom 10727 OE1 GLN B181-80.109-36.992-27.5811.0045.65O

Atom 10728 NE2 GLN B181-78.235-36.291-26.4741.0043.41N

Atom 10731C GLN B181-76.270-37.120-31.0031.0038.28C

Atom 10732O GLN B181-75.203-36.767-30.5231.0038.27O

Atoms 10734N VAL B182-76.358-37.911-32.0721.0037.05N

Atom 10735 CA VAL B182-75.160-38.515-32.6751.0036.20C

Atom 10737 CB VAL B182-75.486-39.661-33.6811.0036.11C

Atom 10739 CG1 VAL B182-76.493-40.641-33.0801.0036.13C

Atom 10743 CG2 VAL B182-75.977-39.106-35.0041.0036.06C

Atom 10747C VAL B182-74.238-37.495-33.3641.0035.44C

Atom 10748O VAL B182-73.012-37.682-33.3751.0035.19O

Atom 10750N SER B183-74.811-36.432-33.9361.0034.41N

Atom 10751 CA SER B183-73.998-35.416-34.6301.0033.74C

Atom 10753 CB SER B183-74.858-34.438-35.4221.0033.58C

Atom 10756 OG SER B183-76.003-35.085-35.9251.0034.52O

Atom 10758C SER B183-73.184-34.644-33.6251.0032.88C

Atom 10759O SER B183-72.055-34.251-33.9061.0033.25O

Atom 10761N HIS B184-73.788-34.427-32.4611.0031.83N

Atom 10762 CA HIS B184-73.150-33.787-31.3261.0030.98C

Atom 10764 CB HIS B184-74.188-33.627-30.2121.0031.14C

Atom 10767 CG HIS B184-73.710-32.849-29.0301.0031.91C

Atom 10768 ND1 HIS B184-73.326-31.527-29.1141.0033.18N

Atom 10770 CE1 HIS B184-72.960-31.107-27.9141.0033.10C

Atom 10772 NE2 HIS B184-73.106-32.102-27.0561.0031.85N

Atom 10774 CD2 HIS B184-73.583-33.200-27.7271.0031.86C

Atom 10776C HIS B184-71.968-34.632-30.8651.0030.13C

Atom 10777O HIS B184-70.863-34.122-30.7091.0029.95O

Atom 10779N ALA B185-72.194-35.931-30.6831.0029.27N

Atom 10780 CA ALA B185-71.123-36.856-30.2811.0028.64C

Atom 10782 CB ALA B185-71.689-38.233-29.9861.0028.44C

Atom 10786C ALA B185-70.017-36.965-31.3301.0028.08C

Atom 10787O ALA B185-68.839-37.043-30.9921.0028.26O

Atom 10789N LEU B186-70.394-36.984-32.6021.0027.40N

Atom 10790 CA LEU B186-69.412-37.101-33.6741.0026.84C

Atom 10792 CB LEU B186-70.088-37.481-35.0001.0026.75C

Atom 10795 CG LEU B186-70.085-38.983-35.3201.0026.70C

Atom 10797 CD1 LEU B186-70.214-39.868-34.0751.0027.07C

Atoms 10801 CD2 LEU B186-71.179-39.306-36.3031.0026.29C

Atoms 10805C LEU B186-68.594-35.822-33.8151.0026.45C

Atom 10806O LEU B186-67.449-35.875-34.2371.0026.48O

Atom 10808N GLU B187-69.186-34.685-33.4541.0025.93N

Atom 10809 CA GLU B187-68.479-33.406-33.4031.0025.57C

Atom 10811 CB GLU B187-69.447-32.310-32.9621.0025.61C

Atom 10814 CG GLU B187-69.035-30.899-33.3251.0026.29C

Atom 10817 CD GLU B187-69.930-29.857-32.6711.0027.10C

Atom 10818 OE1 GLU B187-70.312-30.057-31.4871.0026.51O

Atom 10819 OE2 GLU B187-70.251-28.846-33.3441.0027.54O

Atom 10820C GLU B187-67.307-33.490-32.4181.0025.13C

Atom 10821O GLU B187-66.155-33.165-32.7491.0024.85O

Atoms 10823N LEU B188-67.625-33.938-31.2041.0024.58N

Atom 10824 CA LEU B188-66.644-34.137-30.1481.0024.06C

Atom 10826 CB LEU B188-66.343-32.817-29.4511.0024.12C

Atom 10829 CG LEU B188-65.042-32.714-28.6701.0023.61C

Atoms 10831 CD1 LEU B188-63.895-32.872-29.6291.0023.12C

Atom 10835 CD2 LEU B188-64.976-31.368-27.9641.0023.18C

Atoms 10839C LEU B188-67.248-35.087-29.1401.0023.70C

Atom 10840O LEU B188-68.392-34.901-28.7431.0023.68O

Atom 10842N PRO B189-66.493-36.106-28.7131.0023.34N

Atom 10843 CA PRO B189-67.031-36.983-27.6921.0023.08C

Atom 10845 CB PRO B189-66.018-38.115-27.6381.0022.96C

Atom 10848 CG PRO B189-64.743-37.452-27.9401.0023.22C

Atom 10851 CD PRO B189-65.059-36.350-28.9291.0023.54C

Atom 10854C PRO B189-67.053-36.229-26.3871.0022.86C

Atom 10855O PRO B189-66.284-35.285-26.2151.0023.03O

Atom 10856N LEU B190-67.912-36.628-25.4651.0022.56N

Atoms 10857 CA LEU B190-68.152-35.773-24.3231.0022.41C

Atom 10859 CB LEU B190-69.567-35.970-23.7661.0023.04C

Atom 10862 CG LEU B190-69.853-37.136-22.8481.0023.41C

Atom 10864 CD1 LEU B190-69.303-36.733-21.4811.0025.02C

Atom 10868 CD2 LEU B190-71.342-37.411-22.8201.0021.69C

Atoms 10872C LEU B190-67.065-35.899-23.2661.0021.56C

Atom 10873O LEU B190-66.860-34.976-22.4771.0021.67O

Atom 10875N HIS B191-66.320-36.998-23.2831.0020.39N

Atom 10876 CA HIS B191-65.089-37.037-22.4901.0019.40C

Atom 10878 CB HIS B191-64.399-38.393-22.5971.0019.19C

Atom 10881 CG HIS B191-63.222-38.530-21.6891.0019.32C

Atom 10882 ND1 HIS B191-63.347-38.562-20.3171.0020.95N

Atoms 10884 CE1 HIS B191-62.145-38.659-19.7711.0021.15C

Atom 10886 NE2 HIS B191-61.245-38.689-20.7411.0019.36N

Atom 10888 CD2 HIS B191-61.893-38.604-21.9481.0019.49C

Atom 10890C HIS B191-64.094-35.913-22.8411.0018.62C

Atom 10891O HIS B191-63.150-35.677-22.0851.0018.59O

Atom 10893N ARG B192-64.307-35.216-23.9571.0017.72N

Atom 10894 CA ARG B192-63.394-34.150-24.3941.0017.57C

Atom 10896 CB ARG B192-62.838-34.504-25.7731.0017.81C

Atom 10899 CG ARG B192-61.971-35.736-25.7811.0018.59C

Atom 10902 CD ARG B192-61.484-36.067-27.1811.0020.10C

Atom 10905 NE ARG B192-60.462-37.116-27.1651.0021.62N

Atom 10907 CZ ARG B192-59.919-37.648-28.2541.0022.77C

Atom 10908 NH1 ARG B192-60.304-37.248-29.4541.0024.20N

Atom 10911 NH2 ARG B192-58.987-38.581-28.1491.0023.37N

Atom 10914C ARG B192-63.983-32.726-24.4401.0017.01C

Atom 10915O ARG B192-63.242-31.739-24.5261.0015.78O

Atom 10917N ARG B193-65.309-32.634-24.3921.0017.01N

Atom 10918 CA ARG B193-66.015-31.350-24.4531.0016.99C

Atom 10920 CB ARG B193-67.476-31.582-24.8921.0017.29C

Atom 10923 CG ARG B193-68.192-30.318-25.3771.0018.42C

Atom 10926 CD ARG B193-69.664-30.559-25.6461.0019.63C

Atom 10929 NE ARG B193-69.912-31.592-26.6481.0021.16N

Atom 10931 CZ ARG B193-69.868-31.398-27.9711.0023.56C

Atom 10932 NH1 ARG B193-69.575-30.210-28.4961.0023.37N

Atom 10935 NH2 ARG B193-70.112-32.413-28.7891.0025.37N

Atom 10938C ARG B193-65.974-30.658-23.0871.0016.46C

Atom 10939O ARG B193-66.040-31.323-22.0341.0016.47O

Atom 10941N THR B194-65.864-29.335-23.0781.0015.84N

Atom 10942 CA THR B194-65.886-28.629-21.7991.0015.67C

Atom 10944 CB THR B194-65.354-27.199-21.8841.0015.48C

Atom 10946 OG1 THR B194-66.077-26.478-22.8821.0015.55O

Atom 10948 CG2 THR B194-63.877-27.189-22.2111.0014.65C

Atom 10952C THR B194-67.310-28.613-21.2701.0015.79C

Atom 10953O THR B194-68.264-28.652-22.0301.0015.73O

Atoms 10955N GLN B195-67.444-28.557-19.9571.0016.20N

Atom 10956 CA GLN B195-68.737-28.711-19.3281.0016.84C

Atoms 10958 CB GLN B195-68.601-28.781-17.8161.0017.07C

Atom 10961 CG GLN B195-69.921-28.440-17.1531.0018.86C

Atom 10964 CD GLN B195-69.999-28.875-15.7461.0020.95C

Atom 10965 OE1 GLN B195-69.099-29.511-15.2451.0024.63O

Atom 10966 NE2 GLN B195-71.071-28.529-15.0821.0022.36N

Atom 10969C GLN B195-69.757-27.623-19.6691.0016.93C

Atom 10970O GLN B195-70.858-27.931-20.1361.0016.98O

Atom 10972N ARG B196-69.430-26.366-19.3861.0016.92N

Atom 10973 CA ARG B196-70.358-25.301-19.6851.0017.06C

Atom 10975 CB ARG B196-69.719-23.932-19.4591.0017.00C

Atom 10978 CG ARG B196-70.095-23.289-18.1201.0017.09C

Atom 10981 CD ARG B196-70.283-24.320-16.9951.0017.56C

Atom 10984 NE ARG B196-71.452-24.043-16.1461.0017.64N

Atom 10986 CZ ARG B196-72.289-24.965-15.6641.0017.93C

Atom 10987 NH1 ARG B196-72.136-26.244-15.9661.0017.72N

Atom 10990 NH2 ARG B196-73.305-24.611-14.8781.0018.27N

Atom 10993C ARG B196-70.881-25.481-21.0981.0017.42C

Atom 10994O ARG B196-72.079-25.519-21.3171.0017.66O

Atoms 10996N LEU B197-69.984-25.676-22.0441.0018.04N

Atom 10997 CA LEU B197-70.379-25.925-23.4251.0018.51C

Atom 10999 CB LEU B197-69.133-26.085-24.2891.0018.52C

Atom 11002 CG LEU B197-68.998-25.185-25.5081.0018.06C

Atom 11004 CD1 LEU B197-68.209-23.932-25.2051.0015.52C

Atom 11008 CD2 LEU B197-68.293-26.002-26.5741.0020.21C

Atom 11012C LEU B197-71.290-27.163-23.5801.0019.14C

Atom 11013O LEU B197-72.226-27.150-24.3721.0019.52O

Atom 11015N GLU B198-71.030-28.235-22.8421.0019.72N

Atom 11016 CA GLU B198-71.918-29.396-22.9091.0020.43C

Atom 11018 CB GLU B198-71.272-30.631-22.2701.0020.65C

Atom 11021 CG GLU B198-72.176-31.880-22.1721.0022.51C

Atom 11024 CD GLU B198-72.635-32.460-23.5221.0025.57C

Atom 11025 OE1 GLU B198-72.315-31.896-24.5811.0028.90O

Atom 11026 OE2 GLU B198-73.326-33.506-23.5401.0028.09O

Atom 11027C GLU B198-73.271-29.101-22.2591.0020.72C

Atom 11028O GLU B198-74.281-29.693-22.6441.0020.82O

11030N ALA B199-73.282-28.199-21.2701.0020.86N atoms

Atom 11031 CA ALA B199-74.508-27.814-20.5651.0020.66C

Atom 11033 CB ALA B199-74.176-27.013-19.3261.0020.36C

Atom 11037C ALA B199-75.472-27.033-21.4611.0020.84C

Atom 11038O ALA B199-76.644-27.404-21.5901.0020.84O

Atom 11040N VAL B200-75.002-25.961-22.0921.0021.12N

Atom 11041 CA VAL B200-75.903-25.177-22.9421.0021.60C

Atom 11043 CB VAL B200-75.215-24.042-23.7011.0021.30C

Atom 11045 CG1 VAL B200-74.660-23.055-22.7381.0021.26C

Atom 11049 CG2 VAL B200-74.135-24.575-24.6261.0021.28C

Atom 11053C VAL B200-76.603-26.077-23.9441.0022.32C

Atom 11054O VAL B200-77.791-25.908-24.2181.0022.32O

Atom 11056N TRP B201-75.872-27.047-24.4721.0023.16N

Atom 11057 CA TRP B201-76.441-27.946-25.4541.0024.02C

Atom 11059 CB TRP B201-75.348-28.718-26.1951.0024.36C

Atom 11062 CG TRP B201-75.898-29.510-27.3311.0024.84C

Atom 11063 CD1 TRP B201-76.060-29.092-28.6131.0025.41C

Atom 11065 NE1 TRP B201-76.599-30.094-29.3741.0025.61N

Atom 11067 CE2 TRP B201-76.807-31.184-28.5791.0025.34C

Atom 11068 CD2 TRP B201-76.374-30.847-27.2791.0025.56C

Atom 11069 CE3 TRP B201-76.466-31.800-26.2641.0027.13C

Atom 11071 CZ3 TRP B201-76.989-33.046-26.5741.0028.66C

Atom 11073 CH2 TRP B201-77.419-33.347-27.8851.0028.01C

Atom 11075 CZ2 TRP B201-77.332-32.425-28.8941.0026.09C

Atom 11077C TRP B201-77.411-28.938-24.8331.0024.22C

Atom 11078O TRP B201-78.473-29.172-25.3831.0024.83O

Atom 11080N SER B202-77.034-29.541-23.7151.0024.39N

Atom 11081 CA SER B202-77.818-30.626-23.1441.0024.50C

Atom 11083 CB SER B202-76.968-31.455-22.1841.0024.42C

Atom 11086 OG SER B202-75.848-32.021-22.8481.0023.80O

Atom 11088C SER B202-79.067-30.099-22.4411.0024.98C

Atom 11089O SER B202-80.057-30.816-22.3241.0024.73O

Atom 11091N ILE B203-79.032-28.849-21.9821.0025.60N

Atom 11092 CA ILE B203-80.219-28.255-21.3721.0025.98C

Atom 11094 CB ILE B203-79.908-26.967-20.5911.0025.85C

Atom 11096 CG1 ILE B203-79.086-27.326-19.3481.0025.76C

Atom 11099 CD1 ILE B203-78.779-26.159-18.4311.0026.28C

Atom 11103 CG2 ILE B203-81.212-26.253-20.2061.0024.51C

Atom 11107C ILE B203-81.280-28.016-22.4431.0026.67C

Atom 11108O ILE B203-82.428-28.398-22.2601.0026.96O

Atom 11110N GLU B204-80.879-27.412-23.5631.0027.30N

Atom 11111 CA GLU B204-81.758-27.205-24.7201.0027.49C

Atom 11113 CB GLU B204-81.036-26.384-25.8041.0027.67C

Atom 11116 CG GLU B204-81.849-26.077-27.0731.0028.50C

Atom 11119 CD GLU B204-82.987-25.072-26.8551.0029.81C

Atom 11120 OE1 GLU B204-83.158-24.600-25.7111.0031.40O

Atom 11121 OE2 GLU B204-83.710-24.750-27.8321.0029.57O

Atom 11122C GLU B204-82.201-28.542-25.2871.0027.52C

Atom 11123O GLU B204-83.321-28.667-25.7381.0027.67O

Atom 11125N ALA B205-81.326-29.539-25.2661.0027.74N

Atom 11126 CA ALA B205-81.684-30.872-25.7281.0028.09C

Atom 11128 CB ALA B205-80.472-31.789-25.7261.0027.75C

Atom 11132C ALA B205-82.771-31.448-24.8391.0028.81C

Atom 11133O ALA B205-83.811-31.877-25.3251.0028.90O

Atom 11135N TYR B206-82.517-31.433-23.5311.0029.72N

Atom 11136 CA TYR B206-83.408-32.020-22.5271.0030.30C

Atom 11138 CB TYR B206-82.760-31.915-21.1491.0030.24C

Atom 11141 CG TYR B206-83.276-32.889-20.1271.0029.79C

Atom 11142 CD1 TYR B206-83.055-34.245-20.2861.0030.71C

Atom 11144 CE1 TYR B206-83.498-35.161-19.3601.0030.78C

Atom 11146 CZ TYR B206-84.159-34.731-18.2381.0030.03C

Atom 11147 OH TYR B206-84.582-35.684-17.3431.0030.51O

Atom 11149 CE2 TYR B206-84.394-33.379-18.0421.0029.42C

Atom 11151 CD2 TYR B206-83.945-32.463-18.9891.0029.05C

Atom 11153C TYR B206-84.744-31.308-22.4671.0031.19C

Atom 11154O TYR B206-85.790-31.930-22.3111.0031.44O

Atom 11156N ARG B207-84.683-29.988-22.5581.0032.21N

Atom 11157 CA ARG B207-85.853-29.128-22.5211.0033.04C

Atom 11159 CB ARG B207-85.394-27.700-22.8431.0032.86C

Atom 11162 CG ARG B207-86.441-26.637-22.8461.0032.82C

Atom 11165 CD ARG B207-85.905-25.360-23.4621.0032.76C

Atom 11168 NE ARG B207-85.148-24.561-22.5041.0032.80N

Atom 11170 CZ ARG B207-85.676-23.709-21.6281.0033.40C

Atom 11171 NH1 ARG B207-86.989-23.526-21.5551.0034.29N

Atom 11174 NH2 ARG B207-84.884-23.030-20.8081.0033.89N

Atom 11177C ARG B207-86.971-29.606-23.4781.0034.14C

Atom 11178O ARG B207-88.144-29.521-23.1281.0034.34O

Atom 11180N LYS B208-86.607-30.137-24.6521.0035.32N

Atom 11181 CA LYS B208-87.581-30.535-25.6881.0036.16C

Atom 11183 CB LYS B208-86.960-30.468-27.0901.0036.01C

Atom 11186 CG LYS B208-86.126-29.234-27.3681.0035.85C

Atom 11189 CD LYS B208-85.934-29.023-28.8611.0035.98C

Atom 11192 CE LYS B208-84.774-28.086-29.1861.0035.63C

Atom 11195 NZ LYS B208-83.566-28.843-29.5961.0035.17N

Atom 11199C LYS B208-88.166-31.937-25.4901.0037.25C

Atom 11200O LYS B208-89.212-32.250-26.0541.0037.50O

Atom 11202N LYS B209-87.484-32.788-24.7301.0038.58N

Atom 11203 CA LYS B209-88.026-34.106-24.3831.0039.89C

Atom 11205 CB LYS B209-87.013-34.923-23.5781.0040.23C

Atom 11208 CG LYS B209-85.914-35.604-24.3731.0041.47C

Atom 11211 CD LYS B209-84.858-36.178-23.4171.0043.71C

Atom 11214 CE LYS B209-84.448-37.612-23.7641.0045.15C

Atom 11217 NZ LYS B209-85.390-38.621-23.1631.0045.73N

Atom 11221C LYS B209-89.288-33.950-23.5301.0040.51C

Atom 11222O LYS B209-89.230-33.367-22.4411.0040.84O

Atoms 11224N GLU B210-90.418-34.477-24.0001.0040.92N

Atom 11225 CA GLU B210-91.652-34.386-23.2231.0041.27C

Atoms 11227 CB GLU B210-92.855-34.935-23.9981.0041.77C

Atom 11230 CG GLU B210-92.822-36.446-24.2651.0043.47C

Atom 11233 CD GLU B210-94.049-36.922-25.0321.0045.23C

Atom 11234 OE1 GLU B210-95.188-36.590-24.6121.0045.02O

Atom 11235 OE2 GLU B210-93.863-37.629-26.0531.0046.74O

Atoms 11236C GLU B210-91.494-35.121-21.8951.0040.71C

Atom 11237O GLU B210-91.996-34.667-20.8641.0040.99O

Atom 11239N ASP B211-90.773-36.240-21.9241.0039.76N

Atom 11240 CA ASP B211-90.533-37.050-20.7211.0038.96C

Atom 11242 CB ASP B211-90.151-38.476-21.1231.0039.10C

Atom 11245 CG ASP B211-89.101-38.499-22.2121.0040.26C

Atom 11246 OD1 ASP B211-89.327-37.827-23.2541.0041.25O

Atom 11247 OD2 ASP B211-88.055-39.160-22.0201.0041.66O

Atom 11248C ASP B211-89.440-36.468-19.8261.0037.75C

Atom 11249O ASP B211-89.009-37.131-18.8921.0037.62O

Atom 11251N ALA B212-88.989-35.245-20.1151.0036.47N

Atom 11252 CA ALA B212-87.941-34.587-19.3351.0035.36C

Atom 11254 CB ALA B212-87.516-33.294-20.0111.0035.23C

Atom 11258C ALA B212-88.423-34.307-17.9201.0034.40C

Atom 11259O ALA B212-89.559-33.870-17.7281.0034.42O

Atom 11261N ASN B213-87.565-34.574-16.9371.0033.24N

Atom 11262 CA ASN B213-87.890-34.333-15.5331.0032.67C

Atom 11264 CB ASN B213-86.840-34.986-14.6231.0032.58C

Atom 11267 CG ASN B213-87.204-34.912-13.1521.0032.67C

Atom 11268 OD1 ASN B213-87.891-33.994-12.7221.0032.62O

Atom 11269 ND2 ASN B213-86.734-35.882-12.3711.0033.18N

Atoms 11272C ASN B213-87.990-32.825-15.2661.0032.19C

Atom 11273O ASN B213-87.010-32.092-15.3761.0032.38O

Atoms 11275N GLN B214-89.182-32.356-14.9231.0031.48N

Atom 11276 CA GLN B214-89.389-30.924-14.7561.0030.85C

Atom 11278 CB GLN B214-90.889-30.581-14.6931.0030.82C

Atom 11281 CG GLN B214-91.684-30.869-16.0021.0030.80C

Atom 11284 CD GLN B214-90.990-30.378-17.2911.0029.69C

Atom 11285 OE1 GLN B214-90.893-29.174-17.5431.0029.07O

Atom 11286 NE2 GLN B214-90.526-31.321-18.1131.0027.71N

Atom 11289C GLN B214-88.638-30.369-13.5431.0030.37C

Atom 11290O GLN B214-88.263-29.200-13.5331.0030.80O

Atom 11292N VAL B215-88.393-31.200-12.5321.0029.54N

Atom 11293 CA VAL B215-87.566-30.779-11.3951.0028.56C

Atom 11295 CB VAL B215-87.564-31.818-10.2601.0028.64C

Atom 11297 CG1 VAL B215-86.758-31.299-9.0751.0027.94C

Atom 11301 CG2 VAL B215-88.999-32.167-9.8561.0028.26C

Atom 11305C VAL B215-86.124-30.545-11.8451.0027.63C

Atom 11306O VAL B215-85.566-29.472-11.6151.0027.58O

Atom 11308N LEU B216-85.546-31.548-12.5041.0026.37N

Atoms 11309 CA LEU B216-84.143-31.509-12.9301.0025.47C

Atom 11311 CB LEU B216-83.714-32.866-13.4901.0025.46C

Atom 11314 CG LEU B216-82.274-32.995-13.9791.0024.97C

Atom 11316 CD1 LEU B216-81.289-32.640-12.8831.0024.62C

Atom 11320 CD2 LEU B216-82.042-34.407-14.4721.0024.55C

Atom 11324C LEU B216-83.861-30.447-13.9721.0024.68C

Atom 11325O LEU B216-82.819-29.820-13.9291.0024.91O

Atom 11327N LEU B217-84.776-30.269-14.9161.0023.79N

Atom 11328 CA LEU B217-84.625-29.260-15.9601.0023.13C

Atom 11330 CB LEU B217-85.765-29.384-16.9721.0023.36C

Atom 11333 CG LEU B217-85.808-28.374-18.1231.0023.18C

Atom 11335 CD1 LEU B217-84.462-28.268-18.7961.0022.69C

Atom 11339 CD2 LEU B217-86.861-28.786-19.1261.0023.38C

Atom 11343C LEU B217-84.631-27.853-15.3831.0022.51C

Atom 11344O LEU B217-83.903-26.973-15.8551.0022.08O

Atoms 11346N GLU B218-85.481-27.647-14.3751.0021.84N

Atom 11347 CA GLU B218-85.619-26.339-13.7251.0021.26C

Atom 11349 CB GLU B218-86.813-26.341-12.7681.0021.27C

Atom 11352 CG GLU B218-87.206-24.956-12.2461.0021.35C

Atom 11355 CD GLU B218-88.501-24.964-11.4411.0020.89C

Atom 11356 OE1 GLU B218-89.097-26.052-11.2631.0020.47O

Atom 11357 OE2 GLU B218-88.915-23.874-10.9861.0020.15O

Atom 11358C GLU B218-84.348-26.001-12.9691.0020.58C

Atom 11359O GLU B218-83.877-24.865-12.9821.0020.31O

Atoms 11361N LEU B219-83.802-27.015-12.3121.0019.87N

Atom 11362 CA LEU B219-82.559-26.885-11.5921.0019.12C

Atom 11364 CB LEU B219-82.310-28.132-10.7461.0018.58C

Atom 11367 CG LEU B219-81.159-28.054-9.7621.0017.07C

Atom 11369 CD1 LEU B219-81.321-26.847-8.8721.0016.10C

Atom 11373 CD2 LEU B219-81.107-29.311-8.9541.0015.22C

Atoms 11377C LEU B219-81.443-26.675-12.5991.0019.16C

Atom 11378O LEU B219-80.684-25.721-12.4781.0019.42O

Atom 11380N ALA B220-81.368-27.546-13.6061.0019.04N

Atom 11381 CA ALA B220-80.356-27.431-14.6691.0019.04C

Atom 11383 CB ALA B220-80.648-28.398-15.8171.0018.64C

Atom 11387C ALA B220-80.257-26.004-15.1961.0019.06C

Atom 11388O ALA B220-79.159-25.472-15.3211.0019.08O

Atom 11390N ILE B221-81.410-25.393-15.4751.0019.19N

Atom 11391 CA ILE B221-81.473-24.016-15.9631.0019.22C

Atom 11393 CB ILE B221-82.898-23.638-16.4231.0019.03C

Atom 11395 CG1 ILE B221-83.229-24.323-17.7551.0018.52C

Atom 11398 CD1 ILE B221-84.687-24.645-17.9281.0017.52C

Atom 11402 CG2 ILE B221-83.024-22.121-16.5641.0018.03C

Atom 11406C ILE B221-81.030-23.013-14.9061.0019.62C

Atom 11407O ILE B221-80.137-22.190-15.1361.0019.53O

Atom 11409N LEU B222-81.666-23.096-13.7451.0020.27N

Atom 11410 CA LEU B222-81.412-22.161-12.6541.0020.63C

Atom 11412 CB LEU B222-82.203-22.561-11.4121.0020.50C

Atom 11415 CG LEU B222-82.195-21.523-10.2961.0020.76C

Atom 11417 CD1 LEU B222-83.439-21.675-9.4311.0021.02C

Atoms 11421 CD2 LEU B222-80.924-21.625-9.4531.0020.21C

Atoms 11425C LEU B222-79.925-22.089-12.3411.0020.98C

Atom 11426O LEU B222-79.337-21.011-12.3811.0021.40O

Atom 11428N ASP B223-79.319-23.240-12.0641.0021.24N

Atom 11429 CA ASP B223-77.907-23.298-11.7091.0021.48C

Atom 11431 CB ASP B223-77.509-24.724-11.3141.0021.66C

Atom 11434 CG ASP B223-76.168-24.792-10.5891.0022.70C

Atom 11435 OD1 ASP B223-75.095-24.775-11.2441.0024.25O

Atom 11436 OD2 ASP B223-76.190-24.893-9.3491.0024.85O

Atom 11437C ASP B223-77.017-22.768-12.8351.0021.64C

Atom 11438O ASP B223-76.035-22.104-12.5481.0021.66O

Atom 11440N TYR B224-77.361-23.023-14.1001.0022.07N

Atom 11441 CA TYR B224-76.517-22.561-15.2181.0022.47C

Atom 11443 CB TYR B224-76.980-23.111-16.5891.0022.35C

Atom 11446 CG TYR B224-76.032-22.733-17.7241.0022.25C

Atom 11447 CD1 TYR B224-75.002-23.576-18.1161.0021.46C

Atom 11449 CE1 TYR B224-74.126-23.216-19.1351.0021.43C

Atom 11451 CZ TYR B224-74.260-21.991-19.7611.0021.62C

Atom 11452 OH TYR B224-73.387-21.618-20.7601.0020.46O

Atom 11454 CE2 TYR B224-75.270-21.132-19.3871.0022.04C

Atom 11456 CD2 TYR B224-76.144-21.500-18.3731.0022.73C

Atom 11458C TYR B224-76.414-21.023-15.2621.0023.06C

Atom 11459O TYR B224-75.323-20.467-15.5071.0022.89O

Atom 11461N ASN B225-77.543-20.350-15.0271.0023.66N

Atom 11462 CA ASN B225-77.593-18.884-15.0721.0024.16C

Atom 11464 CB ASN B225-79.040-18.367-15.1071.0024.12C

Atom 11467 CG ASN B225-79.778-18.761-16.3651.0023.89C

Atom 11468 OD1 ASN B225-79.182-18.877-17.4371.0024.33O

Atom 11469 ND2 ASN B225-81.088-18.965-16.2441.0022.05N

Atoms 11472C ASN B225-76.880-18.265-13.8811.0024.73C

Atom 11473O ASN B225-76.195-17.247-14.0271.0025.09O

Atom 11475N MET B226-77.067-18.864-12.7031.0025.15N

Atom 11476 CA MET B226-76.423-18.390-11.4791.0025.53C

Atom 11478 CB MET B226-76.806-19.278-10.2821.0026.11C

Atom 11481 CG MET B226-75.905-19.169-9.0231.0027.59C

Atom 11484 SD MET B226-75.676-20.788-8.2141.0030.67S

Atom 11485 CE MET B226-77.308-21.005-7.4761.0029.78C

Atom 11489C MET B226-74.920-18.380-11.6921.0025.16C

Atom 11490O MET B226-74.258-17.387-11.3911.0025.10O

Atoms 11492N ILE B227-74.388-19.473-12.2391.0024.88N

Atom 11493 CA ILE B227-72.944-19.564-12.5011.0024.70C

Atom 11495 CB ILE B227-72.476-20.994-12.8821.0024.45C

Atom 11497 CG1 ILE B227-72.656-21.947-11.6951.0023.80C

Atom 11500 CD1 ILE B227-72.094-23.332-11.8851.0021.97C

Atom 11504 CG2 ILE B227-71.030-20.969-13.2661.0024.90C

Atom 11508C ILE B227-72.529-18.550-13.5661.0024.45C

Atom 11509O ILE B227-71.578-17.810-13.3731.0024.42O

Atom 11511N GLN B228-73.264-18.484-14.6681.0024.31N

Atom 11512 CA GLN B228-73.038-17.414-15.6391.0024.19C

Atoms 11514 CB GLN B228-74.143-17.363-16.6881.0024.02C

Atom 11517 CG GLN B228-73.788-16.488-17.8641.0023.42C

Atom 11520 CD GLN B228-74.807-16.567-18.9831.0023.70C

Atom 11521 OE1 GLN B228-75.790-15.813-19.0151.0024.07O

Atom 11522 NE2 GLN B228-74.564-17.465-19.9271.0023.49N

Atoms 11525C GLN B228-72.913-16.037-14.9871.0024.37C

Atom 11526O GLN B228-72.145-15.210-15.4701.0024.45O

Atom 11528N SER B229-73.653-15.776-13.9091.0024.45N

Atom 11529 CA SER B229-73.578-14.459-13.2641.0024.76C

Atom 11531 CB SER B229-74.815-14.163-12.3971.0024.84C

Atom 11534 OG SER B229-74.711-14.718-11.0961.0025.81O

Atom 11536C SER B229-72.270-14.279-12.4691.0024.64C

Atom 11537O SER B229-71.726-13.172-12.4081.0024.95O

Atom 11539N VAL B230-71.751-15.350-11.8781.0024.20N

Atom 11540 CA VAL B230-70.415-15.277-11.2991.0023.99C

Atom 11542 CB VAL B230-70.006-16.581-10.5741.0023.92C

Atom 11544 CG1 VAL B230-68.546-16.510-10.1051.0023.71C

Atom 11548 CG2 VAL B230-70.923-16.853-9.4091.0023.52C

Atom 11552C VAL B230-69.386-14.966-12.4001.0024.12C

Atom 11553O VAL B230-68.397-14.291-12.1361.0024.01O

Atom 11555N TYR B231-69.612-15.461-13.6211.0024.30N

Atom 11556 CA TYR B231-68.672-15.235-14.7281.0024.53C

Atom 11558 CB TYR B231-68.997-16.104-15.9461.0024.08C

Atom 11561 CG TYR B231-68.892-17.605-15.7541.0023.29C

Atom 11562 CD1 TYR B231-68.173-18.168-14.7061.0023.08C

Atom 11564 CE1 TYR B231-68.073-19.547-14.5651.0022.01C

Atom 11566 CZ TYR B231-68.685-20.369-15.4791.0021.16C

Atom 11567 OH TYR B231-68.607-21.746-15.3531.0020.18O

Atom 11569 CE2 TYR B231-69.387-19.825-16.5231.0021.64C

Atom 11571 CD2 TYR B231-69.476-18.464-16.6621.0022.15C

Atom 11573C TYR B231-68.658-13.772-15.1661.0025.37C

Atom 11574O TYR B231-67.602-13.221-15.5281.0025.25O

Atom 11576N GLN B232-69.832-13.148-15.1291.0026.11N

Atom 11577 CA GLN B232-69.978-11.797-15.6221.0026.68C

Atom 11579 CB GLN B232-71.430-11.541-15.9951.0026.45C

Atom 11582 CG GLN B232-71.883-12.385-17.1761.0025.67C

Atom 11585 CD GLN B232-73.388-12.394-17.3811.0024.91C

Atom 11586 OE1 GLN B232-74.140-11.761-16.6371.0024.81O

Atom 11587 NE2 GLN B232-73.834-13.113-18.4071.0023.39N

Atoms 11590C GLN B232-69.445-10.802-14.5931.0027.90C

Atom 11591O GLN B232-68.909-9.752-14.9581.0027.96O

Atom 11593N ARG B233-69.572-11.145-13.3121.0029.35N

Atom 11594 CA ARG B233-68.908-10.396-12.2411.0030.59C

Atom 11596 CB ARG B233-69.490-10.775-10.8671.0030.99C

Atom 11599 CG ARG B233-68.824-10.114-9.6611.0032.72C

Atom 11602 CD ARG B233-69.695-10.210-8.3911.0035.70C

Atom 11605 NE ARG B233-70.162-11.578-8.0861.0038.29N

Atom 11607 CZ ARG B233-71.403-12.053-8.2761.0039.65C

Atom 11608 NH1 ARG B233-72.367-11.287-8.7871.0040.23N

Atom 11611 NH2 ARG B233-71.687-13.320-7.9491.0039.61N

Atom 11614C ARG B233-67.390-10.632-12.3031.0031.10C

Atom 11615O ARG B233-66.615-9.693-12.1811.0031.19O

Atom 11617N ASP B234-66.954-11.868-12.5171.0031.91N

Atom 11618 CA ASP B234-65.530-12.102-12.7501.0032.63C

Atom 11620 CB ASP B234-65.220-13.566-13.0901.0032.53C

Atom 11623 CG ASP B234-65.336-14.493-11.8941.0032.90C

Atom 11624 OD1 ASP B234-65.477-14.028-10.7461.0033.06O

Atom 11625 OD2 ASP B234-65.293-15.713-12.1071.0034.22O

Atom 11626C ASP B234-65.058-11.206-13.8861.0033.10C

Atom 11627O ASP B234-64.097-10.458-13.7231.0033.55O

Atoms 11629N LEU B235-65.753-11.256-15.0171.0033.49N

Atoms 11630 CA LEU B235-65.311-10.550-16.2161.0034.06C

Atoms 11632 CB LEU B235-66.139-10.996-17.4221.0033.80C

Atom 11635 CG LEU B235-65.769-10.403-18.7751.0032.13C

Atom 11637 CD1 LEU B235-64.303-10.679-19.0501.0030.94C

Atom 11641 CD2 LEU B235-66.670-10.959-19.8701.0029.93C

Atoms 11645C LEU B235-65.345-9.023-16.1031.0035.40C

Atom 11646O LEU B235-64.500-8.352-16.6821.0035.61O

Atom 11648N ARG B236-66.327-8.473-15.3861.0036.92N

Atom 11649 CA ARG B236-66.380-7.019-15.1371.0038.06C

Atom 11651 CB ARG B236-67.650-6.607-14.3671.0038.43C

Atom 11654 CG ARG B236-68.882-6.321-15.2301.0039.58C

Atom 11657 CD ARG B236-69.958-5.520-14.4591.0040.93C

Atom 11660 NE ARG B236-70.383-6.149-13.1991.0041.74N

Atom 11662 CZ ARG B236-71.208-7.195-13.0951.0042.20C

Atom 11663 NH1 ARG B236-71.719-7.784-14.1751.0041.61N

Atom 11666 NH2 ARG B236-71.517-7.672-11.8921.0042.99N

Atom 11669C ARG B236-65.170-6.550-14.3431.0038.57C

Atom 11670O ARG B236-64.593-5.524-14.6651.0038.61O

Atom 11672N GLU B237-64.822-7.292-13.2911.0039.42N

Atom 11673 CA GLU B237-63.625-7.017-12.4801.0040.18C

Atom 11675 CB GLU B237-63.471-8.033-11.3171.0040.67C

Atom 11678 CG GLU B237-64.336-7.750-10.0571.0042.61C

Atom 11681 CD GLU B237-64.258-8.858-8.9611.0045.07C

Atom 11682 OE1 GLU B237-64.051-10.066-9.2821.0046.74O

Atom 11683 OE2 GLU B237-64.436-8.511-7.7641.0045.87O

Atoms 11684C GLU B237-62.352-7.024-13.3441.0039.93C

Atom 11685O GLU B237-61.593-6.050-13.3321.0039.96O

Atom 11687N THR B238-62.123-8.104-14.0951.0039.56N

Atom 11688 CA THR B238-60.900-8.200-14.8951.0039.42C

Atom 11690 CB THR B238-60.492-9.666-15.2681.0039.39C

Atom 11692 OG1 THR B238-61.222-10.123-16.4131.0039.37O

Atom 11694 CG2 THR B238-60.683-10.612-14.0951.0038.73C

Atom 11698C THR B238-60.961-7.326-16.1561.0039.48C

Atom 11699O THR B238-59.930-7.062-16.7611.0039.48O

Atom 11701N SER B239-62.149-6.871-16.5491.0039.62N

Atom 11702 CA SER B239-62.264-5.882-17.6311.0039.63C

Atom 11704 CB SER B239-63.689-5.810-18.1721.0039.56C

Atom 11707 OG SER B239-63.945-6.917-19.0101.0038.96O

Atom 11709C SER B239-61.796-4.496-17.1811.0039.99C

Atom 11710O SER B239-61.108-3.807-17.9331.0040.10O

Atom 11712N ARG B240-62.168-4.088-15.9651.0040.35N

Atom 11713 CA ARG B240-61.624-2.864-15.3631.0040.68C

Atom 11715 CB ARG B240-62.025-2.712-13.8811.0041.26C

Atom 11718 CG ARG B240-63.231-1.782-13.6211.0043.86C

Atom 11721 CD ARG B240-63.334-1.375-12.1301.0047.07C

Atom 11724 NE ARG B240-63.365-2.537-11.2221.0050.14N

Atom 11726 CZ ARG B240-64.462-3.077-10.6711.0052.32C

Atom 11727 NH1 ARG B240-64.342-4.141-9.8751.0053.16N

Atom 11730 NH2 ARG B240-65.677-2.577-10.8991.0053.18N

Atom 11733C ARG B240-60.113-2.914-15.4641.0039.91C

Atom 11734O ARG B240-59.490-2.000-15.9881.0039.86O

Atom 11736N TRP B241-59.541-4.002-14.9621.0039.14N

Atom 11737 CA TRP B241-58.105-4.217-15.0041.0038.37C

Atom 11739 CB TRP B241-57.773-5.635-14.5211.0038.17C

Atom 11742 CG TRP B241-56.373-6.005-14.7731.0036.58C

Atom 11743 CD1 TRP B241-55.290-5.668-14.0221.0036.32C

Atom 11745 NE1 TRP B241-54.152-6.176-14.5871.0035.63N

Atom 11747 CE2 TRP B241-54.494-6.846-15.7311.0034.31C

Atom 11748 CD2 TRP B241-55.883-6.757-15.8741.0033.99C

Atom 11749 CE3 TRP B241-56.484-7.357-16.9771.0033.28C

Atom 11751 CZ3 TRP B241-55.691-8.034-17.8831.0032.79C

Atom 11753 CH2 TRP B241-54.313-8.101-17.7201.0033.06C

Atom 11755 CZ2 TRP B241-53.697-7.515-16.6481.0034.16C

Atom 11757C TRP B241-57.561-3.999-16.4091.0038.25C

Atom 11758O TRP B241-56.607-3.252-16.6031.0038.13O

Atom 11760N TRP B242-58.186-4.644-17.3861.0038.21N

Atom 11761 CA TRP B242-57.695-4.628-18.7651.0038.27C

Atom 11763 CB TRP B242-58.479-5.640-19.6091.0038.31C

Atom 11766 CG TRP B242-57.948-5.872-20.9901.0038.61C

Atom 11767 CD1 TRP B242-58.642-5.754-22.1561.0039.11C

Atom 11769 NE1 TRP B242-57.828-6.046-23.2241.0039.31N

Atom 11771 CE2 TRP B242-56.582-6.363-22.7591.0038.95C

Atom 11772 CD2 TRP B242-56.617-6.263-21.3561.0038.66C

Atom 11773 CE3 TRP B242-55.454-6.528-20.6371.0038.98C

Atom 11775 CZ3 TRP B242-54.314-6.886-21.3261.0039.20C

Atom 11777 CH2 TRP B242-54.313-6.985-22.7161.0039.12C

Atom 11779 CZ2 TRP B242-55.434-6.724-23.4511.0039.22C

Atom 11781C TRP B242-57.739-3.241-19.4001.0038.27C

Atom 11782O TRP B242-56.814-2.873-20.1081.0037.81O

Atom 11784N ARG B243-58.809-2.489-19.1401.0038.79N

Atom 11785 CA ARG B243-58.936-1.097-19.6071.0039.37C

Atom 11787 CB ARG B243-60.351-, 552-19.3461.0039.66C

Atom 11790 CG ARG B243-61.324-., 792-20.5201.0041.96C

Atom 11793 CD ARG B243-62.687-1.338-20.0851.0044.82C

Atom 11796 NE ARG B243-63.461-, 380-19.2961.0047.15N

Atom 11798 CZ ARG B243-64.389-., 704-18.3861.0049.26C

Atom 11799 NH1 ARG B243-64.685-1.976-18.1091.0049.18N

Atom 11802 NH2 ARG B243-65.028.262-17.7291.0050.40N

Atom 11805C ARG B243-57.890-., 183-18.9801.0039.28C

Atom 11806O ARG B243-57.246.577-19.6811.0039.40O

Atom 11808N ARG B244-57.724-., 282-17.6651.0039.52N

Atom 11809 CA ARG B244-56.734.489-16.8881.0039.61C

Atom 11811 CB ARG B244-56.774.041-15.4091.0040.25C

Atom 11814 CG ARG B244-56.115.971-14.3831.0042.01C

Atom 11817 CD ARG B244-57.0292.154-14.0171.0044.39C

Atom 11820 NE ARG B244-56.3913.115-13.1031.0046.36N

Atom 11822 CZ ARG B244-55.4343.984-13.4411.0048.06C

Atom 11823 NH1 ARG B244-54.9514.043-14.6861.0048.90N

Atom 11826 NH2 ARG B244-54.9474.805-12.5191.0048.82N

Atom 11829C ARG B244-55.323.322-17.4371.0038.83C

Atom 11830O ARG B244-54.5941.300-17.5671.0038.39O

Atom 11832N VAL B245-54.953-., 922-17.7381.0038.52N

Atom 11833 CA VAL B245-53.694-1.241-18.4371.0038.43C

Atom 11835 CB VAL B245-53.491-2.760-18.6141.0038.31C

Atom 11837 CG1 VAL B245-53.247-3.426-17.2831.0037.77C

Atom 11841 CG2 VAL B245-52.344-3.036-19.5611.0037.66C

Atoms 11845C VAL B245-53.650-., 638-19.8321.0038.68C

Atom 11846O VAL B245-52.615-., 153-20.2471.0038.57O

Atom 11848N GLY B246-54.765-, 724-20.5591.0039.26N

Atom 11849 CA GLY B246-54.974-. 012-21.8341.0039.62C

Atoms 11852C GLY B246-53.962-., 262-22.9421.0040.08C

Atom 11853O GLY B246-53.617.650-23.7001.0039.89O

Atoms 11855N LEU B247-53.502-1.500-23.0621.0040.75N

Atoms 11856 CA LEU B247-52.347-1.778-23.9051.0041.34C

Atoms 11858 CB LEU B247-51.655-3.065-23.4591.0041.15C

Atom 11861 CG LEU B247-50.132-3.026-23.2981.0040.49C

Atom 11863 CD1 LEU B247-49.622-1.769-22.6051.0039.50C

Atom 11867 CD2 LEU B247-49.695-4.242-22.5261.0039.98C

Atoms 11871C LEU B247-52.744-1.836-25.3701.0042.50C

Atom 11872O LEU B247-52.005-1.358-26.2251.0042.33O

Atom 11874N ALA B248-53.925-2.390-25.6541.0044.14N

Atom 11875 CA ALA B248-54.439-2.494-27.0411.0045.16C

Atom 11877 CB ALA B248-55.705-3.347-27.0871.0045.15C

Atom 11881C ALA B248-54.692-1.140-27.7391.0045.98C

Atom 11882O ALA B248-54.604-1.053-28.9711.0046.37O

Atom 11884N THR B249-55.004-., 095-26.9751.0046.64N

Atom 11885 CA THR B249-55.1421.234-27.5701.0047.25C

Atom 11887 CB THR B249-55.9052.253-26.6551.0047.44C

Atom 11889 OG1 THR B249-55.0012.845-25.7061.0047.52O

Atom 11891 CG2 THR B249-57.1041.592-25.9281.0047.44C

Atom 11895C THR B249-53.7561.793-27.9311.0047.59C

Atom 11896O THR B249-53.5532.279-29.0491.0048.07O

Atom 11898N LYS B250-52.8081.710-26.9951.0047.67N

Atom 11899 CA LYS B250-51.4692.299-27.1851.0047.68C

Atom 11901 CB LYS B250-50.7932.553-25.8331.0047.68C

Atom 11904 CG LYS B250-51.4283.673-24.9991.0047.77C

Atom 11907 CD LYS B250-51.1425.086-25.5521.0047.59C

Atom 11910 CE LYS B250-49.6765.496-25.4411.0046.75C

Atom 11913 NZ LYS B250-49.4796.878-25.9481.0046.49N

Atom 11917C LYS B250-50.5411.465-28.0821.0047.72C

Atom 11918O LYS B250-49.5911.988-28.6631.0047.54O

Atom 11920N LEU B251-50.804.169-28.1841.0047.82N

Atom 11921 CA LEU B251-50.072-., 675-29.1181.0047.96C

Atoms 11923 CB LEU B251-49.584-1.970-28.4471.0048.04C

Atom 11926 CG LEU B251-48.109-2.064-28.0331.0047.39C

Atom 11928 CD1 LEU B251-47.659-. 881-27.1861.0046.47C

Atom 11932 CD2 LEU B251-47.894-3.376-27.3041.0046.78C

Atoms 11936C LEU B251-50.985-., 964-30.3061.0048.19C

Atom 11937O LEU B251-51.975-1.693-30.1941.0048.38O

Atom 11939N HIS B252-50.627-,. 396-31.4491.0048.42N

Atom 11940 CA HIS B252-51.521-., 329-32.6011.0048.62C

Atom 11942 CB HIS B252-51.110.850-33.4921.0048.99C

Atom 11945 CG HIS B252-51.0002.145-32.7421.0050.56C

Atom 11946 ND1 HIS B252-52.0952.935-32.4531.0052.11N

Atom 11948 CE1 HIS B252-51.7043.993-31.7661.0052.68C

Atom 11950 NE2 HIS B252-50.3973.912-31.5851.0052.86N

Atom 11952 CD2 HIS B252-49.9322.764-32.1811.0051.68C

Atom 11954C HIS B252-51.582-1.636-33.3831.0048.14C

Atom 11955O HIS B252-52.615-1.975-33.9351.0048.02O

Atom 11957N PHE B253-50.481-2.372-33.4051.0048.10N

Atom 11958 CA PHE B253-50.422-3.702-34.0441.0048.18C

Atom 11960 CB PHE B253-48.965-4.070-34.3751.0048.16C

Atom 11963 CG PHE B253-48.119-4.311-33.1631.0047.85C

Atom 11964 CD1 PHE B253-47.900-5.596-32.7021.0048.56C

Atom 11966 CE1 PHE B253-47.140-5.812-31.5761.0048.98C

Atom 11968 CZ PHE B253-46.602-4.729-30.8951.0048.50C

Atom 11970 CE2 PHE B253-46.817-3.454-31.3491.0047.40C

Atom 11972 CD2 PHE B253-47.569-3.249-32.4651.0047.22C

Atom 11974C PHE B253-51.038-4.819-33.1851.0048.30C

Atom 11975O PHE B253-51.344-5.903-33.6911.0047.63O

Atom 11977N ALA B254-51.204-4.541-31.8881.0048.86N

Atom 11978 CA ALA B254-51.653-5.531-30.9031.0049.13C

Atom 11980 CB ALA B254-51.290-5.071-29.4941.0049.02C

Atom 11984C ALA B254-53.153-5.806-30.9821.0049.46C

Atom 11985O ALA B254-53.967-4.870-31.0111.0049.50O

Atom 11987N ARG B255-53.501-7.097-31.0061.0049.75N

Atom 11988 CA ARG B255-54.896-7.549-30.9181.0049.89C

Atom 11990 CB ARG B255-55.028-9.051-31.2451.0049.94C

Atom 11993 CG ARG B255-54.839-9.439-32.7241.0049.93C

Atom 11996 CD ARG B255-54.709-10.967-32.9041.0049.79C

Atom 11999 NE ARG B255-53.527-11.505-32.2191.0050.11N

Atom 12001 CZ ARG B255-53.276-12.801-32.0101.0050.54C

Atom 12002 NH1 ARG B255-54.117-13.736-32.4391.0051.36N

Atom 12005 NH2 ARG B255-52.175-13.172-31.3601.0050.21N

Atom 12008C ARG B255-55.425-7.308-29.5111.0049.83C

Atom 12009O ARG B255-54.666-6.975-28.5991.0049.95O

Atom 12011N ASP B256-56.736-7.463-29.3501.0049.72N

Atom 12012 CA ASP B256-57.360-7.483-28.0341.0049.55C

Atom 12014 CB ASP B256-58.183-6.222-27.8121.0049.52C

Atom 12017 CG ASP B256-59.134-6.362-26.6541.0050.30C

Atom 12018 OD1 ASP B256-60.310-5.944-26.7801.0050.45O

Atom 12019 OD2 ASP B256-58.702-6.926-25.6221.0051.68O

Atom 12020C ASP B256-58.254-8.721-27.9311.0049.15C

Atom 12021O ASP B256-59.159-8.901-28.7371.0049.28O

Atom 12023N ARG B257-57.998-9.565-26.9371.0048.61N

Atom 12024 CA ARG B257-58.743-10.809-26.7651.0048.20C

Atom 12026 CB ARG B257-57.949-11.984-27.3731.0048.41C

Atom 12029 CG ARG B257-57.505-11.799-28.8211.0049.37C

Atom 12032 CD ARG B257-58.693-11.636-29.7841.0050.80C

Atom 12035 NE ARG B257-58.908-12.814-30.6271.0052.11N

Atom 12037 CZ ARG B257-58.678-12.876-31.9441.0052.99C

Atom 12038 NH1 ARG B257-58.214-11.820-32.6231.0052.37N

Atom 12041 NH2 ARG B257-58.918-14.016-32.5961.0052.97N

Atom 12044C ARG B257-59.032-11.089-25.2801.0047.32C

Atom 12045O ARG B257-58.579-12.101-24.7351.0047.46O

Atoms 12047N LEU B258-59.770-10.201-24.6161.0045.94N

Atom 12048 CA LEU B258-60.108-10.430-23.2051.0044.67C

Atom 12050 CB LEU B258-60.332-9.130-22.4381.0044.61C

Atom 12053 CG LEU B258-60.422-9.323-20.9201.0043.83C

Atoms 12055 CD1 LEU B258-59.045-9.552-20.3391.0043.48C

Atoms 12059 CD2 LEU B258-61.073-8.139-20.2621.0043.85C

Atoms 12063C LEU B258-61.347-11.286-23.0901.0043.49C

Atom 12064O LEU B258-61.375-12.220-22.2951.0043.84O

Atom 12066N ILE B259-62.364-10.968-23.8831.0041.92N

Atom 12067 CA ILE B259-63.617-11.711-23.8411.0040.80C

Atom 12069 CB ILE B259-64.718-11.132-24.7831.0041.05C

Atom 12071 CG1 ILE B259-64.852-9.598-24.6531.0041.61C

Atom 12074 CD1 ILE B259-65.200-8.874-25.9851.0042.16C

Atom 12078 CG2 ILE B259-66.065-11.816-24.4961.0040.46C

Atom 12082C ILE B259-63.319-13.151-24.2501.0039.50C

Atom 12083O ILE B259-63.782-14.082-23.5981.0039.30O

Atoms 12085N GLU B260-62.524-13.318-25.3161.0037.99N

Atom 12086 CA GLU B260-62.120-14.652-25.8121.0036.60C

Atom 12088 CB GLU B260-61.329-14.574-27.1421.0036.75C

Atom 12091 CG GLU B260-62.167-14.319-28.4251.0037.79C

Atom 12094 CD GLU B260-62.134-12.851-28.9051.0039.47C

Atoms 12095 OE1 GLU B260-62.207-11.923-28.0551.0039.97O

Atom 12096 OE2 GLU B260-62.033-12.628-30.1391.0040.31O

Atoms 12097C GLU B260-61.282-15.381-24.7701.0034.83C

Atom 12098O GLU B260-61.465-16.568-24.5441.0034.69O

Atom 12100N SER B261-60.365-14.669-24.1311.0032.89N

Atom 12101 CA SER B261-59.508-15.292-23.1391.0031.48C

Atom 12103 CB SER B261-58.341-14.376-22.7681.0031.55C

Atom 12106 OG SER B261-57.298-14.493-23.7281.0031.75O

Atom 12108C SER B261-60.294-15.716-21.9001.0030.04C

Atom 12109O SER B261-59.921-16.674-21.2081.0029.70O

Atom 12111N PHE B262-61.389-15.021-21.6181.0028.25N

Atom 12112 CA PHE B262-62.203-15.404-20.4801.0026.75C

Atom 12114 CB PHE B262-63.111-14.278-20.0091.0026.36C

Atom 12117 CG PHE B262-63.532-14.453-18.6031.0024.33C

Atom 12118 CD1 PHE B262-62.697-14.092-17.5841.0022.66C

Atom 12120 CE1 PHE B262-63.047-14.283-16.3011.0022.65C

Atom 12122 CZ PHE B262-64.245-14.873-16.0071.0023.93C

Atom 12124 CE2 PHE B262-65.076-15.267-17.0101.0024.08C

Atom 12126 CD2 PHE B262-64.711-15.067-18.3041.0023.96C

Atoms 12128C PHE B262-63.017-16.660-20.7511.0026.02C

Atom 12129O PHE B262-63.074-17.546-19.9091.0026.32O

Atom 12131N TYR B263-63.652-16.732-21.9151.0024.98N

Atom 12132 CA TYR B263-64.299-17.969-22.3961.0024.14C

Atom 12134 CB TYR B263-64.701-17.756-23.8531.0024.00C

Atom 12137 CG TYR B263-65.080-18.961-24.6671.0024.32C

Atom 12138 CD1 TYR B263-66.302-19.604-24.4891.0025.03C

Atom 12140 CE1 TYR B263-66.666-20.694-25.2851.0025.81C

Atom 12142 CZ TYR B263-65.798-21.132-26.2871.0027.06C

Atom 12143 OH TYR B263-66.106-22.191-27.1231.0027.14O

Atom 12145 CE2 TYR B263-64.590-20.489-26.4791.0026.80C

Atom 12147 CD2 TYR B263-64.250-19.404-25.6801.0025.65C

Atom 12149C TYR B263-63.351-19.162-22.2561.0023.35C

Atom 12150O TYR B263-63.712-20.219-21.7401.0022.80O

Atom 12152N TRP B264-62.119-18.955-22.7021.0022.64N

Atom 12153 CA TRP B264-61.047-19.918-22.5231.0021.95C

Atom 12155 CB TRP B264-59.737-19.334-23.0611.0021.84C

Atom 12158 CG TRP B264-58.603-20.278-22.9641.0022.90C

Atom 12159 CD1 TRP B264-57.700-20.387-21.9431.0023.98C

Atom 12161 NE1 TRP B264-56.800-21.386-22.2141.0023.95N

Atom 12163 CE2 TRP B264-57.124-21.949-23.4171.0023.51C

Atom 12164 CD2 TRP B264-58.252-21.273-23.9151.0023.40C

Atom 12165 CE3 TRP B264-58.776-21.652-25.1471.0023.68C

Atom 12167 CZ3 TRP B264-58.178-22.669-25.8261.0024.44C

Atom 12169 CH2 TRP B264-57.060-23.324-25.3101.0024.97C

Atom 12171 CZ2 TRP B264-56.521-22.978-24.1031.0024.44C

Atom 12173C TRP B264-60.897-20.326-21.0501.0021.11C

Atom 12174O TRP B264-60.768-21.511-20.7481.0020.98O

Atom 12176N ALA B265-60.916-19.344-20.1471.0020.17N

Atom 12177 CA ALA B265-60.774-19.602-18.7121.0019.36C

Atom 12179 CB ALA B265-60.621-18.305-17.9441.0019.30C

Atom 12183C ALA B265-61.947-20.397-18.1711.0018.63C

Atom 12184O ALA B265-61.763-21.349-17.4341.0018.64O

Atom 12186N VAL B266-63.159-20.034-18.5571.0018.11N

Atom 12187 CA VAL B266-64.335-20.758-18.0751.0017.60C

Atom 12189 CB VAL B266-65.652-20.221-18.6751.0017.38C

Atom 12191 CG1 VAL B266-65.902-18.803-18.1991.0017.09C

Atom 12195 CG2 VAL B266-66.817-21.120-18.3121.0015.40C

Atoms 12199C VAL B266-64.221-22.246-18.3761.0017.67C

Atom 12200O VAL B266-64.766-23.058-17.6471.0018.27O

Atom 12202N GLY B267-63.516-22.607-19.4441.0017.43N

Atom 12203 CA GLY B267-63.316-24.013-19.7891.0016.98C

Atoms 12206C GLY B267-62.253-24.683-18.9471.0016.55C

Atom 12207O GLY B267-62.360-25.859-18.6091.0016.37O

Atom 12209N VAL B268-61.215-23.939-18.6081.0016.30N

Atom 12210 CA VAL B268-60.160-24.500-17.7941.0016.23C

Atom 12212 CB VAL B268-58.893-23.651-17.8401.0015.68C

Atom 12214 CG1 VAL B268-57.857-24.194-16.8941.0015.01C

Atom 12218 CG2 VAL B268-58.361-23.674-19.2351.0015.01C

Atom 12222C VAL B268-60.654-24.718-16.3741.0016.86C

Atoms 12223O VAL B268-60.421-25.784-15.8131.0016.93O

Atom 12225N ALA B269-61.362-23.733-15.8171.0017.64N

Atom 12226 CA ALA B269-61.911-23.838-14.4611.0018.46C

Atom 12228 CB ALA B269-60.958-23.215-13.4721.0018.15C

Atom 12232C ALA B269-63.312-23.213-14.3401.0019.34C

Atom 12233O ALA B269-63.448-22.030-14.0471.0019.78O

Atoms 12235N PHE B270-64.347-24.028-14.5291.0020.34N

Atom 12236 CA PHE B270-65.724-23.535-14.6311.0021.21C

Atom 12238 CB PHE B270-66.564-24.483-15.4821.0021.34C

Atom 12241 CG PHE B270-67.083-25.667-14.7181.0022.46C

Atoms 12242 CD1 PHE B270-68.294-25.596-14.0391.0023.19C

Atoms 12244 CE1 PHE B270-68.756-26.672-13.3151.0023.27C

Atom 12246 CZ PHE B270-68.003-27.836-13.2581.0023.35C

Atom 12248 CE2 PHE B270-66.794-27.918-13.9321.0022.73C

Atom 12250 CD2 PHE B270-66.340-26.843-14.6461.0022.88C

Atoms 12252C PHE B270-66.464-23.366-13.3161.0021.98C

Atom 12253O PHE B270-67.408-22.583-13.2681.0021.93O

Atoms 12255N GLU B271-66.102-24.126-12.2751.0023.01N

Atom 12256 CA GLU B271-66.929-24.142-11.0371.0023.99C

Atom 12258 CB GLU B271-66.679-25.353-10.1131.0024.25C

Atom 12261 CG GLU B271-65.286-25.877-10.0921.0026.22C

Atom 12264 CD GLU B271-65.013-26.914-11.1831.0029.01C

Atom 12265 OE1 GLU B271-65.563-28.032-11.0901.0031.36O

Atom 12266 OE2 GLU B271-64.232-26.622-12.1211.0030.98O

Atoms 12267C GLU B271-66.795-22.831-10.2811.0023.90C

Atom 12268O GLU B271-65.702-22.296-10.1811.0024.29O

Atom 12270N PRO B272-67.913-22.316-9.7451.0024.09N

Atom 12271 CA PRO B272-68.005-20.885-9.4281.0024.11C

Atom 12273 CB PRO B272-69.380-20.751-8.7511.0024.03C

Atom 12276 CG PRO B272-70.083-22.069-8.9971.0024.12C

Atom 12279 CD PRO B272-69.013-23.083-9.1321.0023.99C

Atom 12282C PRO B272-66.900-20.386-8.5011.0024.28C

Atom 12283O PRO B272-66.421-19.261-8.6761.0024.40O

Atom 12284N GLN B273-66.480-21.222-7.5471.0024.20N

Atom 12285 CA GLN B273-65.500-20.809-6.5511.0024.20C

Atom 12287 CB GLN B273-65.437-21.840-5.4261.0024.42C

Atom 12290 CG GLN B273-64.750-23.176-5.7751.0025.17C

Atom 12293 CD GLN B273-65.717-24.334-6.0071.0026.13C

Atom 12294 OE1 GLN B273-66.857-24.141-6.4531.0027.46O

Atom 12295 NE2 GLN B273-65.251-25.554-5.7211.0025.05N

Atoms 12298C GLN B273-64.086-20.546-7.0881.0024.27C

Atom 12299O GLN B273-63.221-20.151-6.3291.0024.32O

Atom 12301N TYR B274-63.842-20.759-8.3801.0024.59N

Atom 12302 CA TYR B274-62.509-20.551-8.9621.0024.85C

Atom 12304 CB TYR B274-62.129-21.724-9.8801.0024.62C

Atom 12307 CG TYR B274-62.009-23.054-9.1841.0024.35C

Atom 12308 CD1 TYR B274-61.395-23.169-7.9461.0024.62C

Atom 12310 CE1 TYR B274-61.280-24.391-7.3141.0025.10C

Atom 12312 CZ TYR B274-61.771-25.525-7.9201.0024.92C

Atom 12313 OH TYR B274-61.661-26.748-7.2991.0024.73O

Atom 12315 CE2 TYR B274-62.366-25.437-9.1501.0024.76C

Atom 12317 CD2 TYR B274-62.477-24.203-9.7791.0024.70C

Atom 12319C TYR B274-62.409-19.235-9.7451.0025.27C

Atom 12320O TYR B274-61.956-19.210-10.8951.0025.42O

Atom 12322N SER B275-62.808-18.134-9.1211.0025.40N

Atom 12323 CA SER B275-62.755-16.849-9.8021.0025.43C

Atom 12325 CB SER B275-63.615-15.814-9.0711.0025.53C

Atom 12328 OG SER B275-65.006-16.068-9.2911.0025.52O

Atom 12330C SER B275-61.300-16.403-9.9481.0025.36C

Atom 12331O SER B275-60.885-15.903-10.9961.0025.17O

Atom 12333N ASP B276-60.517-16.617-8.9011.0025.41N

Atom 12334 CA ASP B276-59.095-16.353-8.9791.0025.42C

Atom 12336 CB ASP B276-58.390-16.794-7.7121.0025.44C

Atom 12339 CG ASP B276-58.728-15.925-6.5581.0026.32C

Atom 12340 OD1 ASP B276-59.302-14.857-6.8181.0027.50O

Atom 12341 OD2 ASP B276-58.442-16.299-5.3981.0030.16O

Atom 12342C ASP B276-58.495-17.069-10.1571.0025.20C

Atom 12343O ASP B276-57.745-16.461-10.9291.0025.66O

Atom 12345N CYS B277-58.814-18.353-10.3051.0024.60N

Atom 12346 CA CYS B277-58.228-19.110-11.3911.0024.30C

Atom 12348 CB CYS B277-58.684-20.561-11.3921.0024.28C

Atom 12351 SG CYS B277-57.737-21.574-12.5691.0023.82S

Atom 12353C CYS B277-58.593-18.448-12.6981.0024.09C

Atom 12354O CYS B277-57.727-18.013-13.4501.0023.87O

Atom 12356N ARG B278-59.893-18.329-12.9331.0024.22N

Atom 12357 CA ARG B278-60.400-17.746-14.1711.0023.98C

Atom 12359 CB ARG B278-61.917-17.556-14.1231.0023.93C

Atom 12362 CG ARG B278-62.662-18.871-14.2831.0024.07C

Atom 12365 CD ARG B278-64.132-18.670-14.6071.0024.48C

Atom 12368 NE ARG B278-64.874-18.141-13.4721.0023.75N

Atom 12370 CZ ARG B278-65.254-18.856-12.4191.0023.72C

Atom 12371 NH1 ARG B278-64.973-20.149-12.3261.0022.86N

Atom 12374 NH2 ARG B278-65.927-18.262-11.4431.0025.08N

Atom 12377C ARG B278-59.701-16.453-14.4911.0023.56C

Atom 12378O ARG B278-59.296-16.265-15.6281.0023.87O

Atom 12380N ASN B279-59.512-15.593-13.4951.0023.24N

Atom 12381 CA ASN B279-58.854-14.301-13.7341.0023.48C

Atom 12383 CB ASN B279-59.055-13.340-12.5741.0024.05C

Atom 12386 CG ASN B279-60.510-13.017-12.3461.0026.58C

Atom 12387 OD1 ASN B279-61.378-13.310-13.1891.0028.96O

Atom 12388 ND2 ASN B279-60.799-12.416-11.1941.0030.30N

Atom 12391C ASN B279-57.376-14.404-14.0271.0022.58C

Atom 12392O ASN B279-56.903-13.749-14.9411.0022.73O

Atom 12394N SER B280-56.648-15.205-13.2511.0021.62N

Atom 12395 CA SER B280-55.243-15.483-13.5501.0020.73C

Atom 12397 CB SER B280-54.696-16.597-12.6591.0020.85C

Atom 12400 OG SER B280-53.805-16.099-11.6831.0021.55O

Atom 12402C SER B280-55.091-15.896-15.0041.0020.04C

Atom 12403O SER B280-54.293-15.312-15.7381.0019.87O

Atom 12405N VAL B281-55.875-16.893-15.4131.0019.24N

Atom 12406 CA VAL B281-55.720-17.491-16.7201.0018.77C

Atom 12408 CB VAL B281-56.482-18.834-16.8151.0018.74C

Atom 12410 CG1 VAL B281-56.467-19.404-18.2511.0018.34C

Atom 12414 CG2 VAL B281-55.863-19.844-15.8481.0018.13C

Atom 12418C VAL B281-56.142-16.486-17.7871.0018.89C

Atom 12419O VAL B281-55.483-16.364-18.8321.0018.75O

Atom 12421N ALA B282-57.210-15.739-17.5051.0018.85N

Atom 12422 CA ALA B282-57.709-14.723-18.4391.0018.80C

Atom 12424 CB ALA B282-59.051-14.191-17.9911.0018.32C

Atom 12428C ALA B282-56.718-13.576-18.6151.0018.94C

Atom 12429O ALA B282-56.582-13.021-19.7001.0019.16O

Atoms 12431N LYS B283-56.022-13.211-17.5531.0019.24N

Atom 12432 CA LYS B283-55.037-12.145-17.6581.0019.62C

Atom 12434 CB LYS B283-54.649-11.615-16.2761.0019.68C

Atom 12437 CG LYS B283-55.779-10.923-15.5181.0019.95C

Atom 12440 CD LYS B283-55.265-10.398-14.1961.0021.72C

Atom 12443 CE LYS B283-56.364-10.236-13.1641.0023.83C

Atoms 12446 NZ LYS B283-56.129-9.003-12.3511.0024.72N

Atom 12450C LYS B283-53.802-12.643-18.3961.0019.77C

Atom 12451O LYS B283-53.237-11.929-19.2081.0020.05O

Atom 12453N MET B284-53.387-13.871-18.1171.0019.88N

Atom 12454 CA MET B284-52.136-14.367-18.6521.0019.90C

Atom 12456 CB MET B284-51.719-15.676-17.9601.0020.08C

Atom 12459 CG MET B284-51.125-15.505-16.5601.0020.62C

Atom 12462 SD MET B284-49.782-14.295-16.4851.0023.69S

Atom 12463 CE MET B284-50.600-12.872-15.7541.0023.82C

Atom 12467C MET B284-52.257-14.572-20.1451.0019.82C

Atom 12468O MET B284-51.326-14.269-20.8891.0020.21O

Atom 12470N PHE B285-53.401-15.088-20.5791.0019.72N

Atom 12471 CA PHE B285-53.620-15.428-21.9861.0019.66C

Atom 12473 CB PHE B285-54.863-16.324-22.1141.0020.09C

Atom 12476 CG PHE B285-54.986-17.077-23.4271.0021.18C

Atom 12477 CD1 PHE B285-53.877-17.362-24.2321.0022.86C

Atom 12479 CE1 PHE B285-54.013-18.070-25.4241.0022.58C

Atom 12481 CZ PHE B285-55.254-18.518-25.8061.0023.49C

Atom 12483 CE2 PHE B285-56.365-18.254-25.0021.0023.36C

Atom 12485 CD2 PHE B285-56.222-17.551-23.8231.0021.76C

Atom 12487C PHE B285-53.781-14.148-22.7811.0019.18C

Atom 12488O PHE B285-53.333-14.046-23.9141.0018.98O

Atom 12490N SER B286-54.410-13.161-22.1641.0018.92N

Atom 12491 CA SER B286-54.488-11.843-22.7531.0019.15C

Atom 12493 CB SER B286-55.292-10.894-21.8631.0019.38C

Atom 12496 OG SER B286-56.684-11.180-21.9571.0020.24O

Atom 12498C SER B286-53.106-11.267-23.0321.0018.91C

Atom 12499O SER B286-52.894-10.668-24.0871.0019.48O

Atoms 12501N PHE B287-52.172-11.446-22.1021.0018.48N

Atom 12502 CA PHE B287-50.768-11.065-22.3391.0018.30C

Atom 12504 CB PHE B287-49.958-11.035-21.0441.0018.27C

Atom 12507 CG PHE B287-50.040-9.740-20.3241.0018.59C

Atoms 12508 CD1 PHE B287-49.375-8.624-20.8131.0020.02C

Atoms 12510 CE1 PHE B287-49.456-7.410-20.1521.0020.57C

Atom 12512 CZ PHE B287-50.208-7.308-18.9851.0020.02C

Atom 12514 CE2 PHE B287-50.869-8.417-18.5031.0019.78C

Atom 12516 CD2 PHE B287-50.781-9.623-19.1641.0019.05C

Atom 12518C PHE B287-50.067-11.978-23.3391.0018.01C

Atom 12519O PHE B287-49.374-11.498-24.2291.0018.00O

Atoms 12521N VAL B288-50.236-13.286-23.1941.0017.69N

Atom 12522 CA VAL B288-49.720-14.206-24.1971.0017.66C

Atoms 12524 CB VAL B288-50.168-15.649-23.9301.0017.37C

Atom 12526 CG1 VAL B288-49.937-16.529-25.1341.0016.24C

Atoms 12530 CG2 VAL B288-49.414-16.185-22.7581.0017.21C

Atoms 12534C VAL B288-50.081-13.761-25.6331.0018.08C

Atom 12535O VAL B288-49.207-13.710-26.4921.0018.08O

Atom 12537N THR B289-51.327-13.396-25.8951.0018.42N

Atom 12538 CA THR B289-51.683-13.001-27.2561.0019.33C

Atom 12540 CB THR B289-53.171-12.736-27.4011.0019.35C

Atom 12542 OG1 THR B289-53.573-11.895-26.3211.0021.59O

Atom 12544 CG2 THR B289-53.973-14.046-27.3501.0019.09C

Atom 12548C THR B289-50.901-11.766-27.7231.0019.71C

Atom 12549O THR B289-50.469-11.707-28.8911.0019.88O

Atom 12551N ILE B290-50.689-10.796-26.8291.0019.94N

Atom 12552 CA ILE B290-49.943-9.585-27.2251.0020.39C

Atom 12554 CB ILE B290-50.069-8.410-26.2211.0020.50C

Atom 12556 CG1 ILE B290-51.510-8.137-25.8231.0021.25C

Atom 12559 CD1 ILE B290-51.650-6.854-25.0021.0021.58C

Atom 12563 CG2 ILE B290-49.546-7.134-26.8531.0020.39C

Atom 12567C ILE B290-48.434-9.840-27.4381.0020.45C

Atom 12568O ILE B290-47.853-9.317-28.3931.0020.76O

Atom 12570N ILE B291-47.808-10.616-26.5461.0020.21N

Atom 12571 CA ILE B291-46.375-10.869-26.6181.0019.87C

Atom 12573 CB ILE B291-45.840-11.603-25.4071.0019.79C

Atom 12575 CG1 ILE B291-46.205-10.879-24.1021.0019.71C

Atom 12578 CD1 ILE B291-45.326-9.734-23.7481.0019.77C

Atom 12582 CG2 ILE B291-44.336-11.747-25.5161.0018.91C

Atom 12586C ILE B291-46.134-11.735-27.8251.0020.44C

Atom 12587O ILE B291-45.233-11.481-28.6001.0020.35O

Atom 12589N ASP B292-46.965-12.751-28.0051.0021.33N

Atom 12590 CA ASP B292-46.915-13.563-29.2281.0022.13C

Atom 12592 CB ASP B292-48.120-14.508-29.3161.0022.40C

Atom 12595 CG ASP B292-47.847-15.741-30.1601.0023.47C

Atom 12596 OD1 ASP B292-46.852-15.765-30.9231.0024.83O

Atom 12597 OD2 ASP B292-48.637-16.707-30.0381.0025.22O

Atom 12598C ASP B292-46.856-12.716-30.5071.0022.28C

Atom 12599O ASP B292-46.088-13.033-31.3991.0022.73O

Atom 12601N ASP B293-47.656-11.658-30.6111.0022.22N

Atom 12602 CA ASP B293-47.630-10.828-31.8221.0022.43C

Atom 12604 CB ASP B293-48.840-9.894-31.8851.0023.03C

Atom 12607 CG ASP B293-50.157-10.644-31.9591.0024.69C

Atom 12608 OD1 ASP B293-50.113-11.900-32.0251.0028.66O

Atom 12609 OD2 ASP B293-51.231-9.986-31.9301.0023.57O

Atom 12610C ASP B293-46.354-9.997-31.9211.0021.94C

Atom 12611O ASP B293-45.898-9.674-33.0191.0022.31O

Atom 12613N ILE B294-45.783-9.643-30.7801.0021.05N

Atom 12614 CA ILE B294-44.513-8.941-30.7701.0020.53C

Atoms 12616 CB ILE B294-44.166-8.448-29.3441.0020.42C

Atom 12618 CG1 ILE B294-45.150-7.349-28.9451.0019.66C

Atoms 12621 CD1 ILE B294-45.057-6.956-27.5361.0018.81C

Atom 12625 CG2 ILE B294-42.726-7.924-29.2531.0019.99C

Atom 12629C ILE B294-43.416-9.845-31.3431.0020.44C

Atom 12630O ILE B294-42.650-9.431-32.2051.0020.17O

Atom 12632N TYR B295-43.355-11.088-30.8861.0020.65N

Atom 12633 CA TYR B295-42.313-12.008-31.3531.0020.76C

Atom 12635 CB TYR B295-42.145-13.198-30.4121.0020.29C

Atom 12638 CG TYR B295-41.393-12.926-29.1291.0017.92C

Atom 12639 CD1 TYR B295-40.117-13.409-28.9361.0017.62C

Atom 12641 CE1 TYR B295-39.427-13.195-27.7471.0017.12C

Atom 12643 CZ TYR B295-40.022-12.493-26.7301.0016.61C

Atom 12644 OH TYR B295-39.357-12.281-25.5281.0014.46O

Atom 12646 CE2 TYR B295-41.296-12.008-26.9111.0016.82C

Atom 12648 CD2 TYR B295-41.972-12.235-28.1021.0016.39C

Atom 12650C TYR B295-42.619-12.519-32.7491.0021.65C

Atom 12651O TYR B295-41.698-12.751-33.5401.0022.13O

Atom 12653N ASP B296-43.905-12.677-33.0491.0022.47N

Atom 12654 CA ASP B296-44.327-13.316-34.2851.0023.52C

Atom 12656 CB ASP B296-45.761-13.851-34.1851.0023.99C

Atom 12659 CG ASP B296-46.134-14.744-35.3691.0026.22C

Atom 12660 OD1 ASP B296-45.508-15.832-35.5381.0027.70O

Atom 12661 OD2 ASP B296-47.052-14.348-36.1281.0028.78O

Atom 12662C ASP B296-44.228-12.392-35.4781.0023.68C

Atom 12663O ASP B296-43.673-12.784-36.5021.0024.01O

Atom 12665N VAL B297-44.765-11.178-35.3641.0023.90N

Atom 12666 CA VAL B297-44.801-10.273-36.5241.0023.99C

Atom 12668 CB VAL B297-46.251-10.003-36.9731.0023.87C

Atom 12670 CG1 VAL B297-46.949-11.310-37.1971.0023.75C

Atom 12674 CG2 VAL B297-47.002-9.136-35.9661.0023.05C

Atom 12678C VAL B297-44.060-8.940-36.3831.0024.27C

Atom 12679O VAL B297-43.485-8.465-37.3421.0023.84O

Atom 12681N TYR B298-44.058-8.347-35.1991.0024.87N

Atom 12682 CA TYR B298-43.760-6.926-35.0781.0025.67C

Atom 12684 CB TYR B298-44.656-6.294-34.0101.0026.06C

Atom 12687 CG TYR B298-44.520-4.789-33.9321.0027.95C

Atom 12688 CD1 TYR B298-45.097-3.968-34.9011.0029.74C

Atom 12690 CE1 TYR B298-44.982-2.574-34.8431.0029.93C

Atom 12692 CZ TYR B298-44.282-1.991-33.8061.0029.96C

Atom 12693 OH TYR B298-44.165-,. 631-33.7461.0030.01O

Atom 12695 CE2 TYR B298-43.697-2.777-32.8291.0030.39C

Atom 12697 CD2 TYR B298-43.811-4.181-32.8991.0029.96C

Atom 12699C TYR B298-42.318-6.592-34.7551.0025.76C

Atom 12700O TYR B298-41.696-5.830-35.4701.0026.54O

Atom 12702N GLY B299-41.798-7.111-33.6531.0025.89N

Atom 12703 CA GLY B299-40.473-6.706-33.1671.0025.78C

Atom 12706C GLY B299-39.346-7.341-33.9511.0025.52C

Atom 12707O GLY B299-39.513-8.410-34.5251.0026.04O

Atom 12709N THR B300-38.196-6.685-33.9901.0025.32N

Atom 12710 CA THR B300-37.063-7.237-34.7161.0025.16C

Atom 12712 CB THR B300-36.088-6.164-35.2951.0025.08C

Atom 12714 OG1 THR B300-35.191-5.710-34.2811.0025.07O

Atom 12716 CG2 THR B300-36.833-4.978-35.8751.0025.08C

Atom 12720C THR B300-36.324-8.139-33.7711.0025.13C

Atom 12721O THR B300-36.335-7.950-32.5701.0025.28O

Atoms 12723N LEU B301-35.662-9.129-34.3321.0025.50N

Atom 12724 CA LEU B301-34.918-10.093-33.5381.0025.42C

Atom 12726 CB LEU B301-34.148-11.020-34.4791.0025.17C

Atom 12729 CG LEU B301-33.624-12.338-33.9411.0024.95C

Atom 12731 CD1 LEU B301-34.715-13.233-33.4371.0024.42C

Atom 12735 CD2 LEU B301-32.900-12.998-35.0801.0026.50C

Atoms 12739C LEU B301-33.995-9.425-32.4851.0025.54C

Atoms 12740O LEU B301-33.843-9.959-31.3941.0025.35O

Atom 12742N ASP B302-33.417-8.257-32.7821.0025.68N

Atom 12743 CA ASP B302-32.598-7.550-31.7741.0026.02C

Atom 12745 CB ASP B302-31.800-6.377-32.3781.0026.37C

Atom 12748 CG ASP B302-30.563-6.833-33.1671.0028.27C

Atom 12749 OD1 ASP B302-29.508-6.156-33.0481.0029.05O

Atom 12750 OD2 ASP B302-30.652-7.852-33.9101.0031.04O

Atoms 12751C ASP B302-33.472-7.037-30.6301.0025.69C

Atom 12752O ASP B302-33.110-7.142-29.4471.0025.90O

Atom 12754N GLU B303-34.622-6.473-30.9931.0025.04N

Atom 12755 CA GLU B303-35.600-6.029-30.0111.0024.33C

Atom 12757 CB GLU B303-36.783-5.346-30.6971.0024.20C

Atom 12760 CG GLU B303-36.399-4.109-31.4661.0024.23C

Atom 12763 CD GLU B303-37.589-3.382-32.0631.0024.23C

Atom 12764 OE1 GLU B303-38.496-4.065-32.6041.0022.66O

Atom 12765 OE2 GLU B303-37.592-2.121-31.9951.0023.93O

Atoms 12766C GLU B303-36.103-7.212-29.1931.0023.87C

Atom 12767O GLU B303-36.396-7.058-28.0111.0023.59O

Atoms 12769N LEU B304-36.204-8.383-29.8251.0023.39N

Atom 12770 CA LEU B304-36.766-9.570-29.1661.0023.23C

Atom 12772 CB LEU B304-37.180-10.624-30.2081.0022.83C

Atom 12775 CG LEU B304-38.381-10.217-31.0741.0022.06C

Atoms 12777 CD1 LEU B304-38.822-11.321-32.0371.0020.11C

Atoms 12781 CD2 LEU B304-39.551-9.800-30.1631.0021.94C

Atoms 12785C LEU B304-35.810-10.147-28.1061.0023.37C

Atom 12786O LEU B304-36.248-10.785-27.1411.0023.22O

Atoms 12788N GLU B305-34.514-9.892-28.2831.0023.30N

Atom 12789 CA GLU B305-33.512-10.308-27.3241.0023.18C

Atom 12791 CB GLU B305-32.114-10.176-27.8991.0023.58C

Atom 12794 CG GLU B305-31.832-11.142-29.0471.0025.27C

Atom 12797 CD GLU B305-31.306-12.488-28.5851.0027.91C

Atom 12798 OE1 GLU B305-30.946-13.303-29.4701.0029.87O

Atoms 12799 OE2 GLU B305-31.244-12.728-27.3511.0029.28O

Atoms 12800C GLU B305-33.633-9.440-26.1041.0022.52C

Atom 12801O GLU B305-33.793-9.956-25.0051.0023.39O

Atom 12803N LEU B306-33.576-8.124-26.2741.0021.51N

Atom 12804 CA LEU B306-33.715-7.224-25.1141.0020.70C

Atom 12806 CB LEU B306-33.899-5.764-25.5441.0020.59C

Atom 12809 CG LEU B306-32.769-5.065-26.2931.0020.12C

Atom 12811 CD1 LEU B306-32.992-3.576-26.2031.0019.89C

Atom 12815 CD2 LEU B306-31.402-5.437-25.7391.0019.81C

Atoms 12819C LEU B306-34.896-7.645-24.2371.0019.91C

Atoms 12820O LEU B306-34.771-7.778-23.0311.0019.53O

Atom 12822N PHE B307-36.030-7.883-24.8721.0019.48N

Atom 12823 CA PHE B307-37.231-8.267-24.1701.0019.36C

Atom 12825 CB PHE B307-38.400-8.406-25.1381.0019.54C

Atom 12828 CG PHE B307-39.729-8.296-24.4821.0019.66C

Atom 12829 CD1 PHE B307-40.365-7.079-24.4001.0021.03C

Atom 12831 CE1 PHE B307-41.590-6.968-23.7871.0021.62C

Atom 12833 CZ PHE B307-42.182-8.072-23.2481.0020.25C

Atom 12835 CE2 PHE B307-41.553-9.292-23.3291.0020.07C

Atom 12837 CD2 PHE B307-40.338-9.400-23.9391.0019.62C

Atom 12839C PHE B307-37.039-9.577-23.4431.0019.22C

Atom 12840O PHE B307-37.354-9.684-22.2601.0019.50O

Atom 12842N THR B308-36.532-10.583-24.1431.0018.96N

Atom 12843 CA THR B308-36.321-11.874-23.5111.0018.84C

Atom 12845 CB THR B308-35.774-12.879-24.4901.0018.62C

Atom 12847 OG1 THR B308-36.687-12.988-25.5791.0018.88O

Atom 12849 CG2 THR B308-35.626-14.228-23.8331.0018.74C

Atom 12853C THR B308-35.384-11.737-22.3171.0019.04C

Atom 12854O THR B308-35.686-12.244-21.2331.0018.69O

Atoms 12856N ASP B309-34.264-11.031-22.5111.0019.36N

Atom 12857 CA ASP B309-33.335-10.751-21.4211.0019.65C

Atom 12859 CB ASP B309-32.121-9.983-21.9421.0019.92C

Atom 12862 CG ASP B309-31.171-9.536-20.8141.0023.51C

Atom 12863 OD1 ASP B309-30.520-10.412-20.1751.0027.27O

Atom 12864 OD2 ASP B309-31.076-8.299-20.5611.0027.40O

Atom 12865C ASP B309-34.048-9.977-20.2951.0019.08C

Atom 12866O ASP B309-33.912-10.308-19.1241.0018.55O

Atom 12868N ALA B310-34.836-8.975-20.6651.0018.93N

Atom 12869 CA ALA B310-35.546-8.151-19.6881.0019.12C

Atoms 12871 CB ALA B310-36.346-7.062-20.3801.0018.79C

Atom 12875C ALA B310-36.462-8.965-18.7841.0019.36C

Atom 12876O ALA B310-36.560-8.696-17.5771.0019.58O

Atom 12878N VAL B311-37.143-9.942-19.3701.0019.61N

Atom 12879 CA VAL B311-37.996-10.845-18.6111.0019.68C

Atom 12881 CB VAL B311-38.867-11.682-19.5551.0019.46C

Atom 12883 CG1 VAL B311-39.948-10.825-20.1231.0018.49C

Atom 12887 CG2 VAL B311-39.469-12.863-18.8431.0019.31C

Atom 12891C VAL B311-37.161-11.726-17.6731.0020.46C

Atom 12892O VAL B311-37.479-11.843-16.4941.0020.25O

Atoms 12894N GLU B312-36.085-12.317-18.1891.0021.67N

Atom 12895 CA GLU B312-35.198-13.168-17.3841.0022.65C

Atoms 12897 CB GLU B312-34.056-13.708-18.2391.0023.03C

Atom 12900 CG GLU B312-34.454-14.764-19.2611.0024.88C

Atom 12903 CD GLU B312-33.335-15.077-20.2671.0027.34C

Atom 12904 OE1 GLU B312-33.485-16.057-21.0281.0029.07O

Atom 12905 OE2 GLU B312-32.316-14.342-20.3131.0028.63O

Atom 12906C GLU B312-34.598-12.443-16.1671.0023.09C

Atom 12907O GLU B312-34.506-13.007-15.0821.0023.04O

Atom 12909N ARG B313-34.186-11.199-16.3351.0023.67N

Atom 12910 CA ARG B313-33.590-10.486-15.2221.0024.60C

Atom 12912 CB ARG B313-32.609-9.436-15.7351.0025.26C

Atom 12915 CG ARG B313-31.333-10.030-16.3981.0027.83C

Atom 12918 CD ARG B313-30.289-8.943-16.7541.0031.87C

Atom 12921 NE ARG B313-30.922-7.793-17.4301.0035.71N

Atom 12923 CZ ARG B313-31.341-6.661-16.8371.0038.42C

Atom 12924 NH1 ARG B313-31.189-6.452-15.5221.0039.15N

Atom 12927 NH2 ARG B313-31.919-5.711-17.5761.0039.25N

Atom 12930C ARG B313-34.638-9.879-14.2801.0024.67C

Atom 12931O ARG B313-34.359-9.645-13.1171.0024.09O

Atom 12933N TRP B314-35.843-9.635-14.7811.0025.60N

Atom 12934 CA TRP B314-36.971-9.180-13.9511.0026.20C

Atom 12936 CB TRP B314-37.488-10.339-13.0971.0025.90C

Atom 12939 CG TRP B314-38.912-10.184-12.6621.0023.93C

Atom 12940 CD1 TRP B314-39.355-9.854-11.4241.0022.76C

Atom 12942 NE1 TRP B314-40.727-9.804-11.4121.0021.93N

Atom 12944 CE2 TRP B314-41.189-10.107-12.6591.0020.38C

Atom 12945 CD2 TRP B314-40.074-10.352-13.4731.0021.17C

Atom 12946 CE3 TRP B314-40.277-10.684-14.8111.0020.19C

Atom 12948 CZ3 TRP B314-41.549-10.766-15.2801.0019.79C

Atom 12950 CH2 TRP B314-42.640-10.512-14.4451.0021.00C

Atom 12952 CZ2 TRP B314-42.474-10.179-13.1301.0020.60C

Atom 12954C TRP B314-36.620-7.966-13.0761.0027.57C

Atom 12955O TRP B314-36.890-7.935-11.8701.0027.56O

Atom 12957N ASP B315-36.039-6.959-13.7181.0029.12N

Atom 12958 CA ASP B315-35.452-5.822-13.0271.0030.46C

Atom 12960 CB ASP B315-33.935-5.796-13.3151.0030.84C

Atom 12963 CG ASP B315-33.227-4.551-12.7721.0032.75C

Atom 12964 OD1 ASP B315-33.747-3.904-11.8301.0035.67O

Atom 12965 OD2 ASP B315-32.128-4.222-13.2951.0034.91O

Atom 12966C ASP B315-36.157-4.592-13.5571.0031.10C

Atom 12967O ASP B315-35.888-4.157-14.6741.0031.35O

Atom 12969N VAL B316-37.088-4.044-12.7811.0032.06N

Atom 12970 CA VAL B316-37.864-2.896-13.2621.0032.65C

Atom 12972 CB VAL B316-39.016-2.510-12.3341.0032.45C

Atom 12974 CG1 VAL B316-39.911-1.499-13.0121.0032.15C

Atom 12978 CG2 VAL B316-38.490-1.960-11.0401.0032.91C

Atom 12982C VAL B316-36.964-1.692-13.4421.0033.43C

Atom 12983O VAL B316-37.228-; 854-14.2941.0033.74O

Atom 12985N ASN B317-35.881-1.628-12.6631.0034.29N

Atom 12986 CA ASN B317-34.937-., 510-12.7301.0034.63C

Atom 12988 CB ASN B317-33.995-., 526-11.5051.0034.50C

Atom 12991 CG ASN B317-34.692-., 084-10.2011.0034.08C

Atom 12992 OD1 ASN B317-35.1981.042-10.1041.0033.72O

Atom 12993 ND2 ASN B317-34.690-., 961-9.1931.0031.22N

Atom 12996C ASN B317-34.124-. 481-14.0291.0035.21C

Atom 12997O ASN B317-33.196.296-14.1271.0035.52O

Atom 12999N ALA B318-34.470-1.318-15.0131.0035.89N

Atom 13000 CA ALA B318-33.757-1.382-16.2991.0036.48C

Atom 13002 CB ALA B318-32.727-2.508-16.2531.0036.49C

Atom 13006C ALA B318-34.695-1.525-17.5341.0037.02C

Atom 13007O ALA B318-34.297-1.984-18.6161.0036.52O

Atom 13009N ILE B319-35.952-1.137-17.3391.0037.76N

Atom 13010 CA ILE B319-36.848-., 733-18.4241.0038.08C

Atom 13012 CB ILE B319-37.926.247-17.8931.0038.11C

Atom 13014 CG1 ILE B319-39.110-., 495-17.2931.0038.08C

Atom 13017 CD1 ILE B319-40.068.451-16.5961.0038.27C

Atom 13021 CG2 ILE B319-38.4081.189-18.9961.0037.84C

Atom 13025C ILE B319-36.134.053-19.5161.0038.29C

Atom 13026O ILE B319-36.192-., 324-20.6771.0038.68O

Atoms 13028N ASN B320-35.4601.141-19.1251.0038.36N

Atom 13029 CA ASN B320-34.9772.168-20.0741.0038.17C

Atoms 13031 CB ASN B320-34.2783.331-19.3311.0038.16C

Atom 13034 CG ASN B320-35.2584.207-18.5141.0037.87C

Atom 13035 OD1 ASN B320-36.3664.542-18.9551.0036.50O

Atom 13036 ND2 ASN B320-34.8274.589-17.3221.0038.12N

Atom 13039C ASN B320-34.0821.643-21.2061.0037.78C

Atoms 13040O ASN B320-33.8562.332-22.1811.0037.76O

Atom 13042N ASP B321-33.600.416-21.0831.0037.46N

Atom 13043 CA ASP B321-32.852-. 224-22.1621.0037.25C

Atoms 13045 CB ASP B321-32.091-1.467-21.6291.0037.83C

Atom 13048 CG ASP B321-31.351-1.207-20.2851.0039.33C

Atom 13049 OD1 ASP B321-31.247-. 021-19.8711.0040.72O

Atoms 13050 OD2 ASP B321-30.887-2.199-19.6481.0039.62O

Atom 13051C ASP B321-33.764-., 636-23.3391.0035.99C

Atom 13052O ASP B321-33.273-. 904-24.4361.0035.87O

Atoms 13054N LEU B322-35.076-., 674-23.1111.0034.66N

Atom 13055 CA LEU B322-36.024-1.263-24.0611.0033.77C

Atom 13057 CB LEU B322-37.180-1.961-23.3271.0033.65C

Atom 13060 CG LEU B322-36.994-3.260-22.5441.0032.41C

Atom 13062 CD1 LEU B322-38.223-3.482-21.6931.0031.54C

Atom 13066 CD2 LEU B322-36.769-4.432-23.4601.0030.73C

Atoms 13070C LEU B322-36.670-., 243-24.9821.0033.32C

Atom 13071O LEU B322-36.910.893-24.5701.0033.37O

Atoms 13073N PRO B323-37.005-. 667-26.2181.0032.72N

Atom 13074 CA PRO B323-37.856.068-27.1261.0032.42C

Atom 13076 CB PRO B323-38.239-., 985-28.1581.0032.28C

Atom 13079 CG PRO B323-37.098-1.849-28.2311.0032.46C

Atom 13082 CD PRO B323-36.498-1.891-26.8571.0032.79C

Atoms 13085C PRO B323-39.115.576-26.4531.0032.50C

Atom 13086O PRO B323-39.655-. 083-25.5501.0032.46O

Atom 13087N ASP B324-39.5901.725-26.9231.0032.44N

Atom 13088 CA ASP B324-40.7292.387-26.3181.0032.44C

Atom 13090 CB ASP B324-41.0593.678-27.0711.0032.91C

Atom 13093 CG ASP B324-40.2414.873-26.5761.0034.17C

Atom 13094 OD1 ASP B324-39.5074.728-25.5621.0035.83O

Atom 13095 OD2 ASP B324-40.3515.960-27.1961.0035.42O

Atom 13096C ASP B324-41.9671.504-26.1861.0031.78C

Atom 13097O ASP B324-42.5461.440-25.1021.0031.77O

Atom 13099N TYR B325-42.368.821-27.2581.0030.99N

Atom 13100 CA TYR B325-43.519-., 086-27.1671.0030.49C

Atom 13102 CB TYR B325-43.941-, 640-28.5361.0030.28C

Atom 13105 CG TYR B325-43.027-1.688-29.1341.0030.25C

Atom 13106 CD1 TYR B325-41.917-1.332-29.8931.0029.81C

Atom 13108 CE1 TYR B325-41.089-2.300-30.4491.0029.74C

Atom 13110 CZ TYR B325-41.371-3.643-30.2581.0030.22C

Atom 13111 OH TYR B325-40.565-4.625-30.8051.0031.28O

Atom 13113 CE2 TYR B325-42.466-4.015-29.5191.0030.23C

Atom 13115 CD2 TYR B325-43.288-3.038-28.9631.0030.49C

Atom 13117C TYR B325-43.284-1.221-26.1681.0030.14C

Atom 13118O TYR B325-44.219-1.638-25.4831.0030.19O

Atom 13120N MET B326-42.048-1.700-26.0601.0029.74N

Atom 13121 CA MET B326-41.755-2.820-25.1551.0029.82C

Atom 13123 CB MET B326-40.461-3.541-25.5491.0029.69C

Atom 13126 CG MET B326-40.650-4.510-26.6861.0028.83C

Atom 13129 SD MET B326-39.123-5.272-27.2041.0026.99S

Atom 13130 CE MET B326-39.761-6.499-28.3281.0029.13C

Atom 13134C MET B326-41.696-2.402-23.6831.0029.92C

Atom 13135O MET B326-42.032-3.204-22.8011.0029.75O

Atom 13137N LYS B327-41.251-1.166-23.4291.0029.68N

Atom 13138 CA LYS B327-41.318-., 578-22.0881.0029.46C

Atom 13140 CB LYS B327-41.016.921-22.1141.0029.93C

Atom 13143 CG LYS B327-39.5721.305-21.9511.0031.63C

Atom 13146 CD LYS B327-39.4102.803-22.2491.0034.93C

Atom 13149 CE LYS B327-37.9863.291-22.0211.0036.86C

Atom 13152 NZ LYS B327-37.6424.436-22.9171.0037.83N

Atoms 13156C LYS B327-42.708-., 752-21.5311.0028.46C

Atom 13157O LYS B327-42.879-1.314-20.4611.0028.54O

Atom 13159N LEU B328-43.696-., 258-22.2681.0027.39N

Atom 13160 CA LEU B328-45.056-., 216-21.7851.0026.79C

Atom 13162 CB LEU B328-45.946.519-22.7731.0026.68C

Atom 13165 CG LEU B328-47.2651.034-22.2121.0026.00C

Atom 13167 CD1 LEU B328-47.0101.964-21.0361.0024.88C

Atom 13171 CD2 LEU B328-48.0511.740-23.3081.0024.55C

Atoms 13175C LEU B328-45.560-1.628-21.5871.0026.70C

Atom 13176O LEU B328-46.110-1.983-20.5431.0027.03O

Atom 13178N CYS B329-45.341-2.453-22.5911.0026.39N

Atom 13179 CA CYS B329-45.750-3.843-22.5241.0026.12C

Atom 13181 CB CYS B329-45.382-4.526-23.8381.0026.47C

Atom 13184 SG CYS B329-45.857-6.236-23.8801.0030.60S

Atom 13186C CYS B329-45.124-4.568-21.3191.0024.45C

Atom 13187O CYS B329-45.829-5.105-20.4861.0023.93O

Atom 13189N PHE B330-43.801-4.553-21.2281.0023.30N

Atom 13190 CA PHE B330-43.087-5.220-20.1411.0022.47C

Atom 13192 CB PHE B330-41.575-5.019-20.2671.0022.42C

Atom 13195 CG PHE B330-40.800-5.518-19.0761.0022.37C

Atom 13196 CD1 PHE B330-40.502-6.864-18.9401.0022.47C

Atom 13198 CE1 PHE B330-39.799-7.339-17.8361.0021.64C

Atom 13200 CZ PHE B330-39.379-6.472-16.8661.0021.50C

Atom 13202 CE2 PHE B330-39.659-5.122-16.9831.0021.92C

Atom 13204 CD2 PHE B330-40.374-4.648-18.0841.0022.29C

Atom 13206C PHE B330-43.524-4.739-18.7651.0021.87C

Atom 13207O PHE B330-43.779-5.552-17.8751.0021.98O

Atom 13209N LEU B331-43.594-3.427-18.5731.0020.88N

Atom 13210 CA LEU B331-43.997-2.894-17.2761.0020.25C

Atom 13212 CB LEU B331-43.927-1.354-17.2571.0020.06C

Atom 13215 CG LEU B331-44.124-. 628-15.9121.0019.21C

Atom 13217 CD1 LEU B331-43.542-1.408-14.7371.0018.78C

Atom 13221 CD2 LEU B331-43.555.770-15.9571.0015.75C

Atoms 13225C LEU B331-45.398-3.408-16.9021.0019.99C

Atom 13226O LEU B331-45.606-3.860-15.7711.0019.67O

Atom 13228N ALA B332-46.336-3.373-17.8601.0019.56N

Atom 13229 CA ALA B332-47.695-3.882-17.6291.0019.24C

Atom 13231 CB ALA B332-48.528-3.802-18.8911.0018.58C

Atom 13235C ALA B332-47.637-5.321-17.1081.0019.23C

Atom 13236O ALA B332-48.235-5.650-16.0791.0019.18O

Atoms 13238N LEU B333-46.891-6.162-17.8161.0019.16N

Atom 13239 CA LEU B333-46.727-7.554-17.4381.0019.08C

Atom 13241 CB LEU B333-45.830-8.260-18.4621.0018.97C

Atom 13244 CG LEU B333-45.511-9.758-18.3071.0019.18C

Atom 13246 CD1 LEU B333-46.779-10.611-18.1211.0018.09C

Atom 13250 CD2 LEU B333-44.676-10.262-19.4991.0017.17C

Atoms 13254C LEU B333-46.111-7.616-16.0421.0019.16C

Atom 13255O LEU B333-46.629-8.279-15.1371.0018.97O

Atom 13257N TYR B334-45.013-6.887-15.8841.0019.23N

Atom 13258 CA TYR B334-44.212-6.906-14.6641.0019.33C

Atom 13260 CB TYR B334-43.092-5.873-14.7851.0019.43C

Atom 13263 CG TYR B334-42.190-5.748-13.5961.0019.44C

Atom 13264 CD1 TYR B334-41.006-6.464-13.5241.0020.60C

Atom 13266 CE1 TYR B334-40.148-6.347-12.4421.0020.77C

Atom 13268 CZ TYR B334-40.474-5.503-11.4171.0021.51C

Atom 13269 OH TYR B334-39.628-5.387-10.3531.0021.42O

Atom 13271 CE2 TYR B334-41.646-4.768-11.4661.0022.15C

Atom 13273 CD2 TYR B334-42.495-4.892-12.5651.0020.55C

Atom 13275C TYR B334-45.065-6.614-13.4431.0019.37C

Atom 13276O TYR B334-44.980-7.337-12.4411.0019.94O

Atoms 13278N ASN B335-45.888-5.565-13.5271.0018.83N

Atom 13279 CA ASN B335-46.784-5.236-12.4431.0018.37C

Atom 13281 CB ASN B335-47.452-3.896-12.6751.0018.52C

Atom 13284 CG ASN B335-46.493-2.742-12.5181.0019.27C

Atom 13285 OD1 ASN B335-45.421-2.906-11.9531.0021.25O

Atom 13286 ND2 ASN B335-46.872-1.566-13.0221.0019.24N

Atoms 13289C ASN B335-47.812-6.333-12.2911.0018.22C

Atom 13290O ASN B335-47.966-6.891-11.2071.0018.53O

Atom 13292N THR B336-48.481-6.697-13.3791.0017.95N

Atom 13293 CA THR B336-49.525-7.728-13.3011.0017.61C

Atom 13295 CB THR B336-49.980-8.204-14.6761.0017.36C

Atom 13297 OG1 THR B336-50.249-7.065-15.5001.0017.02O

Atom 13299 CG2 THR B336-51.228-9.044-14.5511.0016.07C

Atom 13303C THR B336-49.065-8.941-12.5011.0017.75C

Atom 13304O THR B336-49.788-9.429-11.6211.0018.09O

Atom 13306N ILE B337-47.859-9.411-12.7851.0017.69N

Atom 13307 CA ILE B337-47.384-10.630-12.1651.0017.74C

Atom 13309 CB ILE B337-46.228-11.245-12.9491.0017.40C

Atom 13311 CG1 ILE B337-46.795-11.865-14.2271.0018.44C

Atom 13314 CD1 ILE B337-45.767-12.192-15.3001.0019.26C

Atom 13318 CG2 ILE B337-45.568-12.320-12.1521.0016.25C

Atom 13322C ILE B337-47.053-10.395-10.6991.0018.32C

Atom 13323O ILE B337-47.497-11.175-9.8381.0018.06O

Atom 13325N ASN B338-46.321-9.311-10.4041.0018.89N

Atom 13326 CA ASN B338-45.985-8.978-9.0071.0019.49C

Atom 13328 CB ASN B338-45.189-7.690-8.9171.0019.43C

Atom 13331 CG ASN B338-43.789-7.836-9.4441.0020.83C

Atom 13332 OD1 ASN B338-43.292-8.954-9.6341.0021.52O

Atom 13333 ND2 ASN B338-43.124-6.697-9.6761.0022.32N

Atom 13336C ASN B338-47.229-8.835-8.1461.0020.05C

Atom 13337O ASN B338-47.182-9.055-6.9531.0019.81O

Atoms 13339N GLU B339-48.337-8.459-8.7701.0020.81N

Atom 13340 CA GLU B339-49.589-8.347-8.0861.0021.81C

Atom 13342 CB GLU B339-50.563-7.544-8.9331.0022.69C

Atom 13345 CG GLU B339-51.240-6.422-8.1481.0027.28C

Atom 13348 CD GLU B339-52.571-5.959-8.7681.0032.79C

Atom 13349 OE1 GLU B339-52.761-4.713-8.8971.0036.20O

Atom 13350 OE2 GLU B339-53.416-6.837-9.1141.0034.35O

Atoms 13351C GLU B339-50.170-9.732-7.7621.0021.59C

Atom 13352O GLU B339-50.690-9.946-6.6661.0021.38O

Atom 13354N ILE B340-50.094-10.676-8.7001.0021.48N

Atom 13355 CA ILE B340-50.486-12.049-8.3841.0021.27C

Atom 13357 CB ILE B340-50.437-12.990-9.6031.0021.17C

Atom 13359 CG1 ILE B340-51.478-12.589-10.6431.0020.99C

Atom 13362 CD1 ILE B340-51.245-13.202-12.0171.0019.72C

Atom 13366 CG2 ILE B340-50.702-14.444-9.1771.0021.09C

Atom 13370C ILE B340-49.557-12.585-7.2781.0021.40C

Atom 13371O ILE B340-50.023-13.238-6.3341.0021.74O

Atom 13373N ALA B341-48.256-12.301-7.3801.0020.90N

Atom 13374 CA ALA B341-47.312-12.721-6.3491.0020.62C

Atom 13376 CB ALA B341-45.922-12.260-6.6941.0020.53C

Atom 13380C ALA B341-47.720-12.195-4.9691.0020.59C

Atom 13381O ALA B341-47.606-12.901-3.9501.0020.57O

Atom 13383N TYR B342-48.208-10.958-4.9491.0020.62N

Atom 13384 CA TYR B342-48.600-10.303-3.7071.0020.59C

Atom 13386 CB TYR B342-48.790-8.792-3.9071.0020.05C

Atom 13389 CG TYR B342-49.309-8.143-2.6741.0018.29C

Atom 13390 CD1 TYR B342-48.443-7.683-1.6981.0017.62C

Atom 13392 CE1 TYR B342-48.914-7.111-., 5181.0017.91C

Atom 13394 CZ TYR B342-50.285-7.005-. 2981.0018.18C

Atom 13395 OH TYR B342-50.763-6.433.8771.0016.00O

Atom 13397 CE2 TYR B342-51.169-7.467-1.2751.0018.10C

Atom 13399 CD2 TYR B342-50.670-8.037-2.4501.0017.67C

Atom 13401C TYR B342-49.863-10.928-3.1181.0021.48C

Atom 13402O TYR B342-49.960-11.089-1.9131.0020.91O

Atom 13404N ASP B343-50.832-11.273-3.9591.0022.93N

Atom 13405 CA ASP B343-52.048-11.925-3.4701.0024.30C

Atom 13407 CB ASP B343-53.010-12.282-4.6081.0024.59C

Atom 13410 CG ASP B343-53.577-11.060-5.3341.0026.66C

Atom 13411 OD1 ASP B343-53.619-9.936-4.7561.0028.24O

Atom 13412 OD2 ASP B343-54.004-11.247-6.5061.0029.56O

Atoms 13413C ASP B343-51.660-13.208-2.7611.0024.97C

Atom 13414O ASP B343-52.128-13.495-1.6581.0024.95O

Atoms 13416N ASN B344-50.792-13.973-3.4131.0025.90N

Atom 13417 CA ASN B344-50.322-15.252-2.8841.0026.59C

Atom 13419 CB ASN B344-49.623-16.043-3.9781.0026.74C

Atom 13422 CG ASN B344-50.594-16.639-4.9331.0028.21C

Atom 13423 OD1 ASN B344-51.080-17.737-4.6881.0032.10O

Atom 13424 ND2 ASN B344-50.923-15.916-6.0161.0028.40N

Atoms 13427C ASN B344-49.421-15.146-1.6551.0026.78C

Atom 13428O ASN B344-49.424-16.053-., 8211.0027.06O

Atoms 13430N LEU B345-48.647-14.067-1.5331.0026.74N

Atoms 13431 CA LEU B345-47.970-13.793-. 2611.0026.59C

Atoms 13433 CB LEU B345-47.005-12.618-., 3961.0026.25C

Atom 13436 CG LEU B345-46.046-12.376.7641.0024.65C

Atoms 13438 CD1 LEU B345-45.258-13.6211.1151.0022.50C

Atom 13442 CD2 LEU B345-45.119-11.251.3871.0023.54C

Atoms 13446C LEU B345-49.004-13.503.8401.0027.00C

Atom 13447O LEU B345-48.903-14.0141.9471.0026.93O

Atom 13449N LYS B346-50.008-12.697.5181.0027.54N

Atom 13450 CA LYS B346-51.012-12.3001.4911.0027.96C

Atom 13452 CB LYS B346-51.998-11.288.8891.0028.13C

Atom 13455 CG LYS B346-52.822-10.5271.9261.0028.70C

Atom 13458 CD LYS B346-53.781-9.5261.2811.0029.73C

Atom 13461 CE LYS B346-55.205-10.0631.1331.0031.17C

Atom 13464 NZ LYS B346-55.839-9.661-. 1711.0032.83N

Atom 13468C LYS B346-51.788-13.4981.9841.0028.31C

Atom 13469O LYS B346-52.074-13.6003.1771.0028.52O

Atom 13471N ASP B347-52.149-14.3961.0751.0028.56N

Atom 13472 CA ASP B347-53.102-15.4411.4271.0029.11C

Atoms 13474 CB ASP B347-54.068-15.736.2681.0029.50C

Atom 13477 CG ASP B347-54.902-14.500-. 1501.0031.04C

Atom 13478 OD1 ASP B347-54.961-13.500.6161.0031.35O

Atom 13479 OD2 ASP B347-55.496-14.534-1.2611.0033.39O

Atoms 13480C ASP B347-52.403-16.6991.8911.0028.79C

Atom 13481O ASP B347-52.824-17.3212.8541.0029.02O

Atom 13483N LYS B348-51.326-17.0681.2221.0028.74N

Atom 13484 CA LYS B348-50.612-18.2931.5641.0028.84C

Atom 13486 CB LYS B348-50.290-19.101.2991.0029.24C

Atom 13489 CG LYS B348-51.513-19.470-. 5761.0030.97C

Atom 13492 CD LYS B348-51.051-20.300-1.8031.0033.66C

Atom 13495 CE LYS B348-52.033-20.244-2.9891.0034.52C

Atoms 13498 NZ LYS B348-53.445-20.542-2.6071.0035.61N

Atom 13502C LYS B348-49.330-18.0292.3581.0027.97C

Atom 13503O LYS B348-48.763-18.9482.9251.0027.88O

Atom 13505N GLY B349-48.874-16.7852.4031.0027.21N

Atom 13506 CA GLY B349-47.625-16.4733.0751.0026.87C

Atom 13509C GLY B349-46.437-17.2272.5141.0026.71C

Atom 13510O GLY B349-45.576-17.6693.2711.0026.65O

Atom 13512N GLU B350-46.409-17.3901.1911.0026.61N

Atom 13513 CA GLU B350-45.263-17.953.4701.0026.43C

Atom 13515 CB GLU B350-45.624-19.310-1281.0026.85C

Atom 13518 CG GLU B350-45.685-20.453.8881.0029.63C

Atom 13521 CD GLU B350-44.304-21.0361.2271.0034.21C

Atom 13522 OE1 GLU B350-43.417-21.045.3281.0036.93O

Atom 13523 OE2 GLU B350-44.106-21.4982.3841.0035.89O

Atom 13524C GLU B350-44.900-16.981-. 6371.0025.49C

Atom 13525O GLU B350-45.774-16.312-1.1811.0025.35O

Atom 13527N ASN B351-43.616-16.866-. 9551.0024.74N

Atom 13528 CA ASN B351-43.206-16.046-2.0901.0024.47C

Atom 13530 CB ASN B351-41.851-15.369-1.8671.0024.94C

Atom 13533 CG ASN B351-41.428-14.489-3.0621.0026.98C

Atom 13534 OD1 ASN B351-41.976-14.605-4.1701.0028.96O

Atom 13535 ND2 ASN B351-40.457-13.601-2.8341.0029.55N

Atom 13538C ASN B351-43.095-16.918-3.3031.0023.33C

Atom 13539O ASN B351-42.120-17.641-3.4291.0023.47O

Atom 13541N ILE B352-44.060-16.823-4.2081.0022.09N

Atom 13542 CA ILE B352-44.048-17.644-5.4101.0021.22C

Atom 13544 CB ILE B352-45.452-18.213-5.6751.0021.23C

Atom 13546 CG1 ILE B352-46.464-17.080-5.9131.0021.11C

Atom 13549 CD1 ILE B352-47.346-17.305-7.1261.0020.33C

Atom 13553 CG2 ILE B352-45.875-19.116-4.5191.0019.79C

Atom 13557C ILE B352-43.508-16.947-6.6891.0020.88C

Atom 13558O ILE B352-43.486-17.553-7.7581.0020.76O

Atom 13560N LEU B353-43.030-15.705-6.5741.0020.44N

Atom 13561 CA LEU B353-42.603-14.907-7.7501.0019.84C

Atoms 13563 CB LEU B353-42.055-13.527-7.3251.0019.67C

Atoms 13566 CG LEU B353-42.003-12.339-8.3111.0018.47C

Atom 13568 CD1 LEU B353-43.306-12.083-9.0081.0017.03C

Atom 13572 CD2 LEU B353-41.604-11.064-7.5971.0017.08C

Atom 13576C LEU B353-41.587-15.628-8.6331.0019.81C

Atom 13577O LEU B353-41.720-15.596-9.8511.0019.55O

Atom 13579N PRO B354-40.578-16.299-8.0241.0020.01N

Atom 13580 CA PRO B354-39.571-17.010-8.8221.0019.73C

Atom 13582 CB PRO B354-38.781-17.796-7.7791.0019.55C

Atom 13585 CG PRO B354-38.928-17.037-6.5421.0019.61C

Atom 13588 CD PRO B354-40.289-16.413-6.5781.0019.90C

Atoms 13591C PRO B354-40.187-17.971-9.8041.0019.87C

Atom 13592O PRO B354-39.693-18.103-10.9181.0020.08O

Atom 13593N TYR B355-41.264-18.636-9.3871.0020.14N

Atom 13594 CA TYR B355-41.909-19.665-10.2161.0020.24C

Atom 13596 CB TYR B355-42.878-20.520-9.3941.0020.40C

Atom 13599 CG TYR B355-42.189-21.153-8.2141.0021.82C

Atom 13600 CD1 TYR B355-41.119-21.999-8.4121.0022.86C

Atom 13602 CE1 TYR B355-40.457-22.564-7.3531.0025.07C

Atom 13604 CZ TYR B355-40.850-22.285-6.0531.0025.58C

Atom 13605 OH TYR B355-40.153-22.887-5.0201.0027.33O

Atom 13607 CE2 TYR B355-41.918-21.433-5.8151.0023.93C

Atom 13609 CD2 TYR B355-42.577-20.867-6.9001.0023.10C

Atom 13611C TYR B355-42.625-19.001-11.3611.0019.67C

Atom 13612O TYR B355-42.455-19.405-12.5101.0019.75O

Atom 13614N LEU B356-43.385-17.954-11.0301.0018.97N

Atom 13615 CA LEU B356-44.180-17.205-12.0041.0018.26C

Atom 13617 CB LEU B356-45.039-16.157-11.2931.0018.03C

Atom 13620 CG LEU B356-46.056-16.727-10.3121.0018.13C

Atom 13622 CD1 LEU B356-46.691-15.613-9.5001.0019.37C

Atom 13626 CD2 LEU B356-47.106-17.521-11.0461.0017.93C

Atom 13630C LEU B356-43.298-16.536-13.0561.0017.76C

Atom 13631O LEU B356-43.598-16.567-14.2591.0016.93O

Atom 13633N THR B357-42.201-15.949-12.6001.0017.56N

Atom 13634 CA THR B357-41.335-15.215-13.5011.0017.63C

Atom 13636 CB THR B357-40.438-14.236-12.7591.0017.69C

Atom 13638 OG1 THR B357-39.530-14.974-11.9341.0018.39O

Atom 13640 CG2 THR B357-41.288-13.242-11.9271.0016.47C

Atom 13644C THR B357-40.477-16.145-14.3561.0017.55C

Atom 13645O THR B357-40.154-15.793-15.4981.0017.17O

Atoms 13647N LYS B358-40.127-17.321-13.8241.0017.37N

Atom 13648 CA LYS B358-39.462-18.337-14.6491.0017.55C

Atom 13650 CB LYS B358-39.030-19.542-13.8271.0017.87C

Atom 13653 CG LYS B358-38.450-20.718-14.6401.0018.75C

Atom 13656 CD LYS B358-37.013-20.497-15.1121.0020.18C

Atom 13659 CE LYS B358-36.361-21.843-15.4571.0021.49C

Atom 13662 NZ LYS B358-35.189-21.702-16.3611.0022.89N

Atom 13666C LYS B358-40.403-18.777-15.7541.0017.43C

Atom 13667O LYS B358-40.031-18.775-16.9261.0017.52O

Atom 13669N ALA B359-41.633-19.120-15.3841.0017.42N

Atom 13670 CA ALA B359-42.654-19.471-16.3591.0017.52C

Atom 13672 CB ALA B359-44.011-19.434-15.7381.0017.16C

Atom 13676C ALA B359-42.585-18.521-17.5311.0018.18C

Atom 13677O ALA B359-42.513-18.956-18.6751.0018.50O

Atom 13679N TRP B360-42.556-17.223-17.2451.0019.14N

Atom 13680 CA TRP B360-42.526-16.206-18.3011.0019.77C

Atom 13682 CB TRP B360-42.922-14.837-17.7461.0020.15C

Atom 13685 CG TRP B360-44.377-14.653-17.8131.0020.50C

Atom 13686 CD1 TRP B360-45.259-14.729-16.7881.0022.15C

Atom 13688 NE1 TRP B360-46.536-14.533-17.2481.0022.84N

Atom 13690 CE2 TRP B360-46.487-14.348-18.6031.0021.68C

Atom 13691 CD2 TRP B360-45.134-14.418-18.9871.0020.85C

Atom 13692 CE3 TRP B360-44.802-14.253-20.3341.0021.21C

Atom 13694 CZ3 TRP B360-45.821-14.025-21.2451.0020.75C

Atom 13696 CH2 TRP B360-47.166-13.961-20.8271.0021.21C

Atom 13698 CZ2 TRP B360-47.515-14.123-19.5161.0020.97C

Atom 13700C TRP B360-41.215-16.110-19.0811.0019.96C

Atom 13701O TRP B360-41.242-15.791-20.2711.0019.94O

Atom 13703N ALA B361-40.089-16.368-18.4201.0020.14N

Atom 13704 CA ALA B361-38.790-16.437-19.1021.0020.41C

Atom 13706 CB ALA B361-37.676-16.581-18.1021.0020.67C

Atom 13710C ALA B361-38.763-17.618-20.0411.0020.55C

Atom 13711O ALA B361-38.330-17.510-21.1871.0020.76O

Atom 13713N ASP B362-39.230-18.749-19.5341.0020.57N

Atoms 13714 CA ASP B362-39.360-19.965-20.3261.0020.97C

Atom 13716 CB ASP B362-39.984-21.082-19.4701.0021.39C

Atom 13719 CG ASP B362-38.938-21.902-18.6931.0022.80C

Atom 13720 OD1 ASP B362-38.836-23.109-18.9701.0028.57O

Atom 13721 OD2 ASP B362-38.210-21.384-17.8251.0022.78O

Atom 13722C ASP B362-40.179-19.748-21.6181.0020.66C

Atom 13723O ASP B362-39.740-20.141-22.7011.0020.69O

Atom 13725N LEU B363-41.346-19.110-21.5011.0020.22N

Atom 13726 CA LEU B363-42.245-18.885-22.6481.0019.82C

Atom 13728 CB LEU B363-43.592-18.327-22.1641.0019.11C

Atom 13731 CG LEU B363-44.644-17.945-23.2091.0017.02C

Atom 13733 CD1 LEU B363-44.829-19.033-24.2141.0016.20C

Atom 13737 CD2 LEU B363-45.979-17.618-22.5861.0014.21C

Atom 13741C LEU B363-41.633-17.950-23.7061.0020.76C

Atom 13742O LEU B363-41.656-18.235-24.9101.0021.00O

Atom 13744N CYS B364-41.088-16.826-23.2531.0021.42N

Atom 13745 CA CYS B364-40.427-15.884-24.1471.0021.67C

Atom 13747 CB CYS B364-39.969-14.639-23.3761.0021.86C

Atom 13750 SG CYS B364-41.327-13.638-22.7221.0023.36S

Atom 13752C CYS B364-39.229-16.547-24.8351.0021.52C

Atom 13753O CYS B364-39.010-16.323-26.0371.0021.67O

Atom 13755N ASN B365-38.454-17.352-24.0951.0020.83N

Atom 13756 CA ASN B365-37.306-18.025-24.7131.0020.65C

Atom 13758 CB ASN B365-36.425-18.756-23.6911.0020.74C

Atom 13761 CG ASN B365-35.330-17.865-23.1001.0020.53C

Atom 13762 OD1 ASN B365-34.553-17.229-23.8301.0018.26O

Atom 13763 ND2 ASN B365-35.252-17.841-21.7631.0020.69N

Atoms 13766C ASN B365-37.756-18.987-25.8111.0020.43C

Atom 13767O ASN B365-36.998-19.253-26.7591.0020.11O

Atom 13769N ALA B366-38.987-19.492-25.6671.0020.01N

Atom 13770 CA ALA B366-39.618-20.340-26.6651.0019.70C

Atom 13772 CB ALA B366-40.766-21.113-26.0451.0019.53C

Atom 13776C ALA B366-40.099-19.494-27.8381.0019.74C

Atom 13777O ALA B366-39.846-19.824-28.9891.0019.61O

Atoms 13779N PHE B367-40.791-18.399-27.5531.0019.99N

Atom 13780 CA PHE B367-41.138-17.446-28.6061.0020.36C

Atom 13782 CB PHE B367-41.805-16.194-28.0261.0020.62C

Atom 13785 CG PHE B367-43.200-16.403-27.5371.0021.75C

Atom 13786 CD1 PHE B367-44.136-17.071-28.3151.0023.00C

Atom 13788 CE1 PHE B367-45.435-17.242-27.8741.0023.60C

Atom 13790 CZ PHE B367-45.819-16.731-26.6481.0023.64C

Atom 13792 CE2 PHE B367-44.901-16.049-25.8711.0023.56C

Atom 13794 CD2 PHE B367-43.599-15.883-26.3161.0022.91C

Atoms 13796C PHE B367-39.906-16.986-29.3931.0020.19C

Atom 13797O PHE B367-39.934-16.903-30.6151.0019.98O

Atom 13799N LEU B368-38.839-16.659-28.6751.0020.24N

Atom 13800 CA LEU B368-37.629-16.161-29.2981.0020.31C

Atoms 13802 CB LEU B368-36.569-15.900-28.2321.0020.27C

Atom 13805 CG LEU B368-35.235-15.313-28.6941.0020.12C

Atom 13807 CD1 LEU B368-35.417-14.069-29.5921.0020.05C

Atom 13811 CD2 LEU B368-34.409-14.987-27.4651.0018.60C

Atoms 13815C LEU B368-37.122-17.179-30.2951.0020.53C

Atom 13816O LEU B368-36.844-16.844-31.4461.0020.49O

Atom 13818N GLN B369-37.032-18.426-29.8321.0020.80N

Atom 13819 CA GLN B369-36.565-19.557-30.6381.0020.90C

Atom 13821 CB GLN B369-36.614-20.857-29.8151.0020.98C

Atom 13824 CG GLN B369-36.343-22.159-30.5761.0020.75C

Atom 13827 CD GLN B369-34.946-22.238-31.1261.0020.29C

Atoms 13828 OE1 GLN B369-34.718-21.984-32.3051.0020.17O

Atom 13829 NE2 GLN B369-33.996-22.581-30.2721.0020.33N

Atom 13832C GLN B369-37.365-19.718-31.9101.0021.04C

Atom 13833O GLN B369-36.803-20.097-32.9291.0020.82O

Atoms 13835N GLU B370-38.668-19.453-31.8631.0021.80N

Atom 13836 CA GLU B370-39.480-19.512-33.0871.0022.73C

Atom 13838 CB GLU B370-40.996-19.518-32.8011.0023.18C

Atom 13841 CG GLU B370-41.449-20.608-31.8091.0025.92C

Atom 13844 CD GLU B370-42.927-21.064-31.9571.0029.74C

Atom 13845 OE1 GLU B370-43.840-20.191-32.1011.0030.13O

Atom 13846 OE2 GLU B370-43.156-22.316-31.8921.0031.94O

Atoms 13847C GLU B370-39.079-18.358-34.0161.0022.62C

Atom 13848O GLU B370-38.933-18.565-35.2211.0022.53O

Atom 13850N ALA B371-38.864-17.166-33.4561.0022.65N

Atom 13851 CA ALA B371-38.427-16.023-34.2541.0022.95C

Atom 13853 CB ALA B371-38.375-14.753-33.4241.0022.97C

Atom 13857C ALA B371-37.070-16.296-34.8911.0023.13C

Atom 13858O ALA B371-36.900-16.063-36.0911.0023.38O

Atom 13860N LYS B372-36.113-16.804-34.1071.0023.15N

Atom 13861 CA LYS B372-34.776-17.102-34.6401.0023.10C

Atom 13863 CB LYS B372-33.808-17.633-33.5751.0022.85C

Atom 13866 CG LYS B372-33.414-16.616-32.5141.0024.28C

Atom 13869 CD LYS B372-31.973-16.806-31.9691.0026.34C

Atom 13872 CE LYS B372-31.919-17.407-30.5441.0027.84C

Atom 13875 NZ LYS B372-31.673-16.405-29.4581.0027.93N

Atom 13879C LYS B372-34.887-18.093-35.7901.0023.16C

Atom 13880O LYS B372-34.231-17.920-36.8041.0023.73O

Atom 13882N TRP B373-35.720-19.122-35.6581.0023.11N

Atom 13883 CA TRP B373-35.844-20.094-36.7421.0022.99C

Atom 13885 CB TRP B373-36.746-21.274-36.3701.0022.71C

Atom 13888 CG TRP B373-36.081-22.343-35.5621.0020.71C

Atom 13889 CD1 TRP B373-34.770-22.740-35.6231.0019.89C

Atom 13891 NE1 TRP B373-34.540-23.757-34.7341.0019.05N

Atom 13893 CE2 TRP B373-35.715-24.050-34.0901.0018.91C

Atom 13894 CD2 TRP B373-36.707-23.184-34.5991.0018.41C

Atom 13895 CE3 TRP B373-38.007-23.288-34.1051.0015.66C

Atom 13897 CZ3 TRP B373-38.271-24.216-33.1301.0015.41C

Atom 13899 CH2 TRP B373-37.276-25.069-32.6471.0016.33C

Atom 13901 CZ2 TRP B373-35.994-25.005-33.1121.0017.53C

Atom 13903C TRP B373-36.374-19.416-37.9911.0023.59C

Atom 13904O TRP B373-35.878-19.653-39.0961.0023.60O

Atom 13906N LEU B374-37.374-18.559-37.8011.0024.32N

Atom 13907 CA LEU B374-38.008-17.859-38.9151.0024.66C

Atom 13909 CB LEU B374-39.181-17.019-38.4281.0024.85C

Atom 13912 CG LEU B374-40.112-16.449-39.4961.0025.45C

Atom 13914 CD1 LEU B374-41.002-17.535-40.0701.0024.83C

Atom 13918 CD2 LEU B374-40.959-15.293-38.8851.0026.92C

Atom 13922C LEU B374-37.009-16.975-39.6181.0024.64C

Atom 13923O LEU B374-36.934-16.992-40.8301.0024.33O

Atom 13925N TYR B375-36.232-16.220-38.8501.0025.09N

Atom 13926 CA TYR B375-35.283-15.274-39.4331.0025.71C

Atom 13928 CB TYR B375-34.534-14.479-38.3491.0025.91C

Atom 13931 CG TYR B375-33.536-13.468-38.8921.0027.11C

Atom 13932 CD1 TYR B375-33.950-12.200-39.3051.0027.98C

Atom 13934 CE1 TYR B375-33.039-11.271-39.8111.0028.61C

Atom 13936 CZ TYR B375-31.693-11.605-39.9041.0029.13C

Atom 13937 OH TYR B375-30.790-10.685-40.3971.0029.83O

Atom 13939 CE2 TYR B375-31.256-12.863-39.5011.0028.79C

Atom 13941 CD2 TYR B375-32.177-13.783-38.9951.0028.03C

Atom 13943C TYR B375-34.305-16.036-40.3011.0025.64C

Atom 13944O TYR B375-34.201-15.788-41.5031.0025.74O

Atom 13946N ASN B376-33.635-17.000-39.6851.0025.73N

Atom 13947 CA ASN B376-32.599-17.777-40.3461.0025.78C

Atom 13949 CB ASN B376-31.739-18.497-39.3031.0025.73C

Atom 13952 CG ASN B376-31.155-17.565-38.2731.0025.13C

Atoms 13953 OD1 ASN B376-30.491-16.590-38.6011.0025.53O

Atom 13954 ND2 ASN B376-31.389-17.874-37.0131.0024.64N

Atom 13957C ASN B376-33.126-18.824-41.3321.0026.04C

Atom 13958O ASN B376-32.343-19.644-41.8071.0026.36O

Atom 13960N LYS B377-34.428-18.824-41.6321.0026.16N

Atoms 13961 CA LYS B377-35.012-19.811-42.5521.0026.27C

Atom 13963 CB LYS B377-34.575-19.538-44.0101.0026.51C

Atom 13966 CG LYS B377-35.470-18.561-44.8021.0028.01C

Atom 13969 CD LYS B377-34.629-17.592-45.6671.0029.99C

Atom 13972 CE LYS B377-35.493-16.605-46.4651.0031.02C

Atoms 13975 NZ LYS B377-36.420-15.819-45.5891.0032.17N

Atom 13979C LYS B377-34.647-21.243-42.1501.0025.93C

Atom 13980O LYS B377-34.380-22.084-43.0031.0025.82O

Atom 13982N SER B378-34.637-21.522-40.8521.0025.65N

Atom 13983 CA SER B378-34.324-22.860-40.3851.0025.54C

Atom 13985 CB SER B378-34.132-22.877-38.8821.0025.41C

Atom 13988 OG SER B378-32.905-22.269-38.5701.0025.67O

Atom 13990C SER B378-35.412-23.838-40.7901.0025.62C

Atom 13991O SER B378-36.495-23.435-41.1991.0025.70O

Atom 13993N THR B379-35.108-25.129-40.6901.0025.66N

Atom 13994 CA THR B379-36.038-26.175-41.0971.0025.55C

Atom 13996 CB THR B379-35.788-26.635-42.5461.0025.59C

Atom 13998 OG1 THR B379-34.391-26.899-42.7361.0025.46O

Atom 14000 CG2 THR B379-36.255-25.574-43.5281.0025.88C

Atom 14004C THR B379-35.886-27.348-40.1601.0025.45C

Atom 14005O THR B379-35.372-28.393-40.5481.0025.70O

Atom 14007N PRO B380-36.335-27.179-38.9151.0025.37N

Atom 14008 CA PRO B380-36.144-28.182-37.8761.0025.22C

Atom 14010 CB PRO B380-36.500-27.437-36.5831.0025.19C

Atom 14013 CG PRO B380-36.643-26.021-36.9551.0025.83C

Atom 14016 CD PRO B380-37.025-25.998-38.3901.0025.71C

Atom 14019C PRO B380-37.052-29.379-38.0091.0024.82C

Atom 14020O PRO B380-38.143-29.280-38.5751.0024.84O

Atom 14021N THR B381-36.607-30.493-37.4361.0024.42N

Atom 14022 CA THR B381-37.386-31.712-37.4291.0023.99C

Atom 14024 CB THR B381-36.614-32.873-36.7891.0023.99C

Atom 14026 OG1 THR B381-36.339-32.575-35.4181.0024.02O

Atom 14028 CG2 THR B381-35.302-33.117-37.5241.0023.76C

Atom 14032C THR B381-38.649-31.461-36.6361.0023.78C

Atom 14033O THR B381-38.700-30.548-35.8131.0023.89O

Atom 14035N PHE B382-39.672-32.267-36.8891.0023.53N

Atom 14036 CA PHE B382-40.905-32.204-36.1051.0022.97C

Atom 14038 CB PHE B382-41.870-33.305-36.5271.0022.89C

Atom 14041 CG PHE B382-43.079-33.394-35.6551.0022.26C

Atom 14042 CD1 PHE B382-44.189-32.601-35.9101.0021.65C

Atom 14044 CE1 PHE B382-45.300-32.672-35.0991.0020.87C

Atom 14046 CZ PHE B382-45.310-33.534-34.0161.0020.36C

Atom 14048 CE2 PHE B382-44.204-34.317-33.7441.0020.52C

Atom 14050 CD2 PHE B382-43.098-34.243-34.5561.0021.17C

Atom 14052C PHE B382-40.677-32.329-34.6051.0022.69C

Atom 14053O PHE B382-41.341-31.657-33.8341.0022.44O

Atom 14055N ASP B383-39.764-33.205-34.1911.0022.52N

Atom 14056 CA ASP B383-39.491-33.375-32.7651.0022.50C

Atom 14058 CB ASP B383-38.531-34.525-32.5271.0022.43C

Atom 14061 CG ASP B383-39.174-35.863-32.7111.0022.71C

Atom 14062 OD1 ASP B383-40.359-35.945-33.0741.0022.89O

Atom 14063 OD2 ASP B383-38.470-36.856-32.4921.0025.17O

Atom 14064C ASP B383-38.954-32.116-32.0911.0022.43C

Atom 14065O ASP B383-39.438-31.758-31.0141.0022.40O

Atom 14067N ASP B384-37.966-31.464-32.7131.0022.37N

Atom 14068 CA ASP B384-37.422-30.191-32.2131.0022.61C

Atom 14070 CB ASP B384-36.317-29.648-33.1241.0022.82C

Atom 14073 CG ASP B384-34.963-30.208-32.8071.0023.40C

Atom 14074 OD1 ASP B384-34.847-30.973-31.8321.0025.33O

Atom 14075 OD2 ASP B384-34.009-29.891-33.5451.0024.26O

Atom 14076C ASP B384-38.482-29.113-32.1301.0022.56C

Atom 14077O ASP B384-38.598-28.429-31.1081.0022.48O

Atom 14079N TYR B385-39.227-28.963-33.2271.0022.36N

Atom 14080 CA TYR B385-40.170-27.870-33.4021.0022.18C

Atom 14082 CB TYR B385-40.738-27.867-34.8121.0022.05C

Atom 14085 CG TYR B385-41.818-26.834-35.0191.0022.60C

Atom 14086 CD1 TYR B385-41.493-25.553-35.4371.0023.64C

Atom 14088 CE1 TYR B385-42.462-24.580-35.6301.0025.00C

Atom 14090 CZ TYR B385-43.788-24.882-35.4101.0026.86C

Atom 14091 OH TYR B385-44.734-23.883-35.6221.0028.48O

Atom 14093 CE2 TYR B385-44.149-26.171-34.9801.0025.95C

Atom 14095 CD2 TYR B385-43.158-27.133-34.7901.0023.94C

Atom 14097C TYR B385-41.319-27.986-32.4461.0022.13C

Atom 14098O TYR B385-41.703-27.017-31.8081.0022.95O

Atom 14100N PHE B386-41.899-29.169-32.3801.0021.80N

Atom 14101 CA PHE B386-43.048-29.394-31.5251.0021.62C

Atom 14103 CB PHE B386-43.624-30.795-31.7681.0021.73C

Atom 14106 CG PHE B386-44.834-31.104-30.9521.0021.27C

Atom 14107 CD1 PHE B386-46.034-30.447-31.1961.0022.55C

Atom 14109 CE1 PHE B386-47.164-30.732-30.4481.0023.14C

Atom 14111 CZ PHE B386-47.095-31.699-29.4461.0023.20C

Atom 14113 CE2 PHE B386-45.896-32.358-29.2081.0021.57C

Atom 14115 CD2 PHE B386-44.781-32.057-29.9591.0020.29C

Atom 14117C PHE B386-42.630-29.226-30.0731.0021.34C

Atom 14118O PHE B386-43.353-28.639-29.2841.0021.44O

Atoms 14120N GLY B387-41.447-29.725-29.7361.0020.84N

Atom 14121 CA GLY B387-40.935-29.618-28.3871.0020.57C

Atom 14124C GLY B387-40.854-28.186-27.9161.0020.26C

Atom 14125O GLY B387-40.930-27.908-26.7241.0020.86O

Atom 14127N ASN B388-40.691-27.268-28.8521.0019.81N

Atom 14128 CA ASN B388-40.758-25.853-28.5361.0019.51C

Atom 14130 CB ASN B388-39.877-25.086-29.5081.0019.42C

Atom 14133 CG ASN B388-39.593-23.700-29.0451.0019.26C

Atom 14134 OD1 ASN B388-38.916-23.513-28.0381.0018.93O

Atom 14135 ND2 ASN B388-40.105-22.709-29.7741.0017.99N

Atom 14138C ASN B388-42.200-25.320-28.6041.0019.41C

Atom 14139O ASN B388-42.591-24.447-27.8331.0019.58O

Atom 14141N ALA B389-42.989-25.848-29.5321.0019.11N

Atom 14142 CA ALA B389-44.313-25.307-29.8081.0018.87C

Atom 14144 CB ALA B389-44.897-25.949-31.0601.0018.87C

Atom 14148C ALA B389-45.264-25.460-28.6341.0018.51C

Atom 14149O ALA B389-45.916-24.511-28.2621.0018.33O

Atom 14151N TRP B390-45.344-26.652-28.0541.0018.73N

Atom 14152 CA TRP B390-46.258-26.887-26.9351.0018.74C

Atom 14154 CB TRP B390-46.389-28.377-26.5691.0018.75C

Atom 14157 CG TRP B390-45.166-29.122-26.0191.0018.46C

Atom 14158 CD1 TRP B390-44.390-30.001-26.7051.0018.75C

Atom 14160 NE1 TRP B390-43.417-30.519-25.8971.0017.56N

Atom 14162 CE2 TRP B390-43.559-30.005-24.6421.0016.67C

Atom 14163 CD2 TRP B390-44.661-29.124-24.6741.0017.50C

Atom 14164 CE3 TRP B390-45.008-28.448-23.5051.0018.38C

Atom 14166 CZ3 TRP B390-44.251-28.685-22.3471.0018.34C

Atom 14168 CH2 TRP B390-43.164-29.573-22.3611.0016.75C

Atom 14170 CZ2 TRP B390-42.805-30.234-23.4951.0015.75C

Atom 14172C TRP B390-45.861-26.066-25.7271.0018.91C

Atom 14173O TRP B390-46.707-25.691-24.9191.0019.02O

Atoms 14175N LYS B391-44.570-25.787-25.6121.0018.95N

Atom 14176 CA LYS B391-44.085-24.810-24.6431.0018.85C

Atom 14178 CB LYS B391-42.544-24.888-24.5081.0019.52C

Atom 14181 CG LYS B391-42.023-25.373-23.1431.0021.17C

Atom 14184 CD LYS B391-40.516-25.689-23.1911.0022.87C

Atom 14187 CE LYS B391-40.251-27.159-23.5081.0023.91C

Atoms 14190 NZ LYS B391-38.938-27.354-24.1911.0025.44N

Atoms 14194C LYS B391-44.537-23.400-25.0321.0017.57C

Atom 14195O LYS B391-44.937-22.629-24.1801.0017.66O

Atom 14197N SER B392-44.490-23.068-26.3141.0016.65N

Atom 14198 CA SER B392-44.879-21.718-26.7641.0016.27C

Atom 14200 CB SER B392-44.241-21.375-28.1191.0016.22C

Atom 14203 OG SER B392-44.937-21.969-29.2071.0015.94O

Atom 14205C SER B392-46.384-21.504-26.8661.0015.87C

Atom 14206O SER B392-46.825-20.395-27.0931.0015.56O

Atom 14208N SER B393-47.167-22.568-26.7241.0015.92N

Atom 14209 CA SER B393-48.629-22.474-26.7181.0015.80C

Atom 14211 CB SER B393-49.240-23.867-26.6301.0015.78C

Atom 14214 OG SER B393-49.025-24.426-25.3481.0015.00O

Atom 14216C SER B393-49.097-21.646-25.5331.0015.94C

Atom 14217O SER B393-50.115-20.948-25.5991.0015.60O

Atom 14219N SER B394-48.296-21.740-24.4711.0016.14N

Atom 14220 CA SER B394-48.487-21.091-23.1771.0016.31C

Atom 14222 CB SER B394-49.062-19.662-23.2711.0016.18C

Atom 14225 OG SER B394-50.472-19.649-23.3581.0016.57O

Atom 14227C SER B394-49.316-22.006-22.2971.0016.34C

Atom 14228O SER B394-49.822-21.595-21.2611.0016.47O

Atom 14230N GLY B395-49.403-23.268-22.7021.0016.55N

Atom 14231 CA GLY B395-50.103-24.282-21.9271.0016.79C

Atom 14234C GLY B395-49.543-24.391-20.5341.0016.80C

Atom 14235O GLY B395-50.222-24.083-19.5561.0016.74O

Atom 14237N PRO B396-48.291-24.824-20.4301.0017.07N

Atom 14238 CA PRO B396-47.698-24.930-19.1031.0017.18C

Atom 14240 CB PRO B396-46.273-25.399-19.3861.0017.09C

Atom 14243 CG PRO B396-46.087-25.237-20.8741.0017.77C

Atom 14246 CD PRO B396-47.424-25.390-21.4701.0017.20C

Atom 14249C PRO B396-47.707-23.615-18.3131.0017.17C

Atom 14250O PRO B396-47.921-23.644-17.0891.0017.10O

Atoms 14251N LEU B397-47.499-22.475-18.9831.0017.04N

Atom 14252 CA LEU B397-47.513-21.183-18.2611.0016.77C

Atom 14254 CB LEU B397-47.116-19.969-19.1351.0016.84C

Atom 14257 CG LEU B397-47.145-18.576-18.4581.0016.91C

Atom 14259 CD1 LEU B397-46.577-18.641-17.0961.0018.36C

Atom 14263 CD2 LEU B397-46.373-17.515-19.1961.0016.88C

Atoms 14267C LEU B397-48.894-20.988-17.6821.0016.24C

Atom 14268O LEU B397-49.051-20.710-16.4941.0016.09O

Atom 14270N GLN B398-49.902-21.173-18.5151.0015.72N

Atom 14271 CA GLN B398-51.262-21.093-18.0241.0015.49C

Atoms 14273 CB GLN B398-52.267-21.387-19.1201.0015.51C

Atom 14276 CG GLN B398-52.371-20.275-20.1181.0016.12C

Atoms 14279 CD GLN B398-53.436-20.545-21.1141.0017.86C

Atom 14280 OE1 GLN B398-54.509-21.028-20.7571.0020.99O

Atom 14281 NE2 GLN B398-53.170-20.239-22.3741.0018.31N

Atoms 14284C GLN B398-51.471-22.040-16.8731.0015.03C

Atom 14285O GLN B398-51.974-21.638-15.8431.0015.21O

Atoms 14287N LEU B399-51.065-23.291-17.0221.0014.72N

Atom 14288 CA LEU B399-51.361-24.254-15.9781.0014.65C

Atom 14290 CB LEU B399-51.201-25.688-16.4751.0014.44C

Atom 14293 CG LEU B399-52.250-26.191-17.4781.0014.28C

Atom 14295 CD1 LEU B399-51.907-27.633-17.8461.0015.50C

Atom 14299 CD2 LEU B399-53.713-26.077-16.9861.0010.96C

Atom 14303C LEU B399-50.554-23.995-14.7041.0014.88C

Atom 14304O LEU B399-51.100-24.161-13.6181.0015.21O

Atom 14306N ILE B400-49.291-23.562-14.8101.0014.91N

Atom 14307 CA ILE B400-48.532-23.174-13.6071.0014.89C

Atom 14309 CB ILE B400-47.158-22.574-13.9071.0015.19C

Atom 14311 CG1 ILE B400-46.189-23.674-14.3531.0016.76C

Atom 14314 CD1 ILE B400-44.777-23.162-14.7161.0018.19C

Atom 14318 CG2 ILE B400-46.603-21.906-12.6651.0013.65C

Atom 14322C ILE B400-49.288-22.137-12.8191.0014.77C

Atom 14323O ILE B400-49.485-22.302-11.6321.0015.36O

Atom 14325N PHE B401-49.717-21.071-13.4861.0014.59N

Atom 14326 CA PHE B401-50.491-20.001-12.8441.0014.22C

Atom 14328 CB PHE B401-50.825-18.900-13.8451.0014.12C

Atom 14331 CG PHE B401-49.803-17.790-13.8721.0013.83C

Atom 14332 CD1 PHE B401-50.012-16.623-13.1731.0012.77C

Atom 14334 CE1 PHE B401-49.074-15.629-13.1891.0013.09C

Atom 14336 CZ PHE B401-47.906-15.781-13.9021.0012.96C

Atom 14338 CE2 PHE B401-47.684-16.928-14.5921.0012.86C

Atom 14340 CD2 PHE B401-48.622-17.932-14.5741.0013.30C

Atom 14342C PHE B401-51.765-20.478-12.2121.0014.26C

Atom 14343O PHE B401-52.184-19.944-11.2071.0013.90O

Atom 14345N ALA B402-52.377-21.480-12.8281.0015.09N

Atom 14346 CA ALA B402-53.641-22.054-12.3641.0015.76C

Atom 14348 CB ALA B402-54.264-22.899-13.4541.0015.57C

Atom 14352C ALA B402-53.417-22.896-11.1291.0016.63C

Atom 14353O ALA B402-54.284-22.970-10.2591.0017.00O

Atom 14355N TYR B403-52.253-23.544-11.0601.0017.50N

Atom 14356 CA TYR B403-51.885-24.317-9.8941.0017.86C

Atom 14358 CB TYR B403-50.486-24.911-10.0381.0017.73C

Atom 14361 CG TYR B403-50.006-25.576-8.7641.0018.24C

Atom 14362 CD1 TYR B403-50.401-26.867-8.4361.0018.12C

Atom 14364 CE1 TYR B403-49.971-27.476-7.2731.0018.07C

Atom 14366 CZ TYR B403-49.145-26.790-6.4091.0018.62C

Atom 14367 OH TYR B403-48.727-27.383-5.2441.0017.70O

Atom 14369 CE2 TYR B403-48.748-25.499-6.7031.0018.93C

Atom 14371 CD2 TYR B403-49.177-24.901-7.8761.0018.88C

Atom 14373C TYR B403-51.966-23.461-8.6301.0018.48C

Atom 14374O TYR B403-52.494-23.908-7.6161.0018.66O

Atom 14376N PHE B404-51.468-22.232-8.6821.0018.91N

Atom 14377 CA PHE B404-51.400-21.430-7.4681.0019.53C

Atom 14379 CB PHE B404-50.395-20.325-7.6441.0019.35C

Atom 14382 CG PHE B404-49.014-20.808-7.7991.0018.79C

Atom 14383 CD1 PHE B404-48.311-21.246-6.7011.0017.67C

Atom 14385 CE1 PHE B404-47.001-21.683-6.8321.0018.44C

Atom 14387 CZ PHE B404-46.384-21.688-8.0781.0018.44C

Atom 14389 CE2 PHE B404-47.083-21.245-9.1901.0018.79C

Atom 14391 CD2 PHE B404-48.396-20.805-9.0471.0018.90C

Atom 14393C PHE B404-52.733-20.817-7.0721.0020.49C

Atom 14394O PHE B404-52.925-20.389-5.9241.0019.95O

Atom 14396N ALA B405-53.636-20.756-8.0431.0021.92N

Atom 14397 CA ALA B405-54.918-20.106-7.8721.0023.09C

Atom 14399 CB ALA B405-55.333-19.426-9.1671.0023.15C

Atom 14403C ALA B405-55.959-21.113-7.4461.0024.23C

Atom 14404O ALA B405-57.003-20.726-6.9251.0024.33O

Atom 14406N VAL B406-55.657-22.399-7.6621.0025.80N

Atom 14407 CA VAL B406-56.569-23.511-7.3551.0026.88C

Atom 14409 CB VAL B406-56.640-24.514-8.5121.0026.64C

Atom 14411 CG1 VAL B406-57.132-25.854-8.0121.0027.24C

Atom 14415 CG2 VAL B406-57.547-23.986-9.5931.0026.45C

Atom 14419C VAL B406-56.161-24.266-6.0941.0027.91C

Atom 14420O VAL B406-56.932-24.345-5.1551.0028.28O

Atom 14422N VAL B407-54.954-24.825-6.0871.0029.25N

Atom 14423 CA VAL B407-54.443-25.573-4.9411.0030.16C

Atom 14425 CB VAL B407-53.128-26.276-5.2791.0030.04C

Atom 14427 CG1 VAL B407-52.482-26.831-4.0321.0030.42C

Atom 14431 CG2 VAL B407-53.378-27.376-6.2801.0030.14C

Atom 14435C VAL B407-54.208-24.646-3.7551.0031.34C

Atom 14436O VAL B407-53.535-23.618-3.8761.0031.46O

Atoms 14438N GLN B408-54.753-25.032-2.6041.0032.63N

Atom 14439 CA GLN B408-54.727-24.191-1.4171.0033.51C

Atom 14441 CB GLN B408-55.891-24.572-5141.0033.84C

Atom 14444 CG GLN B408-56.161-23.548.5771.0035.49C

Atom 14447 CD GLN B408-57.623-23.161.6561.0037.61C

Atom 14448 OE1 GLN B408-58.519-24.006.5011.0038.23O

Atom 14449 NE2 GLN B408-57.876-21.874.8931.0038.64N

Atom 14452C GLN B408-53.399-24.274-., 6471.0033.72C

Atom 14453O GLN B408-52.852-23.253-., 2041.0033.52O

Atom 14455N ASN B409-52.889-25.491-. 4901.0033.95N

Atom 14456 CA ASN B409-51.642-25.707.2261.0034.16C

Atom 14458 CB ASN B409-51.865-26.6651.3911.0034.25C

Atom 14461 CG ASN B409-52.756-26.0692.4591.0034.39C

Atom 14462 OD1 ASN B409-52.269-25.5773.4801.0034.40O

Atom 14463 ND2 ASN B409-54.070-26.0892.2221.0034.12N

Atom 14466C ASN B409-50.582-26.244-. 7091.0034.12C

Atom 14467O ASN B409-50.578-27.422-1.0461.0034.41O

Atom 14469N ILE B410-49.681-25.369-1.1271.0034.07N

Atom 14470 CA ILE B410-48.699-25.718-2.1381.0034.08C

Atom 14472 CB ILE B410-48.138-24.455-2.8401.0034.15C

Atom 14474 CG1 ILE B410-47.274-23.610-1.8911.0034.26C

Atom 14477 CD1 ILE B410-47.216-22.139-2.2491.0034.10C

Atom 14481 CG2 ILE B410-49.290-23.634-3.4041.0034.49C

Atom 14485C ILE B410-47.586-26.553-1.5331.0033.93C

Atom 14486O ILE B410-47.181-26.317-. 4051.0033.80O

Atom 14488N LYS B411-47.123-27.546-2.2851.0034.12N

Atom 14489 CA LYS B411-46.012-28.395-1.8741.0034.45C

Atom 14491 CB LYS B411-46.414-29.873-1.9071.0034.67C

Atom 14494 CG LYS B411-47.850-30.130-1.4601.0035.79C

Atom 14497 CD LYS B411-48.102-31.586-1.0521.0037.60C

Atom 14500 CE LYS B411-49.450-31.728-. 3091.0038.80C

Atom 14503 NZ LYS B411-49.568-32.992.4881.0039.20N

Atoms 14507C LYS B411-44.843-28.132-2.8101.0034.33C

Atom 14508O LYS B411-45.038-27.956-4.0061.0034.14O

Atom 14510N LYS B412-43.631-28.102-2.2651.0034.50N

Atom 14511 CA LYS B412-42.460-27.688-3.0421.0034.69C

Atom 14513 CB LYS B412-41.242-27.398-2.1541.0035.13C

Atom 14516 CG LYS B412-41.205-25.960-1.6131.0036.90C

Atom 14519 CD LYS B412-40.079-25.749-., 5881.0038.57C

Atom 14522 CE LYS B412-40.546-24.852.5551.0039.55C

Atom 14525 NZ LYS B412-39.491-24.6441.5871.0040.83N

Atom 14529C LYS B412-42.075-28.687-4.1031.0034.13C

Atom 14530O LYS B412-41.468-28.308-5.0931.0034.21O

Atoms 14532N GLU B413-42.408-29.958-3.9101.0033.54N

Atom 14533 CA GLU B413-42.095-30.949-4.9331.0033.19C

Atoms 14535 CB GLU B413-41.886-32.335-4.3301.0033.44C

Atom 14538 CG GLU B413-43.127-33.037-3.8071.0034.37C

Atoms 14541 CD GLU B413-42.834-34.490-3.4991.0035.56C

Atom 14542 OE1 GLU B413-42.662-35.264-4.4711.0035.30O

Atom 14543 OE2 GLU B413-42.751-34.847-2.2971.0036.69O

Atoms 14544C GLU B413-43.157-30.965-6.0291.0032.47C

Atom 14545O GLU B413-42.846-31.232-7.1931.0032.28O

Atoms 14547N GLU B414-44.403-30.676-5.6521.0031.58N

Atom 14548 CA GLU B414-45.482-30.512-6.6141.0030.99C

Atom 14550 CB GLU B414-46.781-30.101-5.9271.0030.98C

Atom 14553 CG GLU B414-47.732-31.245-5.6421.0031.82C

Atom 14556 CD GLU B414-49.100-30.774-5.1381.0034.29C

Atom 14557 OE1 GLU B414-49.258-29.581-4.7771.0035.53O

Atom 14558 OE2 GLU B414-50.036-31.603-5.1011.0036.44O

Atoms 14559C GLU B414-45.104-29.455-7.6281.0030.59C

Atom 14560O GLU B414-45.169-29.687-8.8281.0030.37O

Atom 14562N ILE B415-44.684-28.295-7.1401.0030.49N

Atom 14563 CA ILE B415-44.367-27.177-8.0281.0030.40C

Atom 14565 CB ILE B415-44.412-25.797-7.3201.0030.40C

Atom 14567 CG1 ILE B415-43.235-25.589-6.3881.0030.36C

Atom 14570 CD1 ILE B415-43.373-24.313-5.6111.0031.01C

Atom 14574 CG2 ILE B415-45.686-25.644-6.5231.0030.85C

Atom 14578C ILE B415-43.037-27.347-8.7301.0030.12C

Atom 14579O ILE B415-42.870-26.865-9.8401.0030.42O

Atoms 14581N GLU B416-42.095-28.030-8.0991.0029.75N

Atom 14582 CA GLU B416-40.799-28.249-8.7191.0029.70C

Atoms 14584 CB GLU B416-39.825-28.777-7.6901.0030.02C

Atom 14587 CG GLU B416-38.386-28.426-7.9481.0031.20C

Atom 14590 CD GLU B416-37.523-28.839-6.7761.0032.91C

Atom 14591 OE1 GLU B416-38.008-28.723-5.6321.0032.37O

Atom 14592 OE2 GLU B416-36.377-29.294-6.9941.0035.31O

Atom 14593C GLU B416-40.917-29.222-9.8901.0029.24C

Atom 14594O GLU B416-40.121-29.177-10.8351.0028.86O

Atom 14596N ASN B417-41.915-30.097-9.8191.0028.81N

Atom 14597 CA ASN B417-42.252-30.960-10.9411.0028.66C

Atom 14599 CB ASN B417-43.165-32.105-10.5031.0028.72C

Atom 14602 CG ASN B417-42.379-33.285-9.9731.0029.78C

Atom 14603 OD1 ASN B417-41.887-34.108-10.7441.0030.39O

Atom 14604 ND2 ASN B417-42.223-33.358-8.6531.0031.45N

Atom 14607C ASN B417-42.888-30.183-12.0671.0028.32C

Atom 14608O ASN B417-42.611-30.456-13.2321.0027.95O

Atom 14610N LEU B418-43.740-29.217-11.7131.0028.23N

Atom 14611 CA LEU B418-44.349-28.313-12.6971.0027.92C

Atom 14613 CB LEU B418-45.298-27.320-12.0231.0027.48C

Atom 14616 CG LEU B418-46.636-27.896-11.5531.0027.02C

Atom 14618 CD1 LEU B418-47.393-26.882-10.6911.0026.70C

Atom 14622 CD2 LEU B418-47.499-28.355-12.7201.0025.90C

Atoms 14626C LEU B418-43.275-27.567-13.4911.0028.20C

Atom 14627O LEU B418-43.310-27.541-14.7331.0027.90O

Atom 14629N GLN B419-42.308-26.995-12.7701.0028.43N

Atom 14630 CA GLN B419-41.170-26.315-13.3951.0028.72C

Atom 14632 CB GLN B419-40.223-25.746-12.3471.0028.81C

Atom 14635 CG GLN B419-40.592-24.332-11.9461.0030.14C

Atom 14638 CD GLN B419-39.535-23.671-11.0921.0032.05C

Atom 14639 OE1 GLN B419-39.246-22.477-11.2571.0033.88O

Atom 14640 NE2 GLN B419-38.948-24.437-10.1701.0031.84N

Atom 14643C GLN B419-40.390-27.179-14.3701.0028.83C

Atom 14644O GLN B419-39.922-26.668-15.3861.0028.72O

Atoms 14646N LYS B420-40.265-28.475-14.0671.0029.21N

Atom 14647 CA LYS B420-39.613-29.451-14.9681.0029.26C

Atom 14649 CB LYS B420-38.924-30.555-14.1431.0029.42C

Atom 14652 CG LYS B420-37.800-30.052-13.2071.0030.58C

Atom 14655 CD LYS B420-37.373-31.113-12.1511.0032.35C

Atom 14658 CE LYS B420-36.572-30.506-10.9551.0033.05C

Atoms 14661 NZ LYS B420-36.520-31.368-9.7021.0032.62N

Atom 14665C LYS B420-40.579-30.057-16.0211.0028.96C

Atom 14666O LYS B420-40.216-30.965-16.7531.0028.66O

Atom 14668N TYR B421-41.804-29.543-16.0881.0029.01N

Atom 14669 CA TYR B421-42.777-29.893-17.1341.0029.16C

Atom 14671 CB TYR B421-42.209-29.602-18.5341.0029.48C

Atom 14674 CG TYR B421-41.968-28.127-18.7731.0031.04C

Atom 14675 CD1 TYR B421-43.018-27.219-18.7161.0032.54C

Atom 14677 CE1 TYR B421-42.815-25.878-18.9141.0033.35C

Atom 14679 CZ TYR B421-41.556-25.413-19.1931.0034.56C

Atom 14680 OH TYR B421-41.377-24.066-19.3841.0037.99O

Atom 14682 CE2 TYR B421-40.490-26.278-19.2671.0033.56C

Atom 14684 CD2 TYR B421-40.702-27.638-19.0511.0032.75C

Atom 14686C TYR B421-43.345-31.311-17.0421.0028.60C

Atom 14687O TYR B421-43.395-32.046-18.0251.0028.49O

Atom 14689N HIS B422-43.808-31.662-15.8461.0028.18N

Atom 14690 CA HIS B422-44.507-32.919-15.5941.0027.66C

Atom 14692 CB HIS B422-45.082-32.914-14.1801.0027.73C

Atom 14695 CG HIS B422-45.500-34.264-13.6851.0028.14C

Atom 14696 ND1 HIS B422-44.597-35.195-13.2171.0029.15N

Atom 14698 CE1 HIS B422-45.247-36.277-12.8291.0029.50C

Atom 14700 NE2 HIS B422-46.539-36.078-13.0221.0028.69N

Atom 14702 CD2 HIS B422-46.724-34.827-13.5521.0027.24C

Atom 14704C HIS B422-45.650-33.164-16.5751.0027.29C

Atom 14705O HIS B422-46.463-32.269-16.8531.0026.86O

Atom 14707N ASP B423-45.712-34.402-17.0601.0026.96N

Atom 14708 CA ASP B423-46.772-34.883-17.9521.0026.78C

Atom 14710 CB ASP B423-46.792-36.413-17.9391.0027.01C

Atom 14713 CG ASP B423-45.594-37.018-18.6461.0028.21C

Atom 14714 OD1 ASP B423-45.100-36.378-19.6021.0031.33O

Atom 14715 OD2 ASP B423-45.153-38.130-18.2621.0028.39O

Atom 14716C ASP B423-48.187-34.383-17.6511.0026.21C

Atom 14717O ASP B423-49.015-34.336-18.5561.0026.75O

Atom 14719N ILE B424-48.463-34.042-16.3911.0025.11N

Atom 14720 CA ILE B424-49.773-33.553-15.9561.0023.82C

Atom 14722 CB ILE B424-49.798-33.310-14.4391.0023.67C

Atom 14724 CG1 ILE B424-51.196-32.990-13.9381.0022.97C

Atom 14727 CD1 ILE B424-51.220-32.693-12.4651.0022.06C

Atom 14731 CG2 ILE B424-48.859-32.171-14.0651.0024.35C

Atom 14735C ILE B424-50.102-32.265-16.6691.0023.08C

Atom 14736O ILE B424-51.265-32.025-17.0231.0022.99O

Atom 14738N ILE B425-49.082-31.436-16.8861.0022.22N

Atom 14739 CA ILE B425-49.282-30.199-17.6331.0021.61C

Atom 14741 CB ILE B425-48.796-28.959-16.8481.0021.18C

Atom 14743 CG1 ILE B425-47.279-28.853-16.8041.0019.47C

Atom 14746 CD1 ILE B425-46.850-27.581-16.1401.0018.00C

Atom 14750 CG2 ILE B425-49.357-28.977-15.4281.0020.75C

Atom 14754C ILE B425-48.665-30.255-19.0331.0021.73C

Atom 14755O ILE B425-49.100-29.523-19.9121.0021.75O

Atom 14757N SER B426-47.686-31.134-19.2581.0021.74N

Atom 14758 CA SER B426-47.016-31.174-20.5601.0021.53C

Atom 14760 CB SER B426-45.639-31.876-20.5161.0021.66C

Atom 14763 OG SER B426-45.724-33.281-20.4051.0022.19O

Atom 14765C SER B426-47.922-31.798-21.5821.0021.19C

Atom 14766O SER B426-47.950-31.358-22.7211.0021.37O

Atom 14768N ARG B427-48.692-32.800-21.1771.0020.91N

Atom 14769 CA ARG B427-49.532-33.504-22.1431.0020.78C

Atom 14771 CB ARG B427-50.038-34.840-21.6161.0020.94C

Atom 14774 CG ARG B427-49.006-35.887-21.8741.0022.76C

Atom 14777 CD ARG B427-49.158-37.101-21.0251.0026.75C

Atom 14780 NE ARG B427-47.960-37.927-21.1851.0029.36N

Atom 14782 CZ ARG B427-47.574-38.887-20.3521.0030.25C

Atom 14783 NH1 ARG B427-48.293-39.179-19.2661.0030.27N

Atom 14786 NH2 ARG B427-46.447-39.547-20.6111.0031.25N

Atom 14789C ARG B427-50.646-32.650-22.6681.0020.07C

Atom 14790O ARG B427-50.724-32.466-23.8661.0020.13O

Atom 14792N PRO B428-51.482-32.091-21.7861.0019.38N

Atom 14793 CA PRO B428-52.533-31.202-22.2641.0019.05C

Atom 14795 CB PRO B428-53.046-30.547-20.9901.0019.13C

Atom 14798 CG PRO B428-52.696-31.476-19.9181.0019.55C

Atom 14801 CD PRO B428-51.443-32.161-20.3191.0019.20C

Atom 14804C PRO B428-52.016-30.135-23.2271.0018.84C

Atom 14805O PRO B428-52.688-29.802-24.2051.0018.73O

Atom 14806N SER B429-50.828-29.608-22.9641.0018.57N

Atom 14807 CA SER B429-50.208-28.679-23.8991.0018.64C

Atom 14809 CB SER B429-48.960-28.086-23.2911.0018.46C

Atom 14812 OG SER B429-49.141-27.980-21.9111.0019.08O

Atom 14814C SER B429-49.877-29.315-25.2601.0018.52C

Atom 14815O SER B429-49.886-28.633-26.2761.0019.02O

Atoms 14817N HIS B430-49.579-30.606-25.2971.0018.29N

Atom 14818 CA HIS B430-49.457-31.273-26.5831.0018.25C

Atom 14820 CB HIS B430-49.085-32.765-26.4671.0018.40C

Atom 14823 CG HIS B430-47.753-33.024-25.8061.0019.41C

Atom 14824 ND1 HIS B430-46.776-32.055-25.6571.0019.55N

Atom 14826 CE1 HIS B430-45.729-32.576-25.0431.0017.77C

Atom 14828 NE2 HIS B430-45.981-33.849-24.8001.0018.52N

Atom 14830 CD2 HIS B430-47.232-34.160-25.2771.0019.19C

Atom 14832C HIS B430-50.789-31.105-27.3061.0017.93C

Atom 14833O HIS B430-50.816-30.599-28.4171.0018.54O

Atom 14835N ILE B431-51.897-31.479-26.6651.0017.34N

Atom 14836 CA ILE B431-53.217-31.372-27.3011.0016.58C

Atom 14838 CB ILE B431-54.400-31.738-26.3751.0016.53C

Atom 14840 CG1 ILE B431-54.225-33.123-25.7281.0016.06C

Atom 14843 CD1 ILE B431-54.069-34.212-26.6981.0016.05C

Atom 14847 CG2 ILE B431-55.701-31.666-27.1491.0015.49C

Atom 14851C ILE B431-53.431-29.949-27.7481.0016.35C

Atom 14852O ILE B431-53.856-29.712-28.8601.0016.74O

Atom 14854N PHE B432-53.110-29.003-26.8811.0016.15N

Atom 14855 CA PHE B432-53.353-27.577-27.1451.0016.19C

Atom 14857 CB PHE B432-52.811-26.776-25.9561.0016.36C

Atom 14860 CG PHE B432-53.007-25.295-26.0431.0016.54C

Atom 14861 CD1 PHE B432-53.869-24.708-26.9461.0016.55C

Atom 14863 CE1 PHE B432-54.007-23.334-26.9741.0017.89C

Atom 14865 CZ PHE B432-53.305-22.538-26.0801.0017.96C

Atom 14867 CE2 PHE B432-52.461-23.114-25.1691.0017.30C

Atom 14869 CD2 PHE B432-52.323-24.482-25.1511.0017.54C

Atom 14871C PHE B432-52.726-27.104-28.4521.0015.93C

Atom 14872O PHE B432-53.398-26.525-29.3031.0015.63O

Atom 14874N ARG B433-51.438-27.387-28.5941.0015.79N

Atom 14875 CA ARG B433-50.674-27.044-29.7781.0015.74C

Atom 14877 CB ARG B433-49.196-27.279-29.4701.0015.68C

Atom 14880 CG ARG B433-48.259-27.218-30.6651.0016.39C

Atom 14883 CD ARG B433-48.348-25.919-31.3881.0016.27C

Atom 14886 NE ARG B433-47.969-24.850-30.4921.0017.34N

Atom 14888 CZ ARG B433-48.210-23.565-30.7031.0017.89C

Atom 14889 NH1 ARG B433-48.834-23.142-31.8031.0016.79N

Atom 14892 NH2 ARG B433-47.805-22.701-29.7921.0018.53N

Atom 14895C ARG B433-51.114-27.852-31.0111.0015.85C

Atom 14896O ARG B433-51.197-27.328-32.1201.0015.40O

Atoms 14898N LEU B434-51.381-29.134-30.8131.0016.18N

Atoms 14899 CA LEU B434-51.794-29.986-31.9021.0016.58C

Atoms 14901 CB LEU B434-51.802-31.453-31.4681.0016.79C

Atom 14904 CG LEU B434-50.408-32.055-31.2321.0017.49C

Atom 14906 CD1 LEU B434-50.486-33.548-30.8641.0016.63C

Atom 14910 CD2 LEU B434-49.511-31.836-32.4671.0018.00C

Atoms 14914C LEU B434-53.158-29.559-32.4231.0017.07C

Atom 14915O LEU B434-53.333-29.442-33.6331.0017.44O

Atom 14917N CYS B435-54.118-29.308-31.5321.0017.23N

Atom 14918 CA CYS B435-55.419-28.778-31.9471.0017.44C

Atom 14920 CB CYS B435-56.301-28.529-30.7461.0017.38C

Atom 14923 SG CYS B435-56.825-29.993-29.9711.0017.90S

Atom 14925C CYS B435-55.295-27.460-32.6961.0017.78C

Atom 14926O CYS B435-55.978-27.232-33.7011.0017.44O

Atoms 14928N ASN B436-54.442-26.585-32.1781.0018.31N

Atom 14929 CA ASN B436-54.248-25.267-32.7691.0019.14C

Atom 14931 CB ASN B436-53.392-24.394-31.8441.0019.31C

Atom 14934 CG ASN B436-52.984-23.068-32.4781.0020.07C

Atom 14935 OD1 ASN B436-53.456-22.686-33.5551.0022.72O

Atom 14936 ND2 ASN B436-52.099-22.356-31.8001.0020.90N

Atom 14939C ASN B436-53.615-25.345-34.1571.0019.51C

Atom 14940O ASN B436-54.173-24.840-35.1311.0019.79O

Atom 14942N ASP B437-52.446-25.965-34.2451.0019.85N

Atom 14943 CA ASP B437-51.754-26.058-35.5171.0020.01C

Atom 14945 CB ASP B437-50.340-26.638-35.3311.0020.00C

Atom 14948 CG ASP B437-49.397-25.675-34.5571.0021.23C

Atom 14949 OD1 ASP B437-49.902-24.749-33.8771.0022.90O

Atom 14950 OD2 ASP B437-48.149-25.821-34.6321.0022.18O

Atom 14951C ASP B437-52.629-26.838-36.5121.0020.00C

Atom 14952O ASP B437-52.678-26.491-37.6951.0020.02O

Atoms 14954N LEU B438-53.372-27.836-36.0211.0020.02N

Atoms 14955 CA LEU B438-54.352-28.558-36.8581.0020.18C

Atoms 14957 CB LEU B438-55.144-29.593-36.0491.0019.88C

Atom 14960 CG LEU B438-54.699-31.050-36.1421.0018.97C

Atom 14962 CD1 LEU B438-55.537-31.869-35.2001.0018.86C

Atoms 14966 CD2 LEU B438-54.818-31.585-37.5501.0016.23C

Atoms 14970C LEU B438-55.358-27.644-37.5641.0020.60C

Atom 14971O LEU B438-55.717-27.889-38.7121.0020.30O

Atom 14973N ALA B439-55.825-26.620-36.8531.0021.39N

Atom 14974 CA ALA B439-56.802-25.654-37.3771.0021.96C

Atom 14976 CB ALA B439-57.306-24.741-36.2421.0021.77C

Atom 14980C ALA B439-56.214-24.805-38.4941.0022.47C

Atom 14981O ALA B439-56.850-24.559-39.5171.0022.13O

Atom 14983N SER B440-54.983-24.370-38.2821.0023.40N

Atom 14984 CA SER B440-54.337-23.428-39.1691.0024.40C

Atom 14986 CB SER B440-53.423-22.529-38.3421.0024.44C

Atom 14989 OG SER B440-52.994-23.206-37.1661.0025.19O

Atom 14991C SER B440-53.544-24.103-40.2891.0025.15C

Atom 14992O SER B440-53.093-23.424-41.2101.0025.24O

Atom 14994N ALA B441-53.392-25.428-40.2221.0025.99N

Atom 14995 CA ALA B441-52.488-26.160-41.1191.0026.53C

Atom 14997 CB ALA B441-52.532-27.655-40.8301.0026.26C

Atom 15001C ALA B441-52.726-25.903-42.6081.0027.31C

Atom 15002O ALA B441-51.811-25.489-43.3101.0027.26O

Atom 15004N SER B442-53.940-26.134-43.0981.0028.45N

Atom 15005 CA SER B442-54.138-26.138-44.5451.0029.47C

Atom 15007 CB SER B442-55.477-26.769-44.9361.0029.40C

Atom 15010 OG SER B442-56.454-25.784-45.1811.0030.36O

Atom 15012C SER B442-53.966-24.731-45.1251.0030.22C

Atom 15013O SER B442-53.304-24.562-46.1391.0030.26O

Atom 15015N ALA B443-54.537-23.729-44.4671.0031.38N

Atom 15016 CA ALA B443-54.308-22.333-44.8351.0032.22C

Atom 15018 CB ALA B443-55.057-21.410-43.8931.0032.28C

Atom 15022C ALA B443-52.820-21.992-44.8181.0033.12C

Atom 15023O ALA B443-52.302-21.419-45.7661.0033.24O

Atom 15025N GLU B444-52.136-22.351-43.7361.0034.43N

Atom 15026 CA GLU B444-50.711-22.033-43.5821.0035.35C

Atom 15028 CB GLU B444-50.237-22.271-42.1341.0035.46C

Atom 15031 CG GLU B444-50.757-21.227-41.1261.0036.42C

Atom 15034 CD GLU B444-50.178-21.376-39.7081.0037.82C

Atom 15035 OE1 GLU B444-49.965-22.506-39.2241.0037.92O

Atom 15036 OE2 GLU B444-49.955-20.344-39.0491.0040.09O

Atom 15037C GLU B444-49.840-22.794-44.5941.0035.87C

Atom 15038O GLU B444-48.870-22.239-45.1071.0035.85O

Atom 15040N ILE B445-50.193-24.048-44.8831.0036.63N

Atom 15041 CA ILE B445-49.517-24.837-45.9281.0037.21C

Atom 15043 CB ILE B445-49.854-26.366-45.8321.0037.15C

Atom 15045 CG1 ILE B445-49.181-26.991-44.6091.0036.85C

Atom 15048 CD1 ILE B445-49.867-28.244-44.1021.0036.62C

Atom 15052 CG2 ILE B445-49.416-27.120-47.0931.0036.66C

Atom 15056C ILE B445-49.933-24.289-47.2901.0037.88C

Atom 15057O ILE B445-50.926-24.733-47.8741.0038.20O

Atom 15059N ALA B446-49.175-23.314-47.7851.0038.56N

Atom 15060 CA ALA B446-49.544-22.575-48.9921.0039.03C

Atom 15062 CB ALA B446-49.833-23.522-50.1691.0039.19C

Atom 15066C ALA B446-50.768-21.740-48.6851.0039.42C

Atom 15067O ALA B446-51.866-22.288-48.7421.0039.26O

Atom 15069N ARG B447-50.650-20.443-48.3611.0040.06N

Atom 15070 CA ARG B447-49.426-19.589-48.3611.0040.54C

Atom 15072 CB ARG B447-49.276-18.901-46.9861.0040.70C

Atom 15075 CG ARG B447-50.121-17.634-46.8361.0041.82C

Atom 15078 CD ARG B447-50.292-17.234-45.3771.0042.99C

Atom 15081 NE ARG B447-51.628-17.546-44.8641.0044.22N

Atom 15083 CZ ARG B447-51.924-17.766-43.5801.0046.00C

Atom 15084 NH1 ARG B447-50.977-17.730-42.6331.0046.34N

Atom 15087 NH2 ARG B447-53.184-18.039-43.2361.0046.39N

Atom 15090C ARG B447-48.095-20.208-48.8371.0040.35C

Atom 15091O ARG B447-47.897-20.403-50.0381.0040.95O

Atom 15093N GLY B448-47.170-20.442-47.9181.0039.87N

Atom 15094 CA GLY B448-46.020-21.306-48.1621.0039.52C

Atom 15097C GLY B448-45.258-21.517-46.8651.0039.26C

Atom 15098O GLY B448-44.071-21.842-46.8851.0039.15O

Atom 15100N GLU B449-45.966-21.344-45.7421.0038.85N

Atom 15101 CA GLU B449-45.365-21.215-44.4261.0038.45C

Atom 15103 CB GLU B449-46.288-20.472-43.4441.0038.76C

Atom 15106 CG GLU B449-46.346-18.943-43.6361.0040.34C

Atom 15109 CD GLU B449-47.486-18.257-42.8391.0042.09C

Atom 15110 OE1 GLU B449-47.897-18.787-41.7801.0043.23O

Atom 15111 OE2 GLU B449-47.972-17.184-43.2741.0042.13O

Atom 15112C GLU B449-45.073-22.600-43.9061.0037.54C

Atom 15113O GLU B449-45.810-23.553-44.1671.0037.34O

Atom 15115N THR B450-43.986-22.688-43.1591.0036.47N

Atom 15116 CA THR B450-43.459-23.950-42.7021.0035.65C

Atom 15118 CB THR B450-42.017-24.105-43.2451.0035.81C

Atom 15120 OG1 THR B450-41.593-25.465-43.1091.0037.67O

Atom 15122 CG2 THR B450-41.029-23.152-42.5381.0036.21C

Atom 15126C THR B450-43.528-24.084-41.1661.0034.22C

Atom 15127O THR B450-43.165-25.127-40.6191.0034.00O

Atom 15129N ALA B451-44.024-23.034-40.4951.0032.69N

Atom 15130 CA ALA B451-44.144-22.974-39.0261.0031.28C

Atom 15132 CB ALA B451-43.952-21.546-38.5451.0031.06C

Atom 15136C ALA B451-45.495-23.500-38.5471.0029.97C

Atom 15137O ALA B451-46.337-22.735-38.0821.0030.08O

Atom 15139N ASN B452-45.690-24.809-38.6561.0028.19N

Atom 15140 CA ASN B452-46.935-25.444-38.2721.0026.73C

Atom 15142 CB ASN B452-47.929-25.339-39.4221.0026.45C

Atom 15145 CG ASN B452-49.311-25.832-39.0571.0025.38C

Atom 15146 OD1 ASN B452-49.608-27.004-39.1951.0024.57O

Atom 15147 ND2 ASN B452-50.171-24.928-38.6181.0024.44N

Atom 15150C ASN B452-46.631-26.889-37.9521.0026.05C

Atom 15151O ASN B452-45.930-27.544-38.6951.0026.21O

Atom 15153N SER B453-47.131-27.388-36.8341.0025.30N

Atom 15154 CA SER B453-46.843-28.760-36.4321.0024.72C

Atom 15156 CB SER B453-47.638-29.139-35.1741.0024.81C

Atom 15159 OG SER B453-47.143-28.455-34.0311.0024.36O

Atom 15161C SER B453-47.111-29.770-37.5431.0024.12C

Atom 15162O SER B453-46.325-30.679-37.7431.0024.33O

Atom 15164N VAL B454-48.202-29.606-38.2721.0023.57N

Atom 15165 CA VAL B454-48.546-30.541-39.3281.0023.27C

Atom 15167 CB VAL B454-50.001-30.361-39.7951.0023.06C

Atom 15169 CG1 VAL B454-50.363-31.385-40.8291.0022.41C

Atom 15173 CG2 VAL B454-50.946-30.489-38.6221.0022.80C

Atom 15177C VAL B454-47.581-30.473-40.5211.0023.83C

Atom 15178O VAL B454-47.370-31.493-41.1751.0024.48O

Atom 15180N SER B455-46.981-29.309-40.8031.0023.99N

Atom 15181 CA SER B455-45.978-29.198-41.8811.0024.22C

Atom 15183 CB SER B455-45.577-27.767-42.1111.0024.02C

Atom 15186 OG SER B455-46.655-27.098-42.6891.0025.57O

Atom 15188C SER B455-44.708-29.949-41.5821.0024.65C

Atom 15189O SER B455-44.211-30.700-42.4171.0025.23O

Atom 15191N CYS B456-44.151-29.700-40.4051.0024.82N

Atom 15192 CA CYS B456-43.024-30.462-39.9351.0024.81C

Atom 15194 CB CYS B456-42.765-30.170-38.4701.0024.92C

Atom 15197 SG CYS B456-42.139-28.541-38.1901.0025.18S

Atom 15199C CYS B456-43.304-31.938-40.1241.0024.84C

Atom 15200O CYS B456-42.507-32.634-40.7281.0025.34O

Atom 15202N TYR B457-44.442-32.421-39.6441.0024.75N

Atom 15203 CA TYR B457-44.735-33.838-39.7781.0024.85C

Atom 15205 CB TYR B457-46.069-34.197-39.1421.0024.64C

Atom 15208 CG TYR B457-46.057-35.537-38.4511.0024.00C

Atom 15209 CD1 TYR B457-45.846-35.635-37.0831.0024.19C

Atom 15211 CE1 TYR B457-45.848-36.873-36.4361.0023.72C

Atom 15213 CZ TYR B457-46.059-38.025-37.1701.0023.27C

Atom 15214 OH TYR B457-46.063-39.244-36.5541.0022.94O

Atom 15216 CE2 TYR B457-46.268-37.961-38.5281.0023.68C

Atom 15218 CD2 TYR B457-46.265-36.711-39.1631.0024.16C

Atom 15220C TYR B457-44.676-34.267-41.2511.0025.30C

Atom 15221O TYR B457-43.965-35.208-41.5841.0024.94O

Atom 15223N MET B458-45.388-33.569-42.1341.0026.02N

Atom 15224 CA MET B458-45.207-33.775-43.5851.0026.76C

Atom 15226 CB MET B458-45.913-32.685-44.4071.0026.84C

Atom 15229 CG MET B458-47.419-32.720-44.4291.0027.32C

Atom 15232 SD MET B458-48.092-31.238-45.2291.0027.76S

Atom 15233 CE MET B458-47.283-31.311-46.8301.0026.95C

Atom 15237C MET B458-43.723-33.759-43.9961.0027.06C

Atom 15238O MET B458-43.192-34.746-44.4851.0026.94O

Atom 15240N ARG B459-43.069-32.624-43.8001.0027.58N

Atom 15241 CA ARG B459-41.720-32.419-44.2891.0028.38C

Atom 15243 CB ARG B459-41.313-30.965-44.0411.0028.96C

Atom 15246 CG ARG B459-39.862-30.642-44.3281.0031.93C

Atom 15249 CD ARG B459-39.656-29.139-44.4801.0036.88C

Atom 15252 NE ARG B459-40.318-28.349-43.4271.0041.70N

Atom 15254 CZ ARG B459-39.890-28.241-42.1611.0045.68C

Atom 15255 NH1 ARG B459-38.795-28.899-41.7511.0048.08N

Atom 15258 NH2 ARG B459-40.566-27.489-41.2841.0045.92N

Atom 15261C ARG B459-40.717-33.401-43.6721.0028.03C

Atom 15262O ARG B459-39.829-33.881-44.3561.0028.13O

Atom 15264N THR B460-40.882-33.711-42.3931.0027.88N

Atom 15265 CA THR B460-40.002-34.635-41.6641.0027.75C

Atom 15267 CB THR B460-40.240-34.502-40.1341.0027.79C

Atom 15269 OG1 THR B460-39.805-33.209-39.6891.0027.98O

Atom 15271 CG2 THR B460-39.519-35.589-39.3561.0027.46C

Atom 15275C THR B460-40.171-36.114-42.0451.0027.72C

Atom 15276O THR B460-39.211-36.857-42.0691.0027.60O

Atom 15278N LYS B461-41.398-36.538-42.3131.0028.05N

Atom 15279 CA LYS B461-41.701-37.929-42.6491.0028.25C

Atom 15281 CB LYS B461-42.972-38.381-41.9141.0028.32C

Atom 15284 CG LYS B461-42.767-38.763-40.4531.0028.57C

Atom 15287 CD LYS B461-42.569-40.271-40.2991.0029.79C

Atom 15290 CE LYS B461-41.913-40.651-38.9701.0030.32C

Atom 15293 NZ LYS B461-42.651-40.184-37.7491.0030.60N

Atom 15297C LYS B461-41.876-38.139-44.1551.0028.50C

Atom 15298O LYS B461-42.071-39.269-44.5981.0028.58O

Atom 15300N GLY B462-41.818-37.057-44.9331.0028.79N

Atom 15301 CA GLY B462-41.978-37.114-46.3851.0029.04C

Atom 15304C GLY B462-43.333-37.610-46.8531.0029.39C

Atom 15305O GLY B462-43.410-38.452-47.7381.0029.53O

Atom 15307N ILE B463-44.406-37.081-46.2701.0029.91N

Atom 15308 CA ILE B463-45.764-37.552-46.5721.0030.27C

Atom 15310 CB ILE B463-46.333-38.444-45.4331.0030.13C

Atom 15312 CG1 ILE B463-46.308-37.706-44.0921.0030.22C

Atom 15315 CD1 ILE B463-46.983-38.462-42.9651.0030.14C

Atom 15319 CG2 ILE B463-45.558-39.740-45.3401.0029.85C

Atom 15323C ILE B463-46.775-36.429-46.8811.0030.75C

Atom 15324O ILE B463-46.595-35.270-46.4951.0030.52O

Atom 15326N SER B464-47.842-36.822-47.5811.0031.33N

Atom 15327 CA SER B464-48.951-35.944-47.9521.0031.68C

Atom 15329 CB SER B464-49.948-36.709-48.8301.0032.02C

Atom 15332 OG SER B464-50.547-37.793-48.1231.0032.84O

Atom 15334C SER B464-49.705-35.396-46.7471.0031.62C

Atom 15335O SER B464-49.897-36.097-45.7471.0031.69O

Atom 15337N GLU B465-50.165-34.153-46.8741.0031.42N

Atom 15338 CA GLU B465-50.881-33.466-45.8031.0031.20C

Atom 15340 CB GLU B465-51.465-32.141-46.3241.0031.33C

Atom 15343 CG GLU B465-52.441-31.455-45.3591.0031.42C

Atom 15346 CD GLU B465-52.768-30.006-45.7121.0031.30C

Atom 15347 OE1 GLU B465-52.325-29.490-46.7651.0030.56O

Atom 15348 OE2 GLU B465-53.487-29.380-44.9061.0031.84O

Atom 15349C GLU B465-51.985-34.325-45.2021.0030.97C

Atom 15350O GLU B465-52.175-34.327-43.9921.0030.72O

Atom 15352N GLU B466-52.709-35.052-46.0551.0030.98N

Atom 15353 CA GLU B466-53.865-35.833-45.6181.0030.65C

Atom 15355 CB GLU B466-54.553-36.541-46.7881.0030.62C

Atom 15358 CG GLU B466-55.733-37.401-46.3361.0031.50C

Atom 15361 CD GLU B466-56.353-38.240-47.4461.0033.14C

Atom 15362 OE1 GLU B466-56.512-37.736-48.5811.0034.40O

Atom 15363 OE2 GLU B466-56.699-39.413-47.1731.0033.21O

Atom 15364C GLU B466-53.477-36.851-44.5641.0030.17C

Atom 15365O GLU B466-54.215-37.049-43.6061.0030.46O

Atom 15367N LEU B467-52.333-37.506-44.7261.0029.59N

Atom 15368 CA LEU B467-51.953-38.540-43.7691.0029.19C

Atom 15370 CB LEU B467-51.640-39.869-44.4761.0029.27C

Atom 15373 CG LEU B467-50.356-40.081-45.2681.0029.84C

Atom 15375 CD1 LEU B467-49.341-40.761-44.3571.0031.06C

Atom 15379 CD2 LEU B467-50.589-40.920-46.5231.0029.47C

Atom 15383C LEU B467-50.865-38.092-42.7941.0028.54C

Atom 15384O LEU B467-50.490-38.834-41.8941.0028.28O

Atom 15386N ALA B468-50.388-36.862-42.9621.0028.04N

Atom 15387 CA ALA B468-49.682-36.158-41.8931.0027.54C

Atom 15389 CB ALA B468-48.922-34.970-42.4351.0027.34C

Atom 15393C ALA B468-50.711-35.698-40.8651.0027.17C

Atom 15394O ALA B468-50.482-35.801-39.6621.0027.40O

Atom 15396N THR B469-51.841-35.182-41.3491.0026.57N

Atom 15397 CA THR B469-52.957-34.795-40.4901.0025.87C

Atom 15399 CB THR B469-54.130-34.297-41.3281.0025.53C

Atom 15401 OG1 THR B469-53.737-33.111-42.0251.0024.99O

Atom 15403 CG2 THR B469-55.316-33.993-40.4531.0024.62C

Atom 15407C THR B469-53.412-35.988-39.6691.0025.95C

Atom 15408O THR B469-53.551-35.925-38.4501.0025.80O

Atom 15410N GLU B470-53.618-37.091-40.3671.0026.06N

Atom 15411 CA GLU B470-54.043-38.344-39.7561.0026.10C

Atom 15413 CB GLU B470-54.057-39.436-40.8481.0026.60C

Atom 15416 CG GLU B470-55.038-40.587-40.6461.0028.01C

Atom 15419 CD GLU B470-54.553-41.897-41.2861.0029.05C

Atom 15420 OE1 GLU B470-54.298-41.930-42.5151.0027.96O

Atom 15421 OE2 GLU B470-54.435-42.892-40.5361.0030.42O

Atoms 15422C GLU B470-53.148-38.746-38.5571.0025.28C

Atom 15423O GLU B470-53.629-39.266-37.5561.0025.08O

Atom 15425N SER B471-51.850-38.497-38.6541.0024.70N

Atom 15426 CA SER B471-50.930-38.906-37.5991.0024.26C

Atom 15428 CB SER B471-49.494-38.842-38.0851.0024.11C

Atom 15431 OG SER B471-49.315-39.693-39.1861.0023.98O

Atom 15433C SER B471-51.085-38.029-36.3771.0023.92C

Atom 15434O SER B471-51.240-38.530-35.2701.0024.09O

Atom 15436N VAL B472-51.032-36.719-36.5821.0023.48N

Atom 15437 CA VAL B472-51.279-35.774-35.5101.0023.15C

Atom 15439 CB VAL B472-51.377-34.332-36.0451.0023.03C

Atom 15441 CG1 VAL B472-51.739-33.347-34.9291.0021.74C

Atom 15445 CG2 VAL B472-50.067-33.945-36.7281.0022.27C

Atom 15449C VAL B472-52.572-36.192-34.8301.0023.49C

Atom 15450O VAL B472-52.663-36.276-33.6141.0023.29O

Atom 15452N MET B473-53.573-36.508-35.6261.0024.34N

Atom 15453 CA MET B473-54.850-36.901-35.0701.0024.93C

Atom 15455 CB MET B473-55.816-37.266-36.1901.0025.09C

Atom 15458 CG MET B473-57.191-36.788-35.9121.0026.94C

Atom 15461 SD MET B473-57.328-35.035-36.2511.0029.69S

Atom 15462 CE MET B473-58.316-35.080-37.7751.0029.12C

Atom 15466C MET B473-54.668-38.072-34.1001.0025.00C

Atom 15467O MET B473-55.135-38.018-32.9631.0024.78O

Atom 15469N ASN B474-53.965-39.110-34.5561.0025.30N

Atom 15470 CA ASN B474-53.681-40.293-33.7381.0025.55C

Atom 15472 CB ASN B474-53.143-41.439-34.6011.0025.82C

Atom 15475 CG ASN B474-54.243-42.137-35.4021.0027.62C

Atom 15476 OD1 ASN B474-54.238-42.102-36.6381.0029.33O

Atom 15477 ND2 ASN B474-55.196-42.780-34.6971.0028.58N

Atoms 15480C ASN B474-52.711-40.034-32.5921.0025.20C

Atom 15481O ASN B474-52.711-40.773-31.6211.0025.71O

Atom 15483N LEU B475-51.883-38.999-32.7041.0024.65N

Atom 15484 CA LEU B475-50.987-38.595-31.6141.0024.04C

Atoms 15486 CB LEU B475-49.939-37.626-32.1421.0023.88C

Atoms 15489 CG LEU B475-48.837-37.285-31.1641.0023.70C

Atom 15491 CD1 LEU B475-47.936-38.471-31.0041.0023.97C

Atom 15495 CD2 LEU B475-48.088-36.104-31.6791.0023.99C

Atom 15499C LEU B475-51.747-37.940-30.4531.0023.65C

Atom 15500O LEU B475-51.323-38.014-29.2991.0023.74O

Atom 15502N ILE B476-52.858-37.282-30.7661.0023.15N

Atom 15503 CA ILE B476-53.728-36.711-29.7421.0022.50C

Atom 15505 CB ILE B476-54.779-35.755-30.3591.0022.27C

Atom 15507 CG1 ILE B476-54.099-34.508-30.9101.0020.55C

Atom 15510 CD1 ILE B476-55.000-33.671-31.6931.0019.19C

Atom 15514 CG2 ILE B476-55.817-35.363-29.3361.0022.15C

Atom 15518C ILE B476-54.398-37.849-28.9851.0022.40C

Atom 15519O ILE B476-54.316-37.900-27.7671.0022.32O

Atom 15521N ASP B477-55.023-38.777-29.7081.0022.37N

Atom 15522 CA ASP B477-55.616-39.975-29.0901.0022.55C

Atom 15524 CB ASP B477-55.996-41.007-30.1511.0022.67C

Atom 15527 CG ASP B477-57.262-40.636-30.8921.0024.93C

Atom 15528 OD1 ASP B477-57.690-39.458-30.8181.0028.87O

Atom 15529 OD2 ASP B477-57.847-41.523-31.5491.0027.92O

Atom 15530C ASP B477-54.675-40.622-28.0831.0022.10C

Atom 15531O ASP B477-55.048-40.877-26.9381.0021.83O

Atom 15533N GLU B478-53.444-40.867-28.5101.0021.73N

Atom 15534 CA GLU B478-52.472-41.506-27.6451.0021.69C

Atom 15536 CB GLU B478-51.233-41.920-28.4371.0021.97C

Atom 15539 CG GLU B478-50.786-43.360-28.1501.0024.18C

Atom 15542 CD GLU B478-51.793-44.429-28.6181.0027.03C

Atom 15543 OE1 GLU B478-51.599-45.627-28.2851.0029.15O

Atom 15544 OE2 GLU B478-52.770-44.080-29.3231.0028.37O

Atom 15545C GLU B478-52.107-40.608-26.4491.0020.97C

Atom 15546O GLU B478-51.928-41.110-25.3161.0021.15O

Atom 15548N THR B479-52.031-39.291-26.6871.0019.82N

Atom 15549 CA THR B479-51.787-38.319-25.6041.0018.59C

Atom 15551 CB THR B479-51.587-36.897-26.1291.0017.95C

Atom 15553 OG1 THR B479-50.291-36.779-26.7121.0017.43O

Atom 15555 CG2 THR B479-51.654-35.938-25.0091.0017.90C

Atom 15559C THR B479-52.927-38.342-24.5801.0018.16C

Atom 15560O THR B479-52.695-38.339-23.3831.0018.06O

Atom 15562N TRP B480-54.160-38.390-25.0571.0017.77N

Atom 15563 CA TRP B480-55.301-38.493-24.1691.0017.54C

Atom 15565 CB TRP B480-56.605-38.464-24.9701.0017.49C

Atom 15568 CG TRP B480-57.239-37.099-25.0281.0017.53C

Atom 15569 CD1 TRP B480-57.150-36.186-26.0411.0017.04C

Atom 15571 NE1 TRP B480-57.857-35.067-25.7211.0016.57N

Atom 15573 CE2 TRP B480-58.423-35.236-24.4841.0016.41C

Atom 15574 CD2 TRP B480-58.055-36.498-24.0201.0016.68C

Atom 15575 CE3 TRP B480-58.507-36.914-22.7651.0016.92C

Atom 15577 CZ3 TRP B480-59.300-36.076-22.0391.0016.97C

Atom 15579 CH2 TRP B480-59.654-34.823-22.5241.0016.91C

Atom 15581 CZ2 TRP B480-59.223-34.383-23.7421.0016.89C

Atom 15583C TRP B480-55.232-39.760-23.3341.0017.75C

Atom 15584O TRP B480-55.582-39.747-22.1641.0017.74O

Atom 15586N LYS B481-54.784-40.861-23.9331.0018.09N

Atom 15587 CA LYS B481-54.721-42.124-23.2101.0018.10C

Atom 15589 CB LYS B481-54.277-43.282-24.1151.0018.01C

Atom 15592 CG LYS B481-55.311-43.803-25.1141.0016.89C

Atom 15595 CD LYS B481-54.613-44.663-26.1991.0015.83C

Atom 15598 CE LYS B481-55.587-45.500-27.0251.0014.74C

Atoms 15601 NZ LYS B481-55.119-45.725-28.4131.0012.34N

Atom 15605C LYS B481-53.750-41.970-22.0541.0018.46C

Atom 15606O LYS B481-53.976-42.494-20.9691.0018.44O

Atoms 15608N LYS B482-52.662-41.252-22.2791.0018.80N

Atom 15609 CA LYS B482-51.727-41.019-21.1921.0019.58C

Atom 15611 CB LYS B482-50.425-40.424-21.7271.0020.03C

Atom 15614 CG LYS B482-49.499-41.500-22.2771.0022.03C

Atom 15617 CD LYS B482-48.706-41.063-23.5061.0024.87C

Atom 15620 CE LYS B482-47.908-42.268-24.0661.0026.65C

Atoms 15623 NZ LYS B482-47.287-41.996-25.4081.0028.80N

Atom 15627C LYS B482-52.363-40.156-20.0961.0019.56C

Atom 15628O LYS B482-52.367-40.537-18.9261.0019.19O

Atom 15630N MET B483-52.922-39.013-20.4831.0020.00N

Atom 15631 CA MET B483-53.677-38.165-19.5521.0020.37C

Atom 15633 CB MET B483-54.426-37.057-20.2951.0020.25C

Atom 15636 CG MET B483-53.529-35.951-20.8071.0020.52C

Atom 15639 SD MET B483-54.461-34.483-21.2251.0020.47S

Atom 15640 CE MET B483-55.361-35.084-22.6491.0022.07C

Atom 15644C MET B483-54.668-38.981-18.7411.0020.72C

Atom 15645O MET B483-54.809-38.779-17.5431.0020.37O

Atom 15647N ASN B484-55.345-39.910-19.4031.0021.57N

Atom 15648 CA ASN B484-56.339-40.731-18.7441.0022.46C

Atom 15650 CB ASN B484-57.042-41.631-19.7651.0022.23C

Atom 15653 CG ASN B484-58.118-40.900-20.5761.0021.61C

Atom 15654 OD1 ASN B484-58.412-39.722-20.3621.0020.25O

Atom 15655 ND2 ASN B484-58.720-41.622-21.5101.0020.80N

Atom 15658C ASN B484-55.723-41.555-17.5981.0023.83C

Atom 15659O ASN B484-56.262-41.591-16.4841.0023.76O

Atom 15661N LYS B485-54.585-42.190-17.8681.0025.69N

Atom 15662 CA LYS B485-53.854-42.937-16.8431.0027.11C

Atom 15664 CB LYS B485-52.679-43.712-17.4471.0027.13C

Atom 15667 CG LYS B485-52.073-44.755-16.4891.0028.85C

Atom 15670 CD LYS B485-51.643-46.082-17.1871.0031.17C

Atom 15673 CE LYS B485-50.150-46.132-17.5551.0032.11C

Atoms 15676 NZ LYS B485-49.291-46.282-16.3441.0033.08N

Atoms 15680C LYS B485-53.370-42.035-15.7011.0028.37C

Atom 15681O LYS B485-53.288-42.481-14.5631.0028.59O

Atom 15683N GLU B486-53.083-40.766-15.9801.0029.89N

Atom 15684 CA GLU B486-52.683-39.849-14.9101.0031.09C

Atom 15686 CB GLU B486-52.174-38.511-15.4701.0031.55C

Atom 15689 CG GLU B486-51.059-37.851-14.6431.0032.69C

Atom 15692 CD GLU B486-49.785-38.689-14.6051.0034.51C

Atom 15693 OE1 GLU B486-49.104-38.682-13.5571.0036.35O

Atom 15694 OE2 GLU B486-49.476-39.368-15.6111.0034.55O

Atoms 15695C GLU B486-53.836-39.615-13.9391.0031.70C

Atom 15696O GLU B486-53.684-39.868-12.7501.0031.90O

Atoms 15698N LYS B487-54.983-39.164-14.4531.0032.71N

Atom 15699 CA LYS B487-56.177-38.856-13.6291.0033.57C

Atom 15701 CB LYS B487-57.343-38.402-14.5191.0033.54C

Atom 15704 CG LYS B487-58.703-38.196-13.8231.0033.45C

Atom 15707 CD LYS B487-58.686-37.024-12.8661.0033.71C

Atoms 15710 CE LYS B487-59.906-36.996-11.9311.0034.48C

Atoms 15713 NZ LYS B487-61.123-36.378-12.5261.0035.03N

Atom 15717C LYS B487-56.626-40.046-12.8021.0034.60C

Atom 15718O LYS B487-57.126-39.892-11.6811.0034.55O

Atom 15720N LEU B488-56.453-41.233-13.3711.0035.94N

Atom 15721 CA LEU B488-56.878-42.451-12.7231.0037.00C

Atom 15723 CB LEU B488-57.280-43.489-13.7781.0036.90C

Atom 15726 CG LEU B488-58.081-44.714-13.3121.0037.52C

Atom 15728 CD1 LEU B488-58.758-44.536-11.9461.0038.76C

Atom 15732 CD2 LEU B488-59.121-45.084-14.3461.0038.42C

Atom 15736C LEU B488-55.786-42.980-11.8031.0038.02C

Atom 15737O LEU B488-56.063-43.315-10.6531.0038.19O

Atom 15739N GLY B489-54.550-43.016-12.2981.0039.44N

Atom 15740 CA GLY B489-53.441-43.710-11.6211.0040.62C

Atom 15743C GLY B489-52.563-42.837-10.7401.0041.76C

Atom 15744O GLY B489-51.357-42.703-10.9881.0041.83O

Atom 15746N GLY B490-53.183-42.230-9.7261.0043.10N

Atom 15747 CA GLY B490-52.481-41.538-8.6361.0043.82C

Atom 15750C GLY B490-51.131-40.924-8.9671.0044.31C

Atom 15751O GLY B490-50.084-41.560-8.8311.0044.25O

Atom 15753N SER B491-51.161-39.672-9.3961.0044.87N

Atom 15754 CA SER B491-49.939-38.892-9.5751.0045.22C

Atom 15756 CB SER B491-50.224-37.723-10.5371.0045.34C

Atom 15759 OG SER B491-51.411-37.032-10.1661.0045.38O

Atom 15761C SER B491-49.419-38.389-8.2031.0045.14C

Atom 15762O SER B491-49.896-38.824-7.1401.0045.11O

Atom 15764N LEU B492-48.429-37.491-8.2271.0044.77N

Atom 15765 CA LEU B492-48.046-36.752-7.0181.0044.31C

Atom 15767 CB LEU B492-46.726-35.971-7.1881.0044.55C

Atom 15770 CG LEU B492-45.530-36.546-7.9721.0045.73C

Atom 15772 CD1 LEU B492-44.373-35.556-7.8591.0046.25C

Atom 15776 CD2 LEU B492-45.084-37.972-7.5301.0046.14C

Atoms 15780C LEU B492-49.151-35.760-6.7031.0043.30C

Atom 15781O LEU B492-49.315-35.370-5.5551.0043.49O

Atom 15783N PHE B493-49.903-35.367-7.7351.0042.05N

Atom 15784 CA PHE B493-50.822-34.239-7.6681.0041.03C

Atom 15786 CB PHE B493-50.913-33.549-9.0281.0040.81C

Atom 15789 CG PHE B493-49.696-32.771-9.4081.0038.96C

Atom 15790 CD1 PHE B493-49.651-31.408-9.2331.0037.06C

Atom 15792 CE1 PHE B493-48.543-30.697-9.6031.0036.41C

Atom 15794 CZ PHE B493-47.471-31.341-10.1581.0035.87C

Atom 15796 CE2 PHE B493-47.507-32.690-10.3431.0036.39C

Atom 15798 CD2 PHE B493-48.612-33.400-9.9771.0037.36C

Atom 15800C PHE B493-52.240-34.603-7.2681.0040.76C

Atom 15801O PHE B493-52.686-35.733-7.4191.0040.35O

Atom 15803N ALA B494-52.943-33.584-6.7901.0040.72N

Atom 15804 CA ALA B494-54.355-33.658-6.4711.0040.68C

Atom 15806 CB ALA B494-54.786-32.362-5.7701.0040.70C

Atom 15810C ALA B494-55.175-33.851-7.7441.0040.59C

Atom 15811O ALA B494-55.013-33.099-8.7161.0040.95O

Atom 15813N LYS B495-56.071-34.835-7.7331.0040.12N

Atom 15814 CA LYS B495-57.000-35.047-8.8541.0039.67C

Atoms 15816 CB LYS B495-58.008-36.166-8.5201.0039.98C

Atom 15819 CG LYS B495-57.388-37.590-8.4961.0040.57C

Atom 15822 CD LYS B495-58.468-38.688-8.4191.0041.18C

Atom 15825 CE LYS B495-57.878-40.065-8.1321.0041.28C

Atom 15828 NZ LYS B495-58.736-41.159-8.6711.0041.39N

Atom 15832C LYS B495-57.717-33.752-9.3331.0038.82C

Atom 15833O LYS B495-57.847-33.535-10.5371.0038.70O

Atom 15835N PRO B496-58.169-32.890-8.3971.0037.71N

Atom 15836 CA PRO B496-58.701-31.551-8.6871.0036.80C

Atom 15838 CB PRO B496-58.820-30.937-7.3041.0036.94C

Atom 15841 CG PRO B496-59.255-32.073-6.4831.0037.90C

Atom 15844 CD PRO B496-58.534-33.294-7.0301.0037.86C

Atom 15847C PRO B496-57.845-30.625-9.5361.0035.57C

Atom 15848O PRO B496-58.389-29.693-10.1391.0035.93O

Atom 15849N PHE B497-56.527-30.836-9.5461.0033.52N

Atom 15850 CA PHE B497-55.654-30.083-10.4391.0031.34C

Atom 15852 CB PHE B497-54.355-29.710-9.7501.0030.86C

Atom 15855 CG PHE B497-53.394-28.989-10.6341.0029.04C

Atom 15856 CD1 PHE B497-53.639-27.700-11.0221.0027.89C

Atom 15858 CE1 PHE B497-52.752-27.028-11.8341.0027.39C

Atom 15860 CZ PHE B497-51.599-27.653-12.2591.0027.40C

Atom 15862 CE2 PHE B497-51.341-28.941-11.8771.0027.44C

Atom 15864 CD2 PHE B497-52.236-29.604-11.0741.0028.18C

Atom 15866C PHE B497-55.390-30.870-11.7141.0030.24C

Atom 15867O PHE B497-55.301-30.266-12.7861.0030.39O

Atom 15869N VAL B498-55.295-32.200-11.6301.0028.50N

Atom 15870 CA VAL B498-55.076-32.983-12.8541.0027.54C

Atom 15872 CB VAL B498-54.778-34.472-12.6111.0027.34C

Atom 15874 CG1 VAL B498-56.027-35.194-12.2621.0028.14C

Atom 15878 CG2 VAL B498-53.731-34.649-11.5301.0027.04C

Atom 15882C VAL B498-56.277-32.857-13.7841.0026.60C

Atom 15883O VAL B498-56.129-32.864-14.9951.0026.33O

Atom 15885N GLU B499-57.468-32.731-13.2141.0025.87N

Atom 15886 CA GLU B499-58.662-32.484-14.0221.0025.20C

Atom 15888 CB GLU B499-59.975-32.639-13.2061.0025.26C

Atom 15891 CG GLU B499-61.287-32.694-14.0281.0025.16C

Atom 15894 CD GLU B499-61.422-33.922-14.9731.0026.79C

Atom 15895 OE1 GLU B499-60.607-34.880-14.9281.0026.39O

Atom 15896 OE2 GLU B499-62.379-33.926-15.7851.0027.83O

Atom 15897C GLU B499-58.542-31.097-14.6411.0024.27C

Atom 15898O GLU B499-58.819-30.948-15.8321.0024.32O

Atom 15900N THR B500-58.098-30.093-13.8821.0022.90N

Atom 15901 CA THR B500-58.027-28.764-14.4871.0022.29C

Atom 15903 CB THR B500-57.908-27.592-13.4881.0022.43C

Atom 15905 OG1 THR B500-56.536-27.259-13.2741.0022.65O

Atom 15907 CG2 THR B500-58.614-27.899-12.1831.0022.84C

Atom 15911C THR B500-56.940-28.671-15.5651.0021.20C

Atom 15912O THR B500-57.120-27.939-16.5361.0021.06O

Atom 15914N ALA B501-55.845-29.414-15.4221.0019.88N

Atom 15915 CA ALA B501-54.906-29.574-16.5371.0019.24C

Atom 15917 CB ALA B501-53.704-30.393-16.1151.0019.22C

Atom 15921C ALA B501-55.581-30.226-17.7571.0018.68C

Atom 15922O ALA B501-55.427-29.768-18.8811.0018.32O

Atom 15924N ILE B502-56.324-31.300-17.5231.0018.11N

Atom 15925 CA ILE B502-57.023-31.988-18.5911.0017.68C

Atom 15927 CB ILE B502-57.750-33.251-18.0591.0017.63C

Atom 15929 CG1 ILE B502-56.713-34.350-17.7691.0018.16C

Atom 15932 CD1 ILE B502-57.253-35.645-17.1151.0017.02C

Atom 15936 CG2 ILE B502-58.756-33.762-19.0631.0016.93C

Atom 15940C ILE B502-57.990-31.030-19.2891.0017.50C

Atom 15941O ILE B502-58.153-31.071-20.5121.0017.62O

Atom 15943N ASN B503-58.604-30.139-18.5241.0017.23N

Atom 15944 CA ASN B503-59.545-29.184-19.1021.0017.07C

Atom 15946 CB ASN B503-60.184-28.327-18.0161.0017.21C

Atom 15949 CG ASN B503-61.155-29.094-17.1761.0017.29C

Atom 15950 OD1 ASN B503-61.721-30.097-17.6091.0016.66O

Atom 15951 ND2 ASN B503-61.365-28.621-15.9581.0019.16N

Atom 15954C ASN B503-58.920-28.270-20.1491.0016.59C

Atom 15955O ASN B503-59.611-27.811-21.0711.0016.67O

Atom 15957N LEU B504-57.629-27.992-20.0141.0015.79N

Atom 15958 CA LEU B504-56.948-27.204-21.0311.0015.44C

Atom 15960 CB LEU B504-55.530-26.865-20.6091.0015.07C

Atom 15963 CG LEU B504-54.933-25.837-21.5521.0014.21C

Atom 15965 CD1 LEU B504-54.246-24.726-20.8001.0014.21C

Atom 15969 CD2 LEU B504-54.000-26.538-22.4621.0014.27C

Atom 15973C LEU B504-56.954-27.933-22.3751.0015.59C

Atom 15974O LEU B504-57.177-27.323-23.4141.0015.30O

Atom 15976N ALA B505-56.732-29.242-22.3411.0015.89N

Atom 15977 CA ALA B505-56.914-30.073-23.5141.0016.23C

Atom 15979 CB ALA B505-56.608-31.483-23.1881.0016.05C

Atom 15983C ALA B505-58.352-29.955-24.0101.0016.69C

Atom 15984O ALA B505-58.598-29.738-25.2041.0016.88O

Atom 15986N ARG B506-59.300-30.071-23.0901.0016.88N

Atom 15987 CA ARG B506-60.709-29.972-23.4571.0017.20C

Atom 15989 CB ARG B506-61.630-30.170-22.2481.0017.34C

Atom 15992 CG ARG B506-61.549-31.537-21.6141.0017.46C

Atom 15995 CD ARG B506-62.837-31.917-20.9621.0017.48C

Atom 15998 NE ARG B506-62.783-33.280-20.4351.0018.37N

Atom 16000 CZ ARG B506-62.404-33.613-19.2011.0019.03C

Atom 16001 NH1 ARG B506-62.008-32.690-18.3241.0018.83N

Atom 16004 NH2 ARG B506-62.415-34.892-18.8411.0019.72N

Atom 16007C ARG B506-61.038-28.646-24.1141.0017.32C

Atom 16008O ARG B506-61.754-28.622-25.1111.0017.41O

Atom 16010N GLN B507-60.540-27.543-23.5641.0017.59N

Atom 16011 CA GLN B507-60.864-26.233-24.1391.0018.05C

Atom 16013 CB GLN B507-60.382-25.090-23.2581.0018.16C

Atom 16016 CG GLN B507-60.798-23.709-23.7641.0017.57C

Atom 16019 CD GLN B507-62.291-23.508-23.7231.0017.42C

Atom 16020 OE1 GLN B507-62.953-23.959-22.8001.0017.55O

Atom 16021 NE2 GLN B507-62.832-22.823-24.7221.0017.56N

Atom 16024C GLN B507-60.258-26.060-25.5211.0018.49C

Atom 16025O GLN B507-60.855-25.413-26.3801.0018.73O

Atom 16027N SER B508-59.066-26.619-25.7241.0018.85N

Atom 16028 CA SER B508-58.427-26.621-27.0371.0019.07C

Atom 16030 CB SER B508-57.108-27.364-26.9691.0019.04C

Atom 16033 OG SER B508-56.304-26.772-25.9791.0020.10O

Atom 16035C SER B508-59.305-27.296-28.0651.0019.12C

Atom 16036O SER B508-59.438-26.827-29.1871.0019.00O

Atom 16038N HIS B509-59.905-28.409-27.6741.0019.26N

Atom 16039 CA HIS B509-60.814-29.095-28.5591.0019.33C

Atom 16041 CB HIS B509-61.275-30.412-27.9591.0019.30C

Atom 16044 CG HIS B509-60.263-31.501-28.0671.0018.71C

Atom 16045 ND1 HIS B509-59.941-32.089-29.2671.0018.57N

Atom 16047 CE1 HIS B509-59.020-33.012-29.0641.0019.07C

Atom 16049 NE2 HIS B509-58.738-33.044-27.7741.0018.52N

Atom 16051 CD2 HIS B509-59.499-32.105-27.1291.0018.43C

Atom 16053C HIS B509-62.017-28.251-28.8781.0019.60C

Atom 16054O HIS B509-62.491-28.286-29.9691.0019.68O

Atom 16056N CYS B510-62.540-27.502-27.9321.0020.12N

Atom 16057 CA CYS B510-63.748-26.738-28.2161.0020.63C

Atom 16059 CB CYS B510-64.493-26.492-26.9151.0020.70C

Atom 16062 SG CYS B510-64.856-28.020-26.0651.0022.93S

Atom 16064C CYS B510-63.465-25.422-28.9501.0020.55C

Atom 16065O CYS B510-64.338-24.881-29.6221.0020.16O

Atom 16067N THR B511-62.236-24.933-28.8271.0020.89N

Atom 16068 CA THR B511-61.833-23.654-29.3781.0021.32C

Atom 16070 CB THR B511-60.682-23.107-28.5501.0020.76C

Atom 16072 OG1 THR B511-61.208-22.619-27.3241.0019.50O

Atom 16074 CG2 THR B511-59.961-21.994-29.2531.0019.79C

Atom 16078C THR B511-61.417-23.735-30.8511.0023.11C

Atom 16079O THR B511-61.910-22.992-31.6941.0022.75O

Atom 16081N TYR B512-60.501-24.646-31.1521.0025.46N

Atom 16082 CA TYR B512-59.867-24.704-32.4621.0027.09C

Atom 16084 CB TYR B512-58.397-25.107-32.3271.0027.16C

Atom 16087 CG TYR B512-57.598-24.056-31.5821.0027.26C

Atom 16088 CD1 TYR B512-57.300-22.834-32.1821.0028.18C

Atom 16090 CE1 TYR B512-56.583-21.844-31.5111.0027.98C

Atom 16092 CZ TYR B512-56.164-22.068-30.2261.0027.72C

Atom 16093 OH TYR B512-55.462-21.072-29.5841.0027.09O

Atom 16095 CE2 TYR B512-56.453-23.281-29.6021.0027.52C

Atom 16097 CD2 TYR B512-57.171-24.262-30.2781.0026.68C

Atom 16099C TYR B512-60.633-25.623-33.3821.0028.79C

Atom 16100O TYR B512-61.050-25.179-34.4441.0028.98O

Atom 16102N HIS B513-60.789-26.893-32.9911.0031.06N

Atom 16103 CA HIS B513-61.865-27.800-33.4921.0033.07C

Atom 16105 CB HIS B513-62.740-28.208-32.2651.0033.66C

Atom 16108 CG HIS B513-64.181-28.602-32.5351.0034.73C

Atom 16109 ND1 HIS B513-65.035-27.903-33.3671.0035.70N

Atom 16111 CE1 HIS B513-66.234-28.464-33.3431.0035.40C

Atom 16113 NE2 HIS B513-66.206-29.469-32.4911.0035.10N

Atom 16115 CD2 HIS B513-64.943-29.565-31.9561.0035.07C

Atom 16117C HIS B513-62.692-27.179-34.6231.0034.03C

Atom 16118O HIS B513-63.003-27.848-35.6271.0034.55O

Atom 16120N ASN B514-63.047-25.906-34.4441.0034.65N

Atom 16121 CA ASN B514-63.713-25.123-35.4831.0035.15C

Atom 16123 CB ASN B514-63.845-23.643-35.0701.0035.01C

Atom 16126 CG ASN B514-64.704-23.456-33.8201.0033.48C

Atom 16127 OD1 ASN B514-64.787-24.343-32.9681.0030.92O

Atom 16128 ND2 ASN B514-65.327-22.295-33.7031.0032.16N

Atom 16131C ASN B514-63.192-25.274-36.9421.0036.08C

Atom 16132O ASN B514-62.010-25.051-37.2541.0035.69O

Atom 16134N GLY B515-64.119-25.765-37.7721.0037.15N

Atom 16135 CA GLY B515-64.224-25.493-39.1771.0037.94C

Atom 16138C GLY B515-65.269-24.384-39.2841.0039.01C

Atom 16139O GLY B515-64.904-23.286-39.7021.0039.58O

Atom 16141N ASP B516-66.550-24.585-38.9091.0039.95N

Atom 16142 CA ASP B516-67.167-25.810-38.3491.0040.65C

Atom 16144 CB ASP B516-67.296-25.652-36.8361.0041.09C

Atom 16147 CG ASP B516-66.318-26.511-36.0631.0043.63C

Atom 16148 OD1 ASP B516-65.697-27.434-36.6621.0045.83O

Atom 16149 OD2 ASP B516-66.152-26.246-34.8431.0047.12O

Atom 16150C ASP B516-68.603-26.067-38.8531.0040.78C

Atom 16151O ASP B516-69.134-25.301-39.6601.0041.28O

Atom 16153N ALA B517-69.222-27.141-38.3491.0040.66N

Atom 16154 CA ALA B517-70.675-27.396-38.4681.0040.60C

Atom 16156 CB ALA B517-71.422-26.622-37.3591.0040.27C

Atom 16160C ALA B517-71.295-27.106-39.8621.0040.79C

Atom 16161O ALA B517-70.654-27.296-40.8991.0040.67O

Atom 16163N HIS B518-72.562-26.696-39.8741.0041.13N

Atom 16164 CA HIS B518-73.162-26.033-41.0391.0041.60C

Atom 16166 CB HIS B518-74.446-26.756-41.4801.0042.24C

Atom 16169 CG HIS B518-74.207-28.179-41.9101.0045.54C

Atom 16170 ND1 HIS B518-73.441-28.509-43.0121.0048.51N

Atom 16172 CE1 HIS B518-73.392-29.825-43.1401.0048.79C

Atom 16174 NE2 HIS B518-74.092-30.364-42.1561.0049.12N

Atom 16176 CD2 HIS B518-74.608-29.357-41.3691.0048.28C

Atom 16178C HIS B518-73.377-24.545-40.6861.0040.84C

Atom 16179O HIS B518-74.487-23.997-40.7691.0040.60O

Atom 16181N THR B519-72.261-23.932-40.2751.0040.10N

Atom 16182 CA THR B519-72.143-22.521-39.8781.0039.39C

Atom 16184 CB THR B519-72.561-22.263-38.3931.0039.40C

Atom 16186 OG1 THR B519-71.823-23.131-37.5171.0039.55O

Atom 16188 CG2 THR B519-74.074-22.460-38.1781.0038.98C

Atom 16192C THR B519-70.654-22.164-40.0591.0038.81C

Atom 16193O THR B519-69.800-23.050-40.0671.0038.48O

Atom 16195N SER B520-70.338-20.881-40.1991.0038.19N

Atom 16196 CA SER B520-68.959-20.453-40.5211.0037.77C

Atom 16198 CB SER B520-68.983-18.976-40.9601.0037.76C

Atom 16201 OG SER B520-68.760-18.106-39.8701.0038.49O

Atom 16203C SER B520-67.974-20.724-39.3401.0037.24C

Atom 16204O SER B520-68.394-21.267-38.3201.0036.89O

Atom 16206N PRO B521-66.671-20.350-39.4721.0036.96N

Atom 16207 CA PRO B521-65.692-20.638-38.3961.0036.80C

Atom 16209 CB PRO B521-64.320-20.354-39.0411.0036.68C

Atom 16212 CG PRO B521-64.599-19.593-40.3091.0037.19C

Atom 16215 CD PRO B521-66.091-19.469-40.5071.0037.10C

Atom 16218C PRO B521-65.915-19.763-37.1681.0036.68C

Atom 16219O PRO B521-66.233-20.289-36.1051.0036.90O

Atom 16220N ASP B522-65.744-18.445-37.2981.0036.61N

Atom 16221 CA ASP B522-66.373-17.528-36.3471.0036.58C

Atom 16223 CB ASP B522-65.938-16.070-36.5431.0036.82C

Atom 16226 CG ASP B522-64.456-15.846-36.2431.0037.94C

Atom 16227 OD1 ASP B522-63.848-16.627-35.4731.0039.62O

Atom 16228 OD2 ASP B522-63.891-14.876-36.7901.0039.40O

Atom 16229C ASP B522-67.836-17.718-36.6811.0036.12C

Atom 16230O ASP B522-68.150-18.306-37.7021.0035.98O

Atom 16232N GLU B523-68.732-17.249-35.8301.0035.69N

Atom 16233 CA GLU B523-70.152-17.605-35.9271.0035.46C

Atom 16235 CB GLU B523-70.703-17.560-37.3791.0035.51C

Atom 16238 CG GLU B523-70.535-16.175-38.0611.0036.11C

Atom 16241 CD GLU B523-70.854-16.136-39.5721.0036.72C

Atom 16242 OE1 GLU B523-71.848-16.767-40.0131.0037.20O

Atom 16243 OE2 GLU B523-70.101-15.452-40.3141.0035.53O

Atom 16244C GLU B523-70.440-18.943-35.2161.0034.97C

Atom 16245O GLU B523-71.557-19.148-34.7651.0035.02O

Atoms 16247N LEU B524-69.462-19.846-35.0991.0034.59N

Atom 16248 CA LEU B524-69.503-20.832-34.0041.0034.45C

Atom 16250 CB LEU B524-68.735-22.136-34.2861.0034.21C

Atom 16253 CG LEU B524-69.530-23.434-34.5081.0033.92C

Atoms 16255 CD1 LEU B524-68.657-24.627-34.2271.0032.21C

Atoms 16259 CD2 LEU B524-70.794-23.520-33.6411.0034.06C

Atoms 16263C LEU B524-68.901-20.162-32.7911.0034.38C

Atom 16264O LEU B524-69.535-20.067-31.7411.0034.49O

Atom 16266N THR B525-67.670-19.688-32.9581.0034.30N

Atom 16267 CA THR B525-66.913-19.073-31.8741.0034.23C

Atom 16269 CB THR B525-65.570-18.524-32.3801.0034.04C

Atom 16271 OG1 THR B525-64.894-19.549-33.1121.0033.83O

Atom 16273 CG2 THR B525-64.689-18.087-31.2271.0033.37C

Atom 16277C THR B525-67.702-17.960-31.1841.0034.46C

Atom 16278O THR B525-67.684-17.858-29.9551.0034.57O

Atom 16280N ARG B526-68.401-17.144-31.9691.0034.54N

Atom 16281 CA ARG B526-69.200-16.056-31.4181.0034.60C

Atom 16283 CB ARG B526-69.571-15.059-32.5131.0035.04C

Atom 16286 CG ARG B526-70.256-13.800-32.0131.0037.13C

Atom 16289 CD ARG B526-70.143-12.656-33.0261.0039.87C

Atom 16292 NE ARG B526-70.353-13.075-34.4201.0042.28N

Atom 16294 CZ ARG B526-71.543-13.292-35.0001.0044.26C

Atom 16295 NH1 ARG B526-72.685-13.159-34.3201.0044.66N

Atom 16298 NH2 ARG B526-71.593-13.658-36.2791.0044.49N

Atom 16301C ARG B526-70.448-16.593-30.7351.0033.91C

Atom 16302O ARG B526-70.848-16.074-29.7041.0033.74O

Atom 16304N LYS B527-71.048-17.637-31.3061.0033.39N

Atom 16305 CA LYS B527-72.240-18.252-30.7221.0033.15C

Atom 16307 CB LYS B527-72.837-19.332-31.6391.0033.42C

Atom 16310 CG LYS B527-73.898-18.804-32.6091.0034.55C

Atom 16313 CD LYS B527-74.643-19.919-33.3581.0035.43C

Atom 16316 CE LYS B527-75.230-19.383-34.6671.0036.11C

Atoms 16319 NZ LYS B527-76.076-20.372-35.3841.0037.04N

Atom 16323C LYS B527-71.925-18.865-29.3781.0032.36C

Atom 16324O LYS B527-72.589-18.584-28.3871.0032.56O

Atom 16326N ARG B528-70.909-19.713-29.3581.0031.53N

Atom 16327 CA ARG B528-70.502-20.401-28.1381.0030.77C

Atom 16329 CB ARG B528-69.283-21.286-28.4141.0030.55C

Atom 16332 CG ARG B528-69.624-22.519-29.2521.0029.48C

Atom 16335 CD ARG B528-68.418-23.417-29.4931.0028.05C

Atom 16338 NE ARG B528-68.811-24.774-29.8801.0026.55N

Atom 16340 CZ ARG B528-67.968-25.719-30.2881.0025.87C

Atom 16341 NH1 ARG B528-66.668-25.472-30.3851.0026.33N

Atom 16344 NH2 ARG B528-68.424-26.920-30.6151.0025.49N

Atom 16347C ARG B528-70.225-19.415-27.0041.0030.42C

Atom 16348O ARG B528-70.721-19.582-25.8851.0030.30O

Atom 16350N VAL B529-69.455-18.376-27.3071.0029.96N

Atom 16351 CA VAL B529-69.194-17.312-26.3421.0029.47C

Atom 16353 CB VAL B529-68.261-16.227-26.9321.0029.40C

Atom 16355 CG1 VAL B529-68.269-14.968-26.0811.0029.18C

Atom 16359 CG2 VAL B529-66.845-16.782-27.0621.0028.90C

Atom 16363C VAL B529-70.516-16.723-25.8411.0028.98C

Atom 16364O VAL B529-70.759-16.682-24.6411.0028.97O

Atom 16366N LEU B530-71.384-16.308-26.7521.0028.54N

Atom 16367 CA LEU B530-72.709-15.824-26.3531.0028.23C

Atoms 16369 CB LEU B530-73.631-15.604-27.5591.0028.09C

Atom 16372 CG LEU B530-73.767-14.150-28.0071.0028.15C

Atom 16374 CD1 LEU B530-72.412-13.570-28.4061.0027.99C

Atom 16378 CD2 LEU B530-74.784-14.034-29.1501.0028.85C

Atom 16382C LEU B530-73.389-16.767-25.3671.0027.88C

Atom 16383O LEU B530-73.932-16.319-24.3631.0028.11O

Atom 16385N SER B531-73.352-18.066-25.6521.0027.28N

Atom 16386 CA SER B531-74.081-19.049-24.8491.0026.68C

Atom 16388 CB SER B531-74.209-20.363-25.6121.0026.68C

Atom 16391 OG SER B531-72.970-21.033-25.6811.0026.67O

Atom 16393C SER B531-73.410-19.312-23.5141.0026.20C

Atom 16394O SER B531-74.076-19.550-22.5111.0025.86O

Atom 16396N VAL B532-72.085-19.281-23.5121.0025.86N

Atom 16397 CA VAL B532-71.320-19.562-22.3061.0025.51C

Atom 16399 CB VAL B532-69.891-20.055-22.6511.0025.34C

Atom 16401 CG1 VAL B532-68.955-19.932-21.4601.0024.01C

Atom 16405 CG2 VAL B532-69.950-21.484-23.1581.0024.95C

Atom 16409C VAL B532-71.271-18.357-21.3731.0025.52C

Atom 16410O VAL B532-71.377-18.523-20.1641.0025.82O

Atom 16412N ILE B533-71.137-17.158-21.9351.0025.39N

Atom 16413 CA ILE B533-70.875-15.954-21.1511.0025.48C

Atom 16415 CB ILE B533-69.666-15.185-21.7321.0025.30C

Atom 16417 CG1 ILE B533-68.375-15.928-21.4511.0024.91C

Atom 16420 CD1 ILE B533-68.118-16.120-19.9891.0025.00C

Atom 16424 CG2 ILE B533-69.553-13.797-21.1301.0025.81C

Atom 16428C ILE B533-72.065-14.983-21.0301.0025.77C

Atom 16429O ILE B533-72.537-14.707-19.9281.0025.77O

Atom 16431N THR B534-72.541-14.442-22.1421.0025.98N

Atom 16432 CA THR B534-73.446-13.295-22.0641.0026.31C

Atom 16434 CB THR B534-73.094-12.253-23.1431.0026.21C

Atom 16436 OG1 THR B534-72.914-12.909-24.3971.0026.72O

Atom 16438 CG2 THR B534-71.795-11.535-22.7811.0025.97C

Atom 16442C THR B534-74.961-13.621-22.0641.0026.50C

Atom 16443O THR B534-75.713-12.974-21.3441.0026.67O

Atoms 16445N GLU B535-75.410-14.616-22.8291.0026.55N

Atom 16446 CA GLU B535-76.851-14.892-22.9611.0026.50C

Atom 16448 CB GLU B535-77.197-15.197-24.4261.0026.68C

Atom 16451 CG GLU B535-77.226-13.936-25.2961.0027.68C

Atom 16454 CD GLU B535-78.193-14.014-26.4751.0028.75C

Atom 16455 OE1 GLU B535-79.370-13.588-26.3301.0027.72O

Atom 16456 OE2 GLU B535-77.762-14.492-27.5491.0030.06O

Atom 16457C GLU B535-77.355-16.019-22.0561.0026.19C

Atom 16458O GLU B535-77.021-17.171-22.2791.0026.15O

Atoms 16460N PRO B536-78.186-15.697-21.0471.0026.05N

Atom 16461 CA PRO B536-78.692-16.763-20.1961.0026.05C

Atom 16463 CB PRO B536-79.495-16.018-19.1181.0025.87C

Atom 16466 CG PRO B536-79.140-14.621-19.2391.0025.88C

Atom 16469 CD PRO B536-78.760-14.402-20.6601.0026.21C

Atom 16472C PRO B536-79.608-17.717-20.9431.0026.14C

Atom 16473O PRO B536-80.173-17.359-21.9731.0025.99O

Atom 16474N ILE B537-79.746-18.924-20.4111.0026.38N

Atom 16475 CA ILE B537-80.662-19.905-20.9601.0026.58C

Atom 16477 CB ILE B537-80.443-21.292-20.3331.0026.47C

Atom 16479 CG1 ILE B537-79.023-21.789-20.6001.0026.38C

Atom 16482 CD1 ILE B537-78.709-23.102-19.9071.0026.40C

Atom 16486 CG2 ILE B537-81.430-22.300-20.8901.0026.71C

Atom 16490C ILE B537-82.072-19.420-20.6571.0026.93C

Atom 16491O ILE B537-82.347-18.965-19.5451.0026.81O

Atom 16493N LEU B538-82.963-19.491-21.6411.0027.36N

Atom 16494 CA LEU B538-84.309-18.984-21.4391.0027.68C

Atom 16496 CB LEU B538-85.181-19.094-22.6981.0027.75C

Atom 16499 CG LEU B538-84.782-18.291-23.9491.0027.47C

Atom 16501 CD1 LEU B538-85.992-18.109-24.8441.0027.11C

Atom 16505 CD2 LEU B538-84.164-16.933-23.6211.0026.99C

Atom 16509C LEU B538-84.919-19.752-20.2881.0028.01C

Atom 16512N PRO B539-85.645-19.046-19.4211.0028.69N

Atom 16513 CA PRO B539-86.028-19.631-18.1521.0029.05C

Atom 16515 CB PRO B539-86.640-18.452-17.3971.0029.08C

Atom 16518 CG PRO B539-87.144-17.548-18.4471.0028.86C

Atom 16521 CD PRO B539-86.298-17.748-19.6601.0028.62C

Atom 16524C PRO B539-87.035-20.767-18.2591.0029.51C

Atom 16525O PRO B539-87.665-20.970-19.2971.0029.23O

Atoms 16526N PHE B540-87.164-21.500-17.1591.0030.25N

Atom 16527 CA PHE B540-88.089-22.613-17.0701.0030.56C

Atom 16529 CB PHE B540-87.971-23.297-15.7081.0030.73C

Atom 16532 CG PHE B540-88.848-24.499-15.5671.0030.49C

Atom 16533 CD1 PHE B540-89.910-24.505-14.6831.0030.32C

Atom 16535 CE1 PHE B540-90.718-25.614-14.5681.0030.59C

Atom 16537 CZ PHE B540-90.475-26.722-15.3461.0030.55C

Atom 16539 CE2 PHE B540-89.420-26.720-16.2341.0030.68C

Atom 16541 CD2 PHE B540-88.619-25.617-16.3421.0030.43C

Atom 16543C PHE B540-89.507-22.120-17.2571.0030.76C

Atom 16544O PHE B540-89.967-21.257-16.5081.0030.59O

Atom 16546N GLU B541-90.184-22.677-18.2591.0031.13N

Atom 16547 CA GLU B541-91.553-22.289-18.6081.0031.45C

Atom 16549 CB GLU B541-91.525-21.186-19.6801.0031.60C

Atom 16552 CG GLU B541-92.860-20.454-19.9111.0032.56C

Atom 16555 CD GLU B541-93.773-21.133-20.9351.0033.64C

Atom 16556 OE1 GLU B541-93.261-21.922-21.7711.0035.06O

Atom 16557 OE2 GLU B541-95.002-20.868-20.9011.0032.44O

Atoms 16558C GLU B541-92.326-23.510-19.1051.0031.31C

Atom 16559O GLU B541-92.860-24.286-18.3101.0031.30O

Atom 16562 MG MG C1-42.84411.42713.3091.0046.29 MG

Atom 16561 MG MG C2-46.615-18.454-33.2311.0048.45 MG

Atom 16563O HOH E1-50.507-5.408-4.4911.0017.42O

Atom 16566O HOH E2-64.748-36.007-11.7251.002.00O

Atom 16569O HOH E3-40.643-2.220-34.9961.002.00O

Atom 16572O HOH E4-36.090-9.757-37.0741.0017.20O

Atom 16575O HOH E5-46.117-37.662-22.9161.0017.03O

Atom 16578O HOH E6-49.54135.4766.9211.0014.03O

Atom 16581O HOH E7-32.28827.57216.4431.0013.16O

Atom 16584O HOH E8-50.70610.207-15.0611.0018.73O

Atom 16587O HOH E9-77.18836.767-9.2181.008.05O

Atom 16590O HOH E10-90.260-31.248-21.0711.002.00O

Atom 16593O HOH E11-70.920-33.414-3.8841.009.35O

Atom 16596O HOH E12-37.761-21.294-9.2491.0025.78O

Atom 16599O HOH E13-76.05023.855-18.2931.002.00O

Atom 16602O HOH E14-76.876-19.575-22.8561.0019.25O

Atom 16605O HOH E15-40.93611.629-24.8321.0022.29O

Atom 16608O HOH E16-85.55134.8323.2601.0025.14O

Atom 16611O HOH E17-56.82531.771-7.4641.0017.27O

Atom 16614O HOH E18-76.22239.261-. 6131.0025.47O

Various modifications and variations of the described methods and systems of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. While the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in the relevant fields are intended to be within the scope of the following claims.

Claims

1. An isolated poplar isoprene synthase variant, wherein said variant comprises a truncation in the amino-terminal portion of isoprene synthase.

2. The isolated poplar isoprene synthase variant of claim 1, wherein the isoprene synthase variant has increased specific activity compared to a full-length isoprene synthase.

3. The isolated poplar isoprene synthase variant of claim 1, wherein the isoprene synthase is SEQ ID NO: poplar (p. alba) isoprene synthase from 120.

4. The isolated poplar isoprene synthase variant of claim 3, wherein the variant is selected from the group consisting of an MEA variant (SEQ ID NO: 122), an MSV variant (SEQ ID NO: 124), an MVS variant (SEQ ID NO: 126), an MTE variant (SEQ ID NO: 128), an MNV variant (SEQ ID NO: 130).

5. The isolated poplar isoprene synthase variant of claim 4, wherein said variant is an MEA variant (SEQ ID NO: 122).

6. The isolated poplar isoprene synthase variant of claim 3, wherein the variant is selected from the group consisting of a TRC (-3) variant (SEQ ID NO: 136), a TRC (-4) variant (SEQ ID NO: 138), a TRC (-5) variant (SEQ ID NO: 140), a TRC (-6) variant (SEQ ID NO: 142), and a TRC (-7) variant (SEQ ID NO: 144).

7. The isolated poplar isoprene synthase variant of claim 1, wherein the variant is a MET variant of populus tremuloides isoprene synthase (SEQ ID NO: 146).

8. The isolated poplar isoprene synthase variant of claim 1, wherein the variant is a MET variant of Populus pilosus isoprene synthase (SEQ ID NO: 148).

9. An isolated poplar isoprene synthase variant, wherein the variant comprises a substitution of one or more amino acid residues of a wild-type isoprene synthase; and wherein the isoprene synthase variant has increased isoprene synthase activity as compared to a wild-type isoprene synthase.

10. The isolated poplar isoprene synthase variant of claim 9, wherein increased isoprene synthase activity is indicated by a host cell comprising the isoprene synthase variant growing at a faster rate in the presence of dimethylallyl pyrophosphate (DMAPP) compared to a host cell comprising a parent isoprene synthase.

11. The isolated poplar isoprene synthase variant of claim 9, wherein the isoprene synthase is SEQ ID NO: poplar isoprene synthase of 120.

12. The isolated poplar isoprene synthase variant according to claim 11, wherein the variant comprises one of the amino acid substitutions selected from the group consisting of V10M, F12S, T15A, E18G, V58I, V58F, L70Q, L70V, T71V, V79V, E89V, G94V, S119V, F120V, G127V, E175V, T212V, S257V, R36262, a 266V, F280V, N297V, F305V, L319V, E323V, a 328V, D V, a 359V, K366V, E368V, L374V, S396V, V418V, K V, H440V, T442, T V, I449V, a 4672, K V, S396V, N507V, N36.

13. The isolated poplar isoprene synthase variant of claim 11, wherein at least one amino acid substitution is an L70R substitution.

14. The isolated poplar isoprene synthase variant according to claim 11, wherein said variant comprises one of the amino acid substitutions selected from the group consisting of G127R/F511Y, L70Q/G94A/R262G/F305L, F12S/T15A/E18G/N297K, S396T/T442I, V10M/E323K, F120L/a266G, K438N/K500R, V79L/S509N, E175V/S257A/E368D/a46 469S, T71S/L374S, F280S/H440S, E89S/H440S, V58S/a 328S/N532S, S36119/D36342/I449S, and K S/G36366.

15. Comprises the amino acid sequence of SEQ ID NO: 120 (figure 19).

16. A method of producing isoprene, comprising: (a) providing a host cell comprising an expression vector comprising a polynucleotide sequence encoding an isoprene synthase variant; and (b) culturing the host cell under conditions suitable for the production of isoprene.

17. The method of claim 16, further comprising (c) recovering the isoprene.

18. The method of claim 17, further comprising (d) polymerizing the isoprene.

19. A method for detecting isoprene synthase activity, comprising: (a) culturing a host cell comprising an expression vector under conditions suitable for production of the isoprene synthase variant; (b) lysing the host cells with a lysis buffer comprising lysozyme to produce a cell lysate; and (c) detecting isoprene synthase activity in the cell lysate by measuring isoprene production from dimethylallyl Diphosphate (DMAPP).

20. The method of claim 19, wherein the host cell is selected from the group consisting of a gram-positive bacterial cell, a gram-negative bacterial cell, a filamentous fungal cell, and a yeast cell.

21. The method of claim 19, wherein the host cell is selected from the group consisting of Escherichia species (Escherichia sp.) (Escherichia coli), pantoea species (pantoa sp.) (pantoea citrea), Bacillus species (Bacillus sp.) (Bacillus subtilis), Yarrowia species (Yarrowia sp.) (Yarrowia lipolytica), and Trichoderma (Trichoderma reesei).

22. The method of claim 19, wherein the host cell is cultured in a medium comprising a carbon source selected from the group consisting of glucose, glycerol, dihydroxyacetone, yeast extract, biomass, molasses, sucrose and oil.

23. A method for detecting isoprene in multiple samples with a high throughput screen, comprising:

(a) providing: i) a plurality of samples each comprising isoprene synthase; ii) a glass plate comprising a plurality of wells; and iii) a cover for the glass plate;

(b) placing multiple samples in multiple wells of a glass plate;

(c) sealing the glass plate with a cover to produce a sealed glass plate having a headspace associated with the sample in each of the plurality of wells;

(d) Incubating the glass plate under conditions in which isoprene synthase is active;

(e) isoprene in the headspace was detected.

24. The method of claim 23, wherein the isoprene is detected by gas chromatography-mass spectrometry (GC-MS).

25. The method of claim 23, wherein the plurality of samples comprises host cells comprising an expression vector comprising a polynucleotide sequence encoding an isoprene synthase variant operably linked to a promoter.

26. The method of claim 23, wherein the multiple samples comprise a lysate of host cells, lysozyme, and dimethylallyl Diphosphate (DMAPP).

27. The method of claim 23, wherein said glass sheet is a deep hole glass block.

28. The method of claim 23, wherein the plurality of wells comprises at least 24 wells.

29. The method of claim 23, wherein the plurality of wells each comprise a volume of 2ml or less.

30. A host cell comprising a heterologous polynucleotide sequence encoding an isoprene synthase variant operably linked to a promoter, wherein the isoprene synthase variant comprises a substitution at a position corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues of poplar isoprene synthase.

31. The host cell of claim 30, wherein the isoprene synthase is SEQ ID NO: poplar isoprene synthase of 120.

32. The host cell of claim 31, wherein the variant is selected from the group consisting of MEA variant (SEQ ID NO: 122), MSV variant (SEQ ID NO: 124), MVS variant (SEQ ID NO: 126), MTE variant (SEQ ID NO: 128), MNV variant (SEQ ID NO: 130).

33. The host cell of claim 31, wherein the variant is selected from the group consisting of a TRC (-3) variant (SEQ ID NO: 136), a TRC (-4) variant (SEQ ID NO: 138), a TRC (-5) variant (SEQ ID NO: 140), a TRC (-6) variant (SEQ ID NO: 142), and a TRC (-7) variant (SEQ ID NO: 144).

34. The host cell of claim 30, wherein the variant is a MET variant of Populus tremuloides isoprene synthase (SEQ ID NO: 146).

35. The host cell of claim 30, wherein said variant is a MET variant of Populus pilosus isoprene synthase (SEQ ID NO: 148).

36. A host cell according to claim 31, wherein the variant comprises one of the amino acid substitutions selected from the group consisting of V10M, F12S, T15A, E18G, V58I, V58F, L70Q, L70V, T71V, V79V, E89V, G94V, S119V, F120V, G127V, E175V, T212V, S257V, R262V, a 266V, F280V, N297V, F305V, L319V, E323V, a 328V, D342V, a 359V, K V, E368V, L374V, S396V, V418V, K438V, H440V, T396 36442, I4636442, a 463672, K36509, K V, N396V, N507V, N319V, N.

37. The host cell of claim 36, wherein at least one amino acid substitution is an L70R substitution.

38. A host cell according to claim 31, wherein the variant comprises one of a plurality of amino acid substitutions selected from the group consisting of G127R/F511Y, L70Q/G94A/R262G/F305L, F12S/T15A/E18G/N297K, S396T/T442I, V10M/E323K, F120L/a266G, K438N/K500R, V79L/S509N, E175V/S257A/E368D/a469S, T71S/L374S, F280S/H440S, E89S/H440S, V58S/a 328S/N532S, S119S/D S/I449S and K S/G507.

39. The host cell of claim 30, wherein the polynucleotide sequence is contained within a plasmid.

40. The host cell of claim 39, wherein the polynucleotide sequence is integrated into the chromosome of the host cell.

41. The host cell of claim 30, wherein the host is selected from the group consisting of a gram-positive bacterial cell, a gram-negative bacterial cell, a filamentous fungal cell, and a yeast cell.

42. The host cell of claim 30, wherein said host is selected from the group consisting of escherichia species (e.coli), pantoea species (e.g., pantoea citrea), bacillus species (e.subtilis), yarrowia species (e.g., yarrowia lipolytica), and trichoderma (e.g., trichoderma reesei).

43. The host cell of claim 30, wherein the host is cultured in a medium comprising a carbon source selected from the group consisting of glucose, glycerol, dihydroxyacetone, yeast extract, biomass, molasses, sucrose and oil.

44. The host cell of claim 30, wherein the host cell further comprises a heterologous or native nucleic acid encoding an IDI polypeptide and/or a heterologous or native nucleic acid encoding a DXS polypeptide, optionally in combination with a native DXP pathway.

45. The host cell of claim 30, wherein the host cell further comprises one or more nucleic acids encoding an IDI polypeptide and a DXS polypeptide.

46. The host cell of claim 30, wherein the host cell comprises one vector encoding the isoprene synthase variant, the IDI polypeptide, and the DXS polypeptide.

47. The host cell of claim 46, wherein the host cell further comprises a heterologous nucleic acid encoding a MVA pathway polypeptide selected from the group consisting of MVA pathway polypeptides from Saccharomyces cerevisiae (Saccharomyces cerevisiae) and Enterococcus faecalis (Enterococcus faecalis).

48. The host cell of claim 30, wherein the host cell further comprises one or more nucleic acids encoding a MVA pathway polypeptide and a DXS polypeptide and wherein one vector encodes the isoprene synthase variant, MVA pathway polypeptide, and DXS polypeptide.

49. The host cell of claim 48, wherein the host cell further comprises one or more nucleic acids encoding a DXS polypeptide, an IDI polypeptide, or one or more of the remaining DXP pathway polypeptides and a MVA pathway polypeptide.

50. A method of producing isoprene, comprising:

(a) culturing the host cell of claim 30 under suitable culture conditions for the production of isoprene; and

(b) producing isoprene.

51. The method of claim 50, further comprising (c) recovering the isoprene.

52. The method of claim 51, further comprising (d) polymerizing isoprene.

53. A method of producing isoprene synthase, comprising:

(a) providing: (i) a host cell; and (ii) a nucleic acid encoding an isoprene synthase variant operably linked to a promoter, wherein the isoprene synthase variant is mutated in a region that is complementary to a region of SEQ ID NO: 120 at positions corresponding to one or more (1, 2, 3, 4, 5, 6, 7, 8, 9, or 10) residues;

(b) contacting a host cell with the nucleic acid to produce a transformed host cell; and

(c) the transformed host cells are cultured under suitable culture conditions for the production of isoprene synthase.