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WO2009115664A2 - Structure cristalline du domaine cc2-lz de nemo - Google Patents

Structure cristalline du domaine cc2-lz de nemo Download PDF

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WO2009115664A2
WO2009115664A2 PCT/FR2009/000127 FR2009000127W WO2009115664A2 WO 2009115664 A2 WO2009115664 A2 WO 2009115664A2 FR 2009000127 W FR2009000127 W FR 2009000127W WO 2009115664 A2 WO2009115664 A2 WO 2009115664A2
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atom
leu
glu
lys
gln
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WO2009115664A3 (fr
Inventor
Fabrice Agou
Jeanne Chiaravalli
Stéphane DUQUERROY
Elisabeth Fontan
Olivera Grubisha
Monika Dorota Kaminska
Michel Veron
Florence Cordier
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Laboratoires Servier SAS
Institut Pasteur
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Laboratoires Servier SAS
Institut Pasteur
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Priority to EP09722579A priority Critical patent/EP2240513A2/fr
Priority to CA2713884A priority patent/CA2713884A1/fr
Priority to JP2010545522A priority patent/JP5529759B2/ja
Priority to EA201001228A priority patent/EA020189B1/ru
Priority to AU2009227090A priority patent/AU2009227090B2/en
Priority to US12/735,671 priority patent/US8440790B2/en
Publication of WO2009115664A2 publication Critical patent/WO2009115664A2/fr
Publication of WO2009115664A3 publication Critical patent/WO2009115664A3/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B15/00—ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
    • G16B15/30—Drug targeting using structural data; Docking or binding prediction
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B15/00—ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment

Definitions

  • the subject of the present invention is a crystal of the NEMO CC2-LZ domain of sufficient size and quality to make it possible to obtain structural data by X-ray diffraction crystallography.
  • the invention relates to the use of NEMO's crystallographic data and three-dimensional structure of the CC2-LZ domain to identify, model, and design compounds that modulate the NF-ÎoB signaling pathway.
  • the NF-kB pathway is activated in response to various extracellular stimuli such as bacterial LPS, proinflammmatoires of cytokines such as IL 1 I 1 and TNF (MS Hayden and S. Ghosh, Signaling to NF-kappaB, Genes Dev 18 (2004 ), no.18, 2195-2224). Signals are typically transmitted from cell receptors to the IKK complex, a pivotal regulator of the signaling pathway.
  • the IKK complex is composed of two kinases IKK ⁇ and IKK ⁇ and a regulatory protein NEMO (NF- ⁇ B essential modulator) (S. Yamaoka et al., Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation, CeII 93 (1998), No. 7, 1231-1240).
  • NEMO plays a crucial role in integrating signals from various stimuli and inducing activation of the IKK complex.
  • the NEMO protein is constituted in its N-terminal portion of a binding domain to the IKK complex and in its C-terminal portion of an oligomerization domain (FIG. 1). Note that murine NEMO proteins (SEQ ID NO. 1)
  • Activation of the IKK complex proceeds through a mechanism related to the ability of the NEMO protein to oligomerize by trans-activation via an IKKK kinase or by trans-autoactivation via dimerization of IKKs kinases.
  • the mechanism of activation of the IKK complex via NEMO is not fully elucidated, although many reports show that oligomerization and attachment to K-63 polyubiquitins involving NEMO's minimal domain CC2-LZ play a pivotal role (JL Poyet et al., Activation of the IkappaB kinases by RIP via Ikkgamma / NEMO-mediated oligomerization, J
  • the minimal domain of CC2-LZ oligomerization of NEMO (aa 251-337 in mice, aa 258-344 in humans) is composed of two successive motifs, a coiled-coil CC2 motif (aa 251-290 in mice , aa 258-297 in humans) and a LZ leucine zipper motif (aa 293-337 in mice, aa 300-344 in humans). Variations of one to two amino acids at the ends of the CC2-LZ domain can be observed depending on the software used for the prediction of CC2 and LZ structures.
  • the IKK complex phosphorylates IKB proteins, triggering the degradation of these proteins by the 26S proteasome and then releasing the NF-ÎoB transcription factors that are sequestered in the cytoplasm by the IKB proteins.
  • the NF-ÎoB transcription factor then migrates into the nucleus and regulates the expression of genes involved in inflammation, immunity, apoptosis and cell survival. Constitutive activation of the NF-ÎoB pathway is involved in oncogenesis.
  • the IKK complex has emerged as a very attractive target for the development of anti-inflammatory and anti-tumor compounds (MA Calzado et al., NF-kappaB inhibitors for the treatment of inflammatory diseases and cancer, Curr Med Chem 14 (2007). 3, 367-376) (TD Gilmore and M. Herscovitch, Inhibitors of NF-kappaB signaling: 785 and counting, Oncogene 25 (2006), no.51, 6887-6899) (F. D'Acquisto et al. al., Inhibition of nuclear factor kappa
  • NF-kB An emerging theme in anti-inflammatory therapies, Mol Interv 2 (2002), No. 1, 22-35.
  • the design of NEMO-targeting compounds rather than kinases selectively suppresses stimuli-dependent IKK activity and thereby decreases the cytotoxicity of such compounds.
  • the NEMO protein and the CC2-LZ domain in particular have thus far been unsuccessful.
  • the purpose of the present invention is therefore to propose a new strategy for obtaining the crystallization of the CC2-LZ domain of the NEMO protein.
  • This alternative strategy is based on an increase in the rigidity of the minimal oligomerization domain of NEMO.
  • the crystalline structure was resolved by X-ray diffraction crystallography with a resolution of 3.25 ⁇ .
  • the crystalline structure was resolved by X-ray diffraction crystallography with a resolution of 2.9 ⁇ .
  • the present invention also relates to crystallization methods of the CC2-LZ domain.
  • the CC2-LZ crystals and the information derived therefrom can be analyzed for the purpose of identifying or designing compounds that interact with CC2-LZ.
  • the present invention thus relates to a crystal of the mammalian NEMO CC2-LZ domain whose peptide domain CC2-LZ has the amino acid sequence SEQ ID NO.3 and whose peptide variants are derived from said amino acid sequence.
  • crystal In the context of the invention the terms “crystal”, “crystal of the CC2-LZ domain”, “crystal of a CC2-LZ complex” and “co-crystal of the CC2-LZ domain” are used indistinctly and refer to a crystal of a complex comprising at least two distinct entities.
  • An entity of the crystal according to the invention is the CC2-LZ domain or one of its variants.
  • the present invention also relates to a crystal of a mammalian NEMO CC2-LZ domain complex whose peptide domain CC2-LZ has the amino acid sequence SEQ ID NO.4 and whose peptide variants are derived from said amino acid sequence.
  • amino acid sequence is to be understood a peptide sequence isolated from the natural context. These include isolated sequences, synthesized chemically and / or purified and possibly modified by genetic engineering.
  • variants are meant the amino acid sequences of the peptides described above comprising conservative substitutions or conservative point mutations and having essentially the same properties as the peptides, respectively, encoded by the sequences SEQ ID NO. 3 and SEQ ID NO. .4, the ability to oligomerize and bind to K-63 polyubiquitins.
  • Mesh parameter denotes the parameters a, b and c of the crystalline mesh corresponding to the lengths of the basic non-coplanar vectors (a, b, c), and the angles ⁇ , ⁇ and ⁇ which are formed between the vectors ( a, b, c).
  • the angle ⁇ is the angle between the vectors b and c, the angle ⁇ between the vectors a and c, and ⁇ that between the vectors a and c.
  • crystal mesh is meant the parallelepiped constructed by the vectors (a, b, c).
  • the crystal of a CC2-LZ domain complex according to the present invention is not limited to the native CC2-LZ domain. Indeed, the crystal of a complex according to the invention comprises mutants of native CC2-LZ. These mutants are obtained by addition, deletion or substitution of at least one amino acid in the native CC2-LZ polypeptide sequence and have substantially the same three-dimensional structure as that of the native CC2-LZ domain.
  • having substantially the same three-dimensional structure it is meant having a set of atomic structure coordinates from a crystal having a mean deviation of less than or equal to 5 A, preferably 2 A, when superimposes on the atomic structure coordinates of native CC2-LZ from which the mutant is derived when at least 50% to about 100% of the native CC2-LZ alpha carbon atoms are included in the superposition.
  • the invention preferably relates to a co-crystal, comprising the domain
  • ankyrin modular proteins of varying sizes involved in multiple protein: protein interactions.
  • Ankyrins are genetically conserved proteins found in bacteria, plants, fungi and animals and whose structure is based on repeating structural units of about 33 amino acids.
  • An "ankyrin fragment” according to the invention is capable of binding and stabilizing the complex formed with the NEMO CC2-LZ domain.
  • the invention relates to a crystal of the CC2-LZ domain of a mammalian NEMO protein and an ankyrin 1 D5 (SEQ ID NO.5).
  • the invention also provides a crystal of the CC2-LZ domain of a mammalian NEMO protein and a 2A1 or 2F6 ankyrin as described by Wyler et al. (Inhibition of NF-kappaB activation with ankyrin-repeat targeting proteins targeting the ubiquitin-binding / oligomerization domain of NEMO, Protein Sci 16 (2007), No. 9, 2013-2022).
  • the CC2-LZ domain is complexed with ankyrin 1 D5, which binds to CC2-LZ with high affinity and stiffens the peptide domain.
  • LZ complexed with ankyrin 1 D5 is used to determine the three-dimensional structure of CC2-LZ by molecular replacement.
  • the ankyrin or the ankyrin fragment is complexed to the LZ motif of the CC2-LZ domain in order, more specifically, to stabilize it.
  • the LZ pattern is more flexible and thermodynamically more unstable than the CC2 pattern of the CC2-LZ domain.
  • the co-crystal of the NEMO CC2-LZ domain with ankyrin protein can be obtained by a crystallization process comprising the following steps:
  • the CC2-LZ crystallization process corresponds to the process as described in Example 1.
  • the invention relates to the crystal of a NEMO CC2-LZ domain complex or the CC2-LZ co-crystal having the crystallographic coordinates described in Table 1.
  • the crystal and the co-crystal of the CC2-LZ domain according to the invention are respectively defined by their three-dimensional structure obtained by X-ray diffraction which is represented in FIGS. 2 and 3.
  • the three-dimensional structure of CC2-LZ forms an elongated dimer composed of two parallel ⁇ -helices that associate with each other to form a coiled-coil structure (Figure 2) ( Figure 3).
  • the dimer of CC2-LZ interacts with two molecules of ankyrin 1 D5, each ankyrin forming contacts with ⁇ helices on both LZ chains.
  • Three residues located between the CC2 motif and the LZ motif (aa 291-293, mouse numbering) form a pseudo coiled-coil.
  • the polyubiquitin chain binding domain K-63 which is described in Ea et al., Is composed of 67 amino acids (259-325 human numbering, 252- 318 numbering mice) corresponding to the C-terminal region of CC2 and the N-terminal region of LZ. Cross-referencing of data from three-dimensional structure, site-directed mutagenesis and sequence alignment
  • the region forming the ubiquitin binding site was determined between amino acids 293 and 323 in the murine polypeptide sequence of NEMO (aa 300-330 human numbering).
  • the three-dimensional structure of the CC2-LZ crystal and co-crystal according to the invention is obtained by a process comprising the following steps:
  • the method for determining the three-dimensional structure of CC2-LZ corresponds to the method as described in Example 1.
  • the invention also extends, on the one hand, to the murine CC2-LZ protein crystal comprising the Ala316Pro mutation (A316P) and / or the Phe305Ala mutation (F305A), and on the other hand to the crystal of the human protein of CC2-LZ also comprising the Ala323Pro mutation (A323P) and / or the Phe312Ala mutation (F312A).
  • the different mutations obtained by site-directed mutagenesis in the human CC2-LZ protein are shown in Figure 4.
  • the Glu296Ala mutation (E296A, position 289 in mice) is localized at the C-terminal end of CC2 and is outside the site of ubiquitin interaction (position aa 259-325, human numbering and aa 252-318, mouse numbering).
  • the mutations Phe312Ala (F312A, position 305 in mice) and Glu315Ala (E315A, position 308 in mice) are located in the ubiquitin binding site.
  • the mutations Glu315Ala and Ala323Pro are respectively involved in two human pathologies, the anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (R. Doffinger et al., Genetic heterogeneity of mendelian susceptibility to mycobacterial infection, Microbes Infect 2 (2000), No. 13, 1553-1557) and Incontinentia pigmenti (IP) (A. Smahi et al., Genomic rearrangement in nemo odd NF-kappaB activation and is a cause of incontinentia pigmenti. incontinentia pigmenti (IP) consortium,
  • EDA-ID anhydrotic ectodermal dysplasia with immunodeficiency
  • IP Incontinentia pigmenti
  • Leu329Ala Leu336Ala double mutation (L329A L336A, positions 322 and 329 respectively in the mouse) is located in the leucine zipper domain of CC2-LZ.
  • NEMO-deficient mouse embryonic fibroblasts are transiently co-transfected with the plasmid encoding the Ig ⁇ -luciferase reporter gene and with the plasmids encoding the different proteins and then stimulated by TNF ⁇ for 24 hours.
  • MEFs mouse embryonic fibroblasts
  • the mutations A323P and F312A generate the two strongest inhibitions, respectively 95% and 78% inhibition.
  • A323P mutation that causes a severe form of incontinentia pigmenti a lack of NEMO dimerization is responsible for the inactivation of the NF- ⁇ B pathway, a result similar to that obtained by Sebban- Benin et al. (Identification of TRAF ⁇ -dependent NEMO polyubiquitination sites through the analysis of a new NEMO mutant pathway incontinentia pigmenti, Hum Mo! Genet 16 (2007), No.23, 2805-2815).
  • the NEMO CC2-LZ domain protein mutated at position F312A shows an elution profile, in gel filtration, identical to that of the wild-type CC2-LZ protein, indicating that this mutation does not affect the stability of the dimer but modifies activation of the NF- ⁇ B pathway ( Figure 5).
  • the study of this mutant demonstrates for the first time that the lack of activation is not due to a lack of dimerization of the ubiquitin interaction site but to a lack of interaction with the K63 polyubiquitin chains as shown by Ea et al. Therefore, these results highlight the possibility of inhibiting the NF- ⁇ B pathway by either altering the NEMO dimerization or by inhibiting the interaction of NEMO with the polyubiquitin chains.
  • the present invention allows on the one hand the structural validation by directed mutagenesis of an active conformation of NEMO and on the other hand the determination of residues critical for the oligomerization of the protein and consequently for the activation of the IKK complex. as well as those involved in binding to K-63 polyubiquitins.
  • the invention relates preferably to a method of identifying compounds capable of binding to the NEMO CC2-LZ domain based on crystallographic data obtained in said invention. Peptides mimicking the sequence of CC2 or LZ are shown to be disruptive oligomerization of NEMO and thus suppress activation of the NF-ÎoB pathway in cells in culture.
  • the invention relates to the development and identification of compounds interfering with the oligomerization of the CC2-LZ domain, which inhibits the binding of said domain to polyubiquitins K-63.
  • the term "compounds” means any chemical molecule inhibiting the dimerization of the CC2-LZ domain of NEMO or inhibiting the interaction of the NEMO CC2-LZ domain with polyubiquitin chains.
  • the crystallographic data of the NEMO domain thus made it possible to design high affinity peptides for this protein.
  • the peptide probes according to the invention are preferably the peptide PH4 and the peptide P8RD having the respective amino acid sequences SEQ ID NO.6 and SEQ ID NO.7.
  • P8RD has an affinity of 60 nM whereas the peptide PH4 has an affinity of 170 nM.
  • These measurements are carried out at pH 7 and at ambient temperature in a stringent buffer corresponding to 20 mM Tris-Acetate-MES containing 200 mM potassium chloride and 0.5% Tween 20. They are carried out by fluorescence polarization using N-terminal coupled peptides with Fluorescein or Cy5 fluorophores.
  • the peptides can be coupled to all kinds of fluorophores.
  • the present invention finally relates to a method for identifying compounds of NEMO dimerization or the interaction of NEMO with polyubiquitin chains between a peptide probe according to the invention and the NEMO CC2-LZ domain.
  • This method of high throughput screening or HTS (High Throughput Screening) screening comprises the following steps:
  • complex model is meant the three-dimensional structure of the CC2-LZ / ubiquitin complex.
  • the NEMO / ubiquitin CC2-LZ complex model was constructed based on the structural information obtained from the ILJIM-Rabbit-5 / ubiquitin complex (Lee S. et al., Structural basis for ubiquitin recognition and autoubiquitination by Rabex-5 Nat Struct Mol Biol 13, 264-271, 2006).
  • the CC2-LZ / ubiquitin complex model has been experimentally verified through the chemical shifts observed by NMR of the interaction between ubiquitin and the NEMO CC2-LZ domain ( Figure 9).
  • the three-dimensional structure of the NEMO CC2-LZ domain is deduced from the CC2-LZ / ubiquitin complex model.
  • This three-dimensional structure of CC2-LZ can be used for in silico design or in silico screening of compounds capable of binding to the NEMO CC2-LZ domain.
  • the present invention thus relates to a method of designing compounds capable of binding to the NEMO CC2-LZ domain using the three-dimensional structure of the CC2-LZ domain obtained from the crystallographic coordinates of the crystal according to the invention.
  • the invention extends to compounds identified from the identification and design methods supra.
  • these compounds inhibit the dimerization of the NEMO CC2-LZ domain or inhibit the interaction of the NEMO CC2-LZ domain with the polyubiquitin chains.
  • Figure 1 Representation of the NEMO protein.
  • Figure 2 Three-dimensional structure of the NEMO CC2-LZ domain complexed with two molecules of ankyrins. The two subunits of the
  • CC2-LZ are dark gray whereas ankyrines are light gray.
  • Figure 3 Structure of the NEMO CC2-LZ domain in the complex with ankyrins 1 D5. Seen from the side of the complex in ribbons diagram. The NEMO propellers are represented in gray level according to the CC2, NOA or LZ domain. Ankyrin chains 1 D5 are dark gray in lateral position.
  • Figure 4 Localization in the human CC2-LZ domain of the different mutations obtained by site-directed mutagenesis.
  • the polyubiquitin binding domain is shown in white.
  • the numbering used for amino acids corresponds to that of the human protein.
  • Figure 5 Effect of the different mutations on the activation of the NF-KB pathway.
  • the numbering of the mutations corresponds to that of the human CC2-LZ protein.
  • Figure 6 Model of the NEMO / ubiquitin CC2-LZ Domain Complex. Sequence of alignment between Rabex-5 (MIU / IUIM) (first line) and NEMO (NOA pattern) (second line) with below the positions of NOA (ag) structural motif.
  • the vertical lines in solid and dashed lines designate identical and similar residues respectively.
  • the diagonal line indicates spatially similar residues in view of the structural model according to the invention.
  • the residues strictly conserved in the NOA motif are indicated by *.
  • Figure 7 Seen from the side of the NEMO CC2-LZ / ubiquitin complex. The helices of NEMO are colored as in FIG. 3.
  • the ubiquitin molecules are gray in lateral position and the 1D5 molecules of co-crystal ankyrins are in semi-transparent light gray also in lateral position.
  • Figure 8 Closely viewed from the NOA / ubiquitin interface. The residues involved in the interaction are drawn in a "lease and stick" representation with carbon atoms in gray (ubiquitin) and white (NEMO).
  • Figure 9 Chemical shifts observed by NMR of ubiquitin bound to the NEMO CC2-LZ domain. Mean variations of the chemical shift ⁇ av according to the chemical residue. The elements of the corresponding secondary structure are represented above the graph of chemical shifts.
  • Figure 10 Representation of the interaction between ubiquitin and the NOA region of the CC2-LZ domain.
  • ankyrin 1 D5 The evolution of ankyrin 1 D5 is performed by ribosome display using the N2C DARPin library (designed ankyrin repeat protein) (HK Binz et al., High affinity binders selected from ankyrin repeat protein libraries, Nat Biotechnol 22 (2004)). ), no.5, 575-582) for selection.
  • N2C DARPin library designed ankyrin repeat protein
  • the results of this study as well as the amino acids of ankyrin 1D5 which differ from the initial model are described in the publication of Wyler et al.
  • the cDNA of ankyrin 1 D5 is cloned into the pQE30 vector (Qiagen) in phase with a histidine tag located on the N-terminal side. Plasmid pQE30-1 D5 is introduced into a strain of E.
  • Fractions containing the protein are pooled and dialyzed against 20 mM Tris / HCl pH 7.6, 50 mM buffer. KCI using dialysis bags with a cutoff of 6-8 kDa (Spectra / Por). The protein is concentrated by ultrafiltration in Amicon tubes (Millipore) with a cut-off of 5 kDa.
  • the CC2-LZ domain (SEQ ID NO.3) (aa 251-337 of murine NEMO) is cloned into the plasmid pET28 in phase with a histidine tag located on the N-terminal side. This domain corresponds to residues 258-344 of human NEMO (SEQ ID NO.4).
  • the protein is expressed in a strain of E. coli, BL21-gold (DE3), and purified on a nickel column as described for purification of ankyrin 1 D5.
  • the CC2-LZ protein is then purified on a cation exchange column, Poros 20-HS (Perseptive Biosystem).
  • the column is pre-equilibrated in the buffer 50 mM MES pH 7.1, 50 mM KCl and the proteins are eluted by a linear gradient of KCl. Fractions of interest are pooled and dialyzed against a 20mM Tris / HCl buffer pH 8.0, 100mM KCl, then concentrated by ultrafiltration.
  • the purity of the protein is estimated to be greater than 98% by electrophoresis analysis under denaturing conditions and staining with Coomassie blue.
  • the protein concentration is determined by the Bradford method and by measurement of absorption at 280 nm using an absorption coefficient of 2312 M -1 cm -1 for CC 2 -LZ and 1490 M -1 cm -1 for the 1 D5.
  • Proteins 1 D5 and CC2-LZ are incubated together for 30 min in ice and the complex is purified on a Superdex 200 HR column (Pharmacia) equilibrated in 20 mM Tris / HCl buffer pH 8, 100 mM KCl.
  • the binding stoichiometry in the complex is 1: 1.
  • the complex is concentrated by ultrafiltration to obtain a protein concentration of 10-13 mg / ml.
  • the 3A4 tank solution contains: 10% PEG 40000, 5% isopropanol, 100 mM Na Hepes pH 7.5, and 8B5 solution contains: 5% MPD (2-methyl-2,4-pentadiol), 5% ethanol, 100 mM Na Hepes pH7.5.
  • the crystals grew under vapor diffusion in suspended droplets seeded with microcrystals (microseeding). 1 .mu.l of the protein complex is added to 1 .mu.l of the reservoir solution and equilibrated under vapor diffusion at 18-20 0 C for more than 36 hours. Micro crystals (0.1 ⁇ l) obtained from crystal fragments are introduced into the drop. After seeding, the crystals grow in a few days to reach a size of 300x150x20 ⁇ m. For cryogenic protection, the crystals are immersed for 30 seconds in the reservoir solution containing in addition to the
  • the crystals are mounted on nylon loops and frozen very quickly before data collection.
  • the best candidates for modeling the CC2-LZ / ubiquitin complex are structures comprising a simple ⁇ -helix such as I 1 UIM (ubiquitin-interacting motif) and I 1 inverted UIM (IUIM or MIU) derived from Rabex-5.
  • I 1 UIM ubiquitin-interacting motif
  • IUIM I 1 inverted UIM
  • the IUIM motif of Rabex-5 binds to the hydrophobic region of ubiquitin centered around the Ile 44 residue. It has also been shown that this same Ile 44 residue is necessary in the interaction between NEMO and polyubiquitin-K63 (Bloor S.
  • ubiquitin molecules are attached to the NEMO helix.
  • the ubiquitin molecules bind to the hydrophobic region of NOA whose binding site partially overlaps the ankyrin 1 D5.
  • the residue D304 of NOA is dipped in the center of the CC2-LZ / ubiquitin interface and forms H bonds with the H68 residue of ubiquitin.
  • the other main interactions involve non-polar residues including Ala 307, corresponding to the invariant residue AIa found in the IUIM motif and the residue F305 involved in the NEMO / polyubiquitin-K63 interaction. These interactions mask the hydrophobic surface of
  • the cDNA coding for the human CC2-LZ domain of NEMO called Tax CC2-LZ and ranging from Met 215 to Glu 362 (human numbering) is obtained by PCR using the following two nucleotide primers: NEMO 1 SEQ ID NO.8 ( 5'- CCCCATATGGAGCGCCAGGCCGCCTC) and NEMO 2 SEQ ID NO.9 (5'-TGAGGAAGCGGATGTCGAGTAGCTCGAGGGG).
  • This cDNA is introduced between the NdeI and XhoI restriction sites of a bacterial expression vector, pET-28b (Novagen) to generate the pET-NEMO vector.
  • the FLAG tag corresponding to the DYKDDDDK sequence is introduced into a pcDNA3 mammalian expression vector between the HindIII and EcoRI restriction sites to create the plasmid pcFLAG.
  • NEMO 3 SEQ ID No. 10 5'-GGGGAATTCTAATAGGCACCTCTGGAAGAG
  • NEMO 4 SEQ ID No. 11 5'-CATGGAGTGCATTGAGTAGCTCGAGGGG
  • the point mutations Glu296Ala, Phe312Ala, Glu315Ala, Ala323Pro and the double mutant Leu329Ala Leu336Ala are introduced firstly into the bacterial vector pET-NEMO-WT and secondly into the mammalian vector pcDNA3 / NEMO-WT using the technique site-directed mutagenesis, the protocol of which is described in the "Quikchange II Site-Directed Mutagenesis" kit from Stratagene.
  • Mouse embryonic fibroblasts (MEFs) deficient in NEMO are cultured in cell culture dishes and transiently transfected with a mixture containing: 0.2 ⁇ g of a plasmid pEF1 encoding ⁇ -galactosidase, 0.5 ⁇ g of a plasmid containing the reporter gene Ig-luciferase and 2 ⁇ g plasmids expressing the different variants of NEMO. Twenty four hours after transfection, the cells are activated with TNF ⁇ (20 ng / ml) for 24 h.
  • the cells are then recovered and then lysed in 110 ⁇ l of 25 mM Tris / Phosphate pH 7.8 buffer, 8 mM MgCl 2 , 1% Triton, 1 mM dithiothreitol, 15% glycerol to which a cocktail of proteases (Roche) is added.
  • the cell lysate is centrifuged at 13,000 rpm for 20 min at 4 ° C. The activity of the reporter gene is measured.
  • the purification of the various proteins is made from a culture of 3 liters of BL21-Gold D3 bacteria (Stratagene) transformed with the different plasmids pET 28 and in the presence of kanamycin (50 ⁇ g / ml). Protein expression is induced with 1mM IPTG at 37 ° C for 4 hours. After centrifugation for 20 min at 6000 g at 4 ° C., the bacteria are washed in 100 mM Tris / HCl pH 8 buffer containing 10 mM MgCl 2 . The bacterial pellets are frozen at -20 ° C.
  • the pellets are then resuspended in extraction buffer (50 mM Tris / HCl pH 8, 20 mM KCl and 5% glycerol) containing a mixture of protease inhibitors (Complete EDTA -free, Roche) at a rate of 2 ml / g of bacteria then crushed with a French Press at a pressure of 1500 psi.
  • the bacterial lysate undergoes 3 times 10 seconds of sonication at 90 W thus reducing the viscosity of the medium by fragmentation of the DNA.
  • the lysate is then diluted 2.5 times in 50 mM Tris / HCl buffer pH8, 1 M NaCl and centrifuged at 10,000 g for 30 min at 4 ° C.
  • the supernatant is then deposited on a 20 ml Ni-NTA Superflow affinity column (Qiagen) previously equilibrated in the previous buffer. After a night's washing of the column to remove all unbound proteins as well as DNA, the proteins are eluted by a linear gradient (0-500 mM) of imidazole (ACS, Merck) in the equilibration buffer of the column. The fractions containing the protein of interest are pooled and dialyzed against 20 mM HEPES buffer pH 7.5, 50 mM KCl, 1 mM EDTA. The dialysate whose pH is brought to 6 with
  • MES 1 M is loaded on a Poros 20-HS cation exchange column (Perseptive Biosystem) previously equilibrated in a 50 mM MES buffer pH6, 50 mM KCl. The elution is carried out by a linear gradient of KCl (50 mM-1 M). The protein fractions are combined and then concentrated by ultrafiltration (Amicon-Ultra with a cutoff of 10,000) and dialyzed against a buffer
  • the proteins are stored aliquoted at -80 ° C.
  • the purity of the various proteins is estimated to be> 98% according to the electrophoresis analysis under denaturing conditions and staining with Coomassie blue.
  • the protein concentration is determined by measuring the absorbance at 280 nm using a molar extinction coefficient of 5960 M ".
  • Chains A & B Nemo CC2LZ with numbering corresponding to entry 088522
  • Nemo aa M251 to L336 chain A starts at 242 and chain B at 247 (extra aa from the his tag) chains
  • C & D ankyrin 1D5 (yrs. 12 to 136)
  • ATOM 171 CA ALA A 263 58.057 30.460 233.712 .00 80.70 6
  • ATOM 254 CA ILE A 274 53.295 33.054 218.387 1.00 78.05 6
  • ATOM 361 C ISLE A 286 46.152 37.327 200.623 1.00 68.99 6
  • ATOM 402 CA PRO A 292 49.844 43.624 192.470 1..00 54.30 6
  • ATOM 642 CA TYR A 321 31.440 66.468 160.019 1.00 42.74 6
  • ATOM 662 CA GLN A 323 25.897 65.992 159.923 1.00 47.61 6
  • ATOM 680 CA GLN A 325 27.848 67.141 154.853 1.00 53.55 6
  • ATOM 812 CA ALA B 249 68.688 15.087 247.548 1.00 79.06 6

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Abstract

Cristal du domaine CC2-LZ de la protéine NEMO dont la structure tri¬ dimensionnelle a été déterminée par diffraction des rayons X à une résolution d'environ 3.25 A. La présente invention concerne également des méthodes de cristallisation du domaine CC2-LZ. Les cristaux de CC2-LZ ainsi que l'information dérivés de leurs structures cristallines sont utilisés pour identifier et concevoir des composés qui entrent en interaction avec CC2-LZ.

Description

STRUCTURE CRISTALLINE DU DOMAINE CC2-LZ DE NEMO
La présente invention a pour objet un cristal du domaine CC2-LZ de NEMO d'une taille et d'une qualité suffisante pour permettre d'obtenir des données structurelles par cristallographie par diffraction des rayons X.
L'invention concerne en particulier l'utilisation des données cristallographiques et de la structure tridimensionnelle du domaine CC2-LZ de NEMO pour identifier, modéliser et concevoir des composés modulant la voie de signalisation NF-κB.
La voie NF-κB est activée en réponse à divers stimuli extracellulaires tels que le LPS bactérien, des cytokines proinflammmatoires comme I1IL- 1 et le TNFα (M. S. Hayden and S. Ghosh, Signaling to NF-kappaB, Gènes Dev 18 (2004), no.18, 2195-2224). Les signaux sont généralement transmis depuis les récepteurs cellulaires jusqu'au complexe IKK, un régulateur pivot de la voie de signalisation
NF-κB. Le complexe IKK est composé de deux kinases IKKα et IKKβ et d'une protéine régulatrice NEMO (NF-κB essential modulator) (S. Yamaoka et al., Complémentation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation, CeII 93 (1998), no. 7, 1231-1240). NEMO joue un rôle crucial en intégrant les signaux provenant de divers stimuli et en induisant l'activation du complexe IKK.
La protéine NEMO est constituée dans sa portion N-terminale d'un domaine de liaison au complexe IKK et dans sa portion C-terminale d'un domaine d'oligomérisation (Figure 1). Notons que les protéines NEMO murine (SEQ ID
NO.1) et humaine (SEQ ID NO.2) ont une grande homologie de séquence à l'exception d'une insertion de 7 acides aminés dans la protéine humaine juste en amont d'un domaine spécifique, CC2.
L'activation du complexe IKK passe par un mécanisme lié à la capacité de la protéine NEMO de s'oligomériser par trans-activation via une kinase IKKK ou par trans-autoactivation via la dimérisation des kinases IKKs. A l'heure actuelle, le mécanisme d'activation du complexe IKK via NEMO n'est pas entièrement élucidé, bien que de nombreux rapports montrent que l'oligomérisation et la fixation aux polyubiquitines K-63 impliquant le domaine minimal CC2-LZ de NEMO jouent un rôle essentiel (J. L. Poyet et al., Activation of the IkappaB kinases by RIP via Ikkgamma/NEMO-mediated oligomerization, J
Biol Chem 275 (2000), no.48, 37966-37977) (F. Agou et al., Inhibition of NF- kappab activation by peptides targeting NF-kappaB essential modulator (NEMO) oligomerization, J Biol Chem 279 (2004), no.52, 54248-54257) (C. K. Ea et al., Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO, Mol CeII 22 (2006), no.2, 245-257) (C. J. Wu, et al., Sensing of lys 63-linked polyubiquitination by NEMO is a key event in NF- kappaB activation, Nat CeII Biol 8 (2006), no.4, 398-406). En effet, toutes les mutations localisées dans le CC2-LZ perturbant l'oligomérisation de NEMO ou la liaison aux chaînes de polyubiquitines K-63 (polyLJb K-63) inhibent l'activité IKK après stimulation par des cytokines (E. Vinolo et al., A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide- and tumor necrosis factor-mediated NF-kappaB activation, J Biol Chem 281 (2006), no.10, 6334-6348).
Le domaine minimal d'oligomérisation CC2-LZ de NEMO (aa 251-337 chez la souris, aa 258-344 chez l'homme) est composé de deux motifs successifs, un motif coiled-coil CC2 (aa 251-290 chez la souris, aa 258-297 chez l'homme) et un motif leucine zipper LZ (aa 293-337 chez la souris, aa 300-344 chez l'homme). On peut observer des variations de un à deux acides aminés aux extrémités du domaine CC2-LZ en fonction du logiciel utilisé pour la prédiction des structures CC2 et LZ.
Une fois activé, le complexe IKK phosphoryle des protéines IKB, déclenchant ainsi la dégradation de ces dernières par le protéasome 26S et libérant alors les facteurs de transcription NF-κB qui sont séquestrés dans le cytoplasme par les protéines IKB. Le facteur de transcription NF-κB migre alors dans le noyau et régule l'expression de gènes impliqués dans l'inflammation, l'immunité, l'apoptose et la survie cellulaire. L'activation constitutive de la voie NF-κB est impliquée dans l'oncogenèse. Elle est observée dans diverses tumeurs solides et leucémies, ainsi que dans des maladies autoimmunes et inflammatoires (D. S. Basseres and A. S. Baldwin, Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression, Oncogene 25 (2006), no.51 , 6817-6830) (M. S. Hayden et al., NF-kappaB and the immune response, Oncogene 25 (2006), no.51 , 6758-6780) (J. Inoue et al., NF-kappaB activation in development and progression of cancer, Cancer Sci 98 (2007), no.3, 268-274). Ainsi, le complexe IKK est apparu comme une cible très intéressante pour le développement de composés anti-inflammatoires et anti-tumorales (M. A. Calzado et al., NF-kappaB inhibitors for the treatment of inflammatory diseases and cancer, Curr Med Chem 14 (2007), no.3, 367-376) (T. D. Gilmore and M. Herscovitch, Inhibitors of NF-kappaB signaling: 785 and counting, Oncogene 25 (2006), no.51 , 6887-6899) (F. D'Acquisto et al., Inhibition of nuclear factor kappa
B (NF-kB): An emerging thème in anti-inflammatory thérapies, Mol Interv 2 (2002), no.1 , 22-35). La conception de composés ciblant NEMO plutôt que des kinases permet de supprimer sélectivement l'activité IKK stimuli-dépendante et de diminuer ainsi la cytotoxicité desdits composés.
Dans un effort pour élucider les mécanismes qui sous-tendent la régulation de la voie de signalisation NF-κB, la structure cristalline du complexe IKK, et en particulier de la protéine régulatrice NEMO, est étudiée. Par ailleurs, la connaissance de la structure tridimensionnelle est un atout essentiel pour établir les sites d'interaction avec les ligands résultant d'un criblage réel. Cette structure tridimensionnelle est également une source d'information dans l'approche par criblage virtuel ou modélisation in silico. Le processus de cristallisation de NEMO a été étudié, sans succès, par D.Gopaul et al., M.Delepierre et F.Cordier (non publiés). On peut citer en particulier les tentatives infructueuses de cristallisation du domaine CC2-LZ doté du motif de doigt de zinc (aa 251-412 de NEMO) ou sans ce motif (aa 251-388 de NEMO). Ces travaux pour obtenir des cristaux de - A -
Ia protéine NEMO et du domaine CC2-LZ en particulier ont donc été jusqu'alors sans succès.
La présente invention a donc pour but de proposer une nouvelle stratégie pour obtenir la cristallisation du domaine CC2-LZ de la protéine NEMO. Cette stratégie alternative est fondée sur une augmentation de la rigidité du domaine minimal d'oligomérisation de NEMO. La structure cristalline a été résolue par cristallographie par diffraction des rayons X avec une résolution de 3.25 A. Dans un second temps, la structure cristalline a été résolue par cristallographie par diffraction des rayons X avec une résolution de 2.9 A.
La présente invention concerne également les méthodes de cristallisation du domaine CC2-LZ. Les cristaux de CC2-LZ ainsi que l'information qui en dérive peuvent être analysés dans le but d'identifier ou de concevoir des composés qui entrent en interaction avec CC2-LZ.
La présente invention porte donc sur un cristal du domaine CC2-LZ de NEMO de mammifère dont le domaine peptidique CC2-LZ a la séquence d'acides aminés SEQ ID NO.3 et dont les variants peptidiques dérivent de ladite séquence d'acides aminés.
Dans le contexte de l'invention les termes « cristal », « cristal du domaine CC2- LZ », « cristal d'un complexe CC2-LZ » et « co-cristal du domaine CC2-LZ » sont utilisés indistinctement et se réfèrent à un cristal d'un complexe comprenant au moins deux entités distinctes. Une entité du cristal selon l'invention étant le domaine CC2-LZ ou l'un de ses variants.
La présente invention porte également sur un cristal d'un complexe du domaine CC2-LZ de NEMO de mammifère dont le domaine peptidique CC2-LZ a la séquence d'acides aminés SEQ ID NO.4 et dont les variants peptidiques dérivent de ladite séquence d'acides aminés. Par « séquence d'acides aminés », il doit être compris une séquence peptidique isolée du contexte naturel. Il s'agit notamment de séquences isolées, synthétisées chimiquement et/ou purifiées et éventuellement modifiées par génie génétique.
On entend par « variants » les séquences d'acides aminés des peptides décrits supra comprenant des substitutions conservatrices ou des mutations ponctuelles conservatrices et ayant essentiellement les mêmes propriétés que les peptides, respectivement, codés par les séquences SEQ ID NO.3 et SEQ ID NO.4, soit la capacité de s'oligomériser et de se fixer aux polyubiquitines K-63.
La présente invention porte, en outre, sur un cristal d'un complexe du domaine CC2-LZ de NEMO de mammifère dont les paramètres de la maille sont les suivants : - a=b=63.5 + 5 Â ;
- c=437.5 + 5 A ; et
- α=β=γ=90°; et le cristal a un groupe d'espace PAz2^2.
Conformément à l'acception usuelle dans le cadre de l'invention, l'expression
« paramètre de la maille » désigne les paramètres a, b et c de la maille cristalline correspondant aux longueurs des vecteurs non coplanaires de base (a, b, c), et les angles α, β et γ qui se forment entre les vecteurs (a, b, c). L'angle α est l'angle entre les vecteurs b et c, β celui entre les vecteurs a et c, et γ celui entre les vecteurs a et c. On entend par maille cristalline le parallélépipède construit par les vecteurs (a, b, c).
Les opérations de symétrie qui laissent globalement invariant un cristal, objet infini formé par la répétition d'un motif fini, constituent des groupes. Quand le cristal est à trois dimensions, on parle alors de « groupes d'espace ». Il doit être entendu que le cristal d'un complexe du domaine CC2-LZ selon la présente invention n'est pas limité au domaine CC2-LZ natif. En effet, le cristal d'un complexe selon l'invention comprend des mutants de CC2-LZ natif. Ces mutants sont obtenus par addition, délétion ou substitution d'au moins un acide aminé dans la séquence polypeptidique de CC2-LZ natif et ont substantiellement la même structure tridimensionnelle que celle du domaine CC2-LZ natif. On entend par « ayant substantiellement la même structure tridimensionnelle » le fait d'avoir un ensemble de coordonnées de structure atomique issues d'un cristal qui présentent une déviation moyenne inférieure ou égale à 5 A, de préférence à 2 A, lorsqu'on les superpose aux coordonnées de structure atomique de CC2-LZ natif de laquelle le mutant est dérivé lorsqu'au moins 50% à environ 100% des atomes de carbone alpha de CC2-LZ natif sont inclus dans la superposition.
L'invention porte, de manière préférée, sur un co-cristal, comprenant le domaine
CC2-LZ de NEMO de mammifère et au moins une ankyrine ou un fragment de celle-ci capable de stabiliser le complexe formé avec le domaine CC2-LZ, dont les paramètres de la maille sont les suivantes :
- a=b=63.5 ± 5 A ; - c=437.5 ± 5 A ; et
- α=β=γ=90°; et dont le co-cristal a un groupe d'espace P4s2i2.
On entend par « ankyrine » des protéines modulaires de tailles variables impliquées dans de multiples interactions protéine : protéine. Les ankyrines sont des protéines génétiquement conservées puisqu'on les retrouve chez les bactéries, les plantes, les champignons et les animaux et dont la structure est fondée à partir d'unités structurales répétitives d'environ 33 acides aminés. Un « fragment d'ankyrine » selon l'invention est capable de se lier et de stabiliser le complexe formé avec le domaine CC2-LZ de NEMO. De préférence, l'invention concerne un cristal du domaine CC2-LZ d'une protéine NEMO de mammifère et d'une ankyrine 1 D5 (SEQ ID NO.5). L'invention porte également sur un cristal du domaine CC2-LZ d'une protéine NEMO de mammifère et d'une ankyrine 2A1 ou 2F6 telle que décrite par Wyler et al. (Inhibition of NF-kappaB activation with designed ankyrin-repeat proteins targeting the ubiquitin-binding/oligomerization domain of NEMO, Protein Sci 16 (2007), no.9, 2013-2022).
En effet, afin de faciliter la cristallogenèse, le domaine CC2-LZ est complexé à une ankyrine 1 D5, qui se lie au CC2-LZ avec une forte affinité et rigidifie le domaine peptidique. Le profil de diffraction obtenu à partir des cristaux de CC2-
LZ complexé à l'ankyrine 1 D5 est utilisé pour déterminer la structure tridimensionnelle du CC2-LZ par remplacement moléculaire.
De préférence, l'ankyrine ou le fragment d'ankyrine est complexé au motif LZ du domaine CC2-LZ afin de, plus spécifiquement, le stabiliser. En effet, le motif LZ est plus flexible et thermodynamiquement plus instable que le motif CC2 du domaine CC2-LZ.
Le co-cristal du domaine CC2-LZ de NEMO avec une protéine d'ankyrine peut être obtenu par un procédé de cristallisation comprenant les étapes suivantes :
- incubation d'au moins une ankyrine ou d'un fragment d'ankyrine et du domaine CC2-LZ ;
- co-cristallisation du complexe protéique ankyrine ou fragment d'ankyrine/CC2-LZ par culture des cristaux par diffusion de vapeur. Dans un mode de réalisation préféré, le procédé de cristallisation de CC2-LZ correspond au procédé tel que décrit dans l'exemple 1.
De préférence, l'invention porte sur le cristal d'un complexe du domaine CC2-LZ de NEMO ou le co-cristal de CC2-LZ possédant les coordonnées cristallographiques décrites dans le tableau 1. De manière préférée, le cristal et le co-cristal du domaine CC2-LZ selon l'invention sont respectivement définis par leur structure tridimensionnelle obtenue par diffraction des rayons X laquelle est représentée figures 2 et 3.
La structure tridimensionnelle du CC2-LZ forme un dimère allongé composé de deux hélices α parallèles qui s'associent entre elles pour former une structure coiled-coil (Figure 2) (Figure 3). Le dimère de CC2-LZ interagit avec deux molécules d'ankyrines 1 D5, chaque ankyrine formant des contacts avec les hélices α sur les deux chaînes LZ. Trois résidus situés entre le motif CC2 et le motif LZ (aa 291-293, numérotation de souris) forment un pseudo coiled-coil. Le domaine de liaison aux chaînes de polyubiquitines K-63, qui est décrit dans Ea et al., est composé de 67 acides aminés (259-325 numérotation humaine, 252- 318 numérotation souris) correspondant à la région C-terminale du CC2 et la région N-terminale du LZ. Par recoupement des données issues de la structure tridimensionnelle, de la mutagenèse dirigée et de l'alignement de séquences du
CC2-LZ, la région formant le site de fixation aux ubiquitines a été déterminée entre les acides aminés 293 et 323 dans la séquence polypeptidique murine de NEMO (aa 300-330 numérotation humaine).
La structure tridimensionnelle du cristal et du co-cristal de CC2-LZ selon l'invention est obtenue par un procédé comprenant les étapes suivantes :
- l'obtention d'un cristal ou d'un co-cristal de la protéine CC2-LZ ;
- l'exposition du cristal aux rayons X ;
- la collecte des données de diffraction des rayons X ; - l'utilisation de ces données pour calculer la carte de densité électronique dudit cristal ;
- la construction et raffinement du modèle à partir de la carte de densité électronique.
Avantageusement, le procédé de détermination de la structure tridimensionnelle de CC2-LZ correspond au procédé tel que décrit dans l'exemple 1. L'invention s'étend également d'une part au cristal de la protéine murine de CC2-LZ comprenant la mutation Ala316Pro (A316P) et/ou la mutation Phe305Ala (F305A), et d'autre part au cristal de la protéine humaine de CC2-LZ comprenant également la mutation Ala323Pro (A323P) et/ou la mutation Phe312Ala (F312A).
Les différentes mutations obtenues par mutagenèse dirigée dans la protéine CC2- LZ humaine sont représentées Figure 4. La mutation Glu296Ala (E296A, position 289 chez la souris) est localisée à l'extrémité C-terminale du CC2 et est en dehors du site d'interaction aux ubiquitines (position aa 259-325, numérotation humaine et aa 252-318, numérotation souris). Les mutations Phe312Ala (F312A, position 305 chez la souris) et Glu315Ala (E315A, position 308 chez la souris) sont localisées dans le site de fixation aux ubiquitines. Les mutations Glu315Ala et Ala323Pro (A323P, position 316 chez la souris) sont respectivement impliquées dans deux pathologies humaines, la dysplasie ectodermique anhydrotique avec immunodéficience (EDA-ID) (R. Doffinger et al., Genetic heterogeneity of mendelian susceptibility to mycobacterial infection, Microbes Infect 2 (2000), no.13, 1553-1557) et \' incontinentia pigmenti (IP) (A. Smahi et al., Genomic rearrangement in nemo impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The international incontinentia pigmenti (IP) consortium,
Nature 405 (2000), no.6785, 466-472). La double mutation Leu329Ala Leu336Ala (L329A L336A, respectivement positions 322 et 329 chez la souris) est située dans le domaine leucine zipper du CC2-LZ.
Les capacités, de la protéine NEMO sauvage et des protéines NEMO mutantes définies supra, à restaurer l'activation de la voie NF-κB en réponse à la cytokine pro-inflammatoire TNF-α sont comparées et illustrées Figure 5. Pour ce faire, des fibroblastes embryonnaires de souris (MEF) déficients en NEMO sont co- transfectés de façon transitoire d'une part par le plasmide codant pour le gène rapporteur lgκ-luciférase, et d'autre part par les plasmides codant pour les différentes protéines, puis stimulés par du TNFα pendant 24 h. La protéine sauvage restaure complètement la voie NF-κB, alors que, l'activation TNFα- dépendante de la voie NF-κB est affectée à des degrés divers par les protéines mutantes. Les mutations A323P et F312A engendrent les deux plus fortes inhibitions, soit respectivement 95% et 78% d'inhibition. Pour la mutation A323P qui est à l'origine d'une forme sévère d'incontinentia pigmenti, un défaut de dimérisation de NEMO est à l'origine de l'inactivation de la voie NF-κB, résultat similaire à celui obtenu par Sebban-Benin et al. (Identification of TRAFΘ-dependent NEMO polyubiquitination sites through analysis of a new NEMO mutation causing incontinentia pigmenti, Hum Mo! Genêt 16 (2007), no.23, 2805-2815).
La protéine du domaine CC2-LZ de NEMO mutée en position F312A montre un profil d'élution, en filtration sur gel, identique à celui de la protéine CC2-LZ sauvage, indiquant que cette mutation n'affecte pas la stabilité du dimère mais modifie l'activation de la voie NF-κB (Figure 5). L'étude de ce mutant démontre pour la première fois que le défaut d'activation n'est pas dû à un défaut de dimérisation du site d'interaction aux ubiquitines mais à un défaut d'interaction avec les chaînes de polyubiquitines K63 comme montré par Ea et al. Par conséquent, ces résultats soulignent la possibilité d'inhiber la voie NF-κB soit en altérant la dimérisation de NEMO soit en inhibant l'interaction de NEMO avec les chaînes de polyubiquitines.
La présente invention permet d'une part la validation structurale par mutagenèse dirigée d'une conformation active de NEMO et d'autre part la détermination des résidus critiques pour l'oligomérisation de la protéine et par voie de conséquence pour l'activation du complexe IKK ainsi que ceux impliqués dans la fixation aux polyubiquitines K-63.
L'invention concerne de manière préférée une méthode d'identification de composés capables de se lier au domaine CC2-LZ de NEMO sur la base de données cristallographiques obtenues dans ladite invention. Des peptides mimant la séquence du CC2 ou du LZ sont montrés comme pouvant perturber roligomérisation de NEMO et ainsi supprimer l'activation de Ia voie NF-κB dans des cellules en culture. Avantageusement, l'invention porte sur l'élaboration et l'identification de composés interférant avec l'oligomérisation du domaine CC2- LZ inhibant la fixation dudit domaine aux polyubiquitines K-63.
Dans le contexte de l'invention on entend par « composés » toutes molécules chimiques inhibant la dimérisation du domaine CC2-LZ de NEMO ou inhibant l'interaction du domaine CC2-LZ de NEMO avec les chaînes polyubiquitines. Les données cristallographiques du domaine de NEMO ont donc permis de concevoir des peptides de haute affinité pour cette protéine. Les interactions CC2-
LZ : CC2-LZ permettant de former in vivo des complexes actifs de NEMO mettent en jeu de nombreuses liaisons non covalentes. La déstabilisation de ces complexes par des petites molécules étant très difficile à mettre en évidence dans un contexte de criblage à haut débit, il est nécessaire d'identifier une sonde peptidique mimant cette interaction, sur une portion réduite du peptide, et avec une affinité plus importante. Une telle sonde peptidique peut ensuite être marquée par un groupement fluorescent, et son association à CC2-LZ mise en évidence par une mesure de polarisation de fluorescence. Ce système permet de mettre en place dans un deuxième temps des campagnes de criblage à haut débit. Afin d'avoir une approche rationnelle et efficace pour créer cette sonde peptidique, la connaissance de la structure tridimensionnelle du domaine CC2-LZ est absolument indispensable. D'ores et déjà deux peptides appelés P8RD et PH4 ont été conçus sur ce principe (Figure 11).
Les sondes peptidiques selon l'invention sont de préférence le peptide PH4 et le peptide P8RD ayant les séquences en acides aminés respectives SEQ ID NO.6 et SEQ ID NO.7.
Le P8RD présente une affinité de 60 nM alors que le peptide PH4 a une affinité de 170 nM. Ces mesures sont effectuées à pH 7 et à température ambiante dans un tampon stringent correspondant à 20 mM Tris-Acétate-MES contenant 200 mM de chlorure de potassium et 0.5% Tween 20. Elles sont effectuées par polarisation de fluorescence à l'aide de peptides couplés en N-terminal avec des fluorophores Fluorescéine ou Cy5. Pour former les sondes peptidiques de l'invention, les peptides peuvent être couplés à toutes sortes de fluorophores.
La présente invention porte enfin sur une méthode d'identification de composés de la dimérisation de NEMO ou de l'interaction de NEMO avec les chaînes polyubiquitines entre une sonde peptidique selon l'invention et le domaine CC2- LZ de NEMO. Cette méthode de criblage à haut débit ou criblage HTS (High Throughput Screening) comprend les étapes suivantes :
- la mise en contact dudit peptide et dudit domaine CC2-LZ de NEMO ;
- l'ajout du composé à tester ;
- la mesure de la polarisation de fluorescence en présence du composé à tester ; - la comparaison de ladite mesure en l'absence du composé à tester.
Les relations structure-activité de ces peptides ainsi que la structure tridimensionnelle de la cible CC2-LZ de NEMO vont permettre de concevoir d'autres peptides avec des affinités de l'ordre du nM en privilégiant la zone d'interaction de NEMO pour l'ubiquitine et/ou les chaînes de polyubiquitines ayant des ramifications de toute nature (K63, K48, K6, N-terminale).
Le modèle du complexe du domaine CC2-LZ de NEMO/ubiquitine est représenté figures 7, 8 et 10. Par "modèle du complexe" on entend la structure tridimensionnelle du complexe CC2-LZ/ubiquitine.
Le modèle du complexe CC2-LZ de NEMO/ubiquitine a été construit sur la base des informations structurales obtenues à partir du complexe utilisé Rabex-5 ILJIM/ubiquitine (Lee S. et al. Structural basis for ubiquitin récognition and autoubiquitination by Rabex-5. Nat Struct Mol Biol 13, 264-271 , 2006). Le modèle du complexe CC2-LZ/ubiquitine a été vérifié expérimentalement grâce aux déplacements chimiques observés par RMN de l'interaction entre l'ubiquitine et le domaine CC2-LZ de NEMO (Figure 9).
La structure tridimensionnelle du domaine CC2-LZ de NEMO se déduit du modèle du complexe CC2-LZ/ubiquitine. Cette structure tridimensionnelle du CC2-LZ peut être utilisée pour la conception in silico ou criblage in silico de composés capables de se lier au domaine CC2-LZ de NEMO. La présente invention porte donc sur une méthode de conception de composés capables de se lier au domaine CC2-LZ de NEMO utilisant la structure tridimensionnelle du domaine CC2-LZ obtenue à partir des coordonnées cristallographiques du cristal selon l'invention.
Enfin, l'invention s'étend aux composés identifiés à partir des méthodes d'identification et de conception supra. De préférence ces composés inhibent la dimérisation du domaine CC2-LZ de NEMO ou inhibent l'interaction du domaine CC2-LZ de NEMO avec les chaînes polyubiquitines.
La présente invention est illustrée sans pour autant être limitée par les figures et exemples suivants :
Figure 1 : Représentation de la protéine NEMO.
Figure 2 : Structure tridimensionnelle du domaine CC2-LZ de NEMO complexé avec deux molécules d'ankyrines. Les deux sous-unités du
CC2-LZ sont en gris foncé tandis que les ankyrines sont en gris clair. Figure 3 : Structure du domaine CC2-LZ de NEMO dans le complexe avec les ankyrines 1 D5. Vu de côté du complexe en diagramme rubans. Les hélices de NEMO sont représentées en niveau de gris selon le domaine CC2, NOA ou LZ. Les chaînes d'ankyrines 1 D5 sont en gris foncé en position latérale.
Figure 4 : Localisation dans le domaine CC2-LZ humain des différentes mutations obtenues par mutagenèse dirigée. Le domaine de fixation aux polyubiquitines est représenté en blanc. La numérotation utilisée pour les acides aminés correspond à celle de la protéine humaine.
Figure 5 : Effet des différentes mutations sur l'activation de la voie NF- KB. La numérotation des mutations correspond à celle de la protéine humaine du CC2-LZ.
Figure 6: Modèle du complexe du domaine CC2-LZ de NEMO/ubiquitine. Séquence d'alignement entre le Rabex-5 (MIU/IUIM)(première ligne) et NEMO (motif NOA) (deuxième ligne) avec en-dessous les positions du motif structural de NOA (a-g). Les lignes verticales en trait continu et pointillé désignent respectivement des résidus identiques et similaires. La ligne diagonale indique des résidus spatialement similaire au vu du modèle structural selon l'invention. Les résidus strictement conservés dans le motif NOA sont indiqués par *. Figure 7: Vu de côté du complexe CC2-LZ de NEMO/ubiquitine. Les hélices de NEMO sont coloriées comme dans la figure 3. Les molécules d'ubiquitine sont en gris en position latérale et les molécules 1 D5 d'ankyrines du co-cristal sont en gris clair semi- transparent également en position latérale. Figure 8 : Vu rapproché de l'interface NOA/ubiquitine. Les résidus impliqués dans l'interaction sont dessinés dans une représentation de type "bail and stick" avec les atomes de carbone en gris (ubiquitine) et blanc (NEMO). Figure 9 : Déplacements chimiques observés par RMN de l'ubiquitine liée au domaine CC2-LZ de NEMO. Variations moyennes du déplacement chimique Δδav en fonction du résidu chimique. Les éléments de la structure secondaire correspondante sont représentés au dessus du graphe de déplacements chimiques. Figure 10 : Représentation de l'interaction entre l'ubiquitine et la région NOA du domaine CC2-LZ. Le gris foncé est utilisé pour les résidus intervenant dans une interaction forte. Les résidus d'ubiquitines sont représentés en gris clair pour 0,05<Δδav<0,085ppm. Figure 11: Séquences des peptides PH4 et P8RD qui ont été conçues en tenant compte de la structure cristallographique du domaine CC2- LZ. Les résidus soulignés et appartenant au N-cap ou au C-cap ont pour effet de stabiliser thermodynamiquement l'extrémité des hélices α en N-et en C-terminales.
EXEMPLE 1 : Structure cristallographique du domaine CC2-LZ
1.1 Construction des plasmides, expression et purification des protéines ankyrine 1 D5 et CC2-LZ
L'évolution de l'ankyrine 1 D5 est réalisée par ribosome display en utilisant la bibliothèque N2C DARPin (designed ankyrin repeat protein) (H. K. Binz et al., High-affinity binders selected from designed ankyrin repeat protein libraries, Nat Biotechnol 22 (2004), no.5, 575-582) pour Ia sélection. Les résultats de cette étude ainsi que les acides aminés de l'ankyrine 1D5 qui différent du modèle initial sont décrits dans la publication de Wyler et al. Le cDNA de l'ankyrine 1 D5 est clone dans le vecteur pQE30 (Qiagen) en phase avec une étiquette histidine située du côté N-terminal. Le plasmide pQE30-1 D5 est introduit dans une souche d'E. coli XL-1 blue et l'expression de la protéine 1 D5 est induite par ajout d'IPTG 1mM au milieu de culture pendant 3-3.5 heures à 37°C. Les bactéries sont récupérées par sédimentation, lavées en tampon Tris/HCI 50 mM pH 8 et lysées par sonication dans un tampon Tris/HCI 50 mM pH8, NaCI 0.5M (tampon A) en présence d'inhibiteurs de protéases (Complète free EDTA, Roche). L'extrait soluble est récupéré après centrifugation et chargé sur une colonne de nickel pré-équilibrée avec le tampon A. La protéine 1 D5 est éluée en utilisant un gradient linéaire d'imidazole. Les fractions contenant la protéine sont rassemblées puis dialysées contre un tampon 20 mM Tris/HCI pH 7,6, 50 mM KCI en utilisant des sacs de dialyse dont le seuil de coupure est de 6-8 kDa (Spectra/Por). La protéine est concentrée par ultrafiltration dans des tubes Amicon (Millipore) avec un seuil de coupure de 5 kDa.
Le domaine CC2-LZ (SEQ ID NO.3) (aa 251-337 de NEMO murin) est clone dans le plasmide pET28 en phase avec une étiquette histidine située du côté N- terminal. Ce domaine correspond aux résidus 258-344 de NEMO humain (SEQ ID NO.4). La protéine est exprimée dans une souche d'E. coli, BL21-gold (DE3), et purifiée sur une colonne de nickel comme décrit pour la purification de l'ankyrine 1 D5. La protéine CC2-LZ est ensuite purifiée sur une colonne échangeuse de cations, Poros 20-HS (Perseptive Biosystem). La colonne est pré-équilibrée dans le tampon 50 mM MES pH 7.1, 50 mM KCI et les protéines sont éluées par un gradient linéaire de KCI. Les fractions d'intérêt sont rassemblées et dialysées contre un tampon 2OmM Tris/HCI pH 8.0, 100 mM KCI, puis concentrées par ultrafiltration.
La pureté de la protéine est estimée supérieure à 98% d'après l'analyse par électrophorèse en conditions dénaturantes et coloration par du bleu de Coomassie. La concentration en protéine est déterminée par la méthode du Bradford et par mesure de l'absorption à 280 nm en utilisant un coefficient d'absorption de 2312 M"1cm"1 pour le CC2-LZ et 1490 M'1cm"1 pour l'1 D5.
Les protéines 1 D5 et CC2-LZ sont incubées ensemble pendant 30 min dans la glace et le complexe est purifié sur une colonne Superdex 200 HR (Pharmacia) équilibrée dans un tampon 20 mM Tris/HCI pH 8, 100 mM KCI. La stœchiométrie de liaison dans le complexe est de 1 :1. Le complexe est concentré par ultrafiltration afin d'obtenir une concentration en protéines de 10-13 mg/ml.
1.2 Conditions de cristallisation du complexe protéique ankyrine 1 D5 / CC2-LZ
Des cristaux ont poussé de façon reproductible dans deux conditions différentes
(Jena Bioscience ref :3A4 et 8B5). La solution réservoir 3A4 contient : 10% PEG 40000, 5% isopropanol,100 mM Na Hepes pH 7.5, et la solution 8B5 contient : 5% MPD (2-methyl-2,4-pentadiol), 5% éthanol, 100 mM Na Hepes pH7.5. Les cristaux ont poussé sous diffusion de vapeur dans des gouttelettes suspendues ensemencées avec des micro cristaux (microseeding). 1 μl du complexe protéique est ajouté à 1 μl de la solution réservoir et équilibré sous diffusion de vapeur à 18-200C pendant plus de 36 heures. Des micros cristaux (0.1 μl) obtenus à partir de fragment de cristaux sont introduits dans la goutte. Après l'ensemencement, les cristaux poussent en quelques jours pour atteindre une taille de 300x150x20μm. Pour la protection cryogénique, les cristaux sont plongés pendant 30 secondes dans la solution réservoir contenant en plus du
PEG 4000 et 20%C de glycérol pour le 3A4 ou 30% MPD pour le 8B5. Les cristaux sont montés sur des boucles de nylon et congelés très rapidement avant la collecte des données.
1.3 Analyse du complexe protéique ankyrine 1 D5 / CC2-LZ
Les données de diffraction aux rayons X (1=0.9794 A) sont enregistrées à l'aide du faisceau de rayonnement PX06SA au SLS (Source de Lumière Synchrotron Suisse) et d'un détecteur à pixels hybrides Pilatus 6M (distance cristal-détecteur, 640 mm et oscillations 0,5° par pas à 1000K). Les jeux de données sont traités avec la chaîne de programme XDS. Les cristaux appartiennent tous au même groupe d'espace P4β2i2 avec les paramètres de la maille cristalline suivant : a = b = 63.5 Λ et c = 437.5 A.
1.4 Détermination et affinement de la structure cristallographique du domaine
CC2-LZ de NEMO
La structure a été résolue par remplacement moléculaire en utilisant le programme AmoRe utilisant le modèle atomique de l'ankyrine 2JAB (Zhand et al, à paraître) et un modèle théorique pour les hélices de NEMO. Les données entre
15 et 3.5 A de résolution ont été utilisées pour ces calculs. Après analyse de la carte de densité électronique une construction manuelle du modèle a été entreprise en utilisant O. Un affinement avec TLS a été réalisé en utilisant le programme Refmac. Le modèle a été affiné en maintenant des contraintes de symétrie non cristallographiques pour l'ankyrine (chaîne C et D) et pour les hélices de NEMO (résidus 251 à 290, région N-terminale et résidus 294 à 337, région C-terminale). Le modèle final contient 26 molécules de solvant et une molécule de glycérol, avec une résolution RCo/stfRfœe de 20.8%/26.1% à 3,5 A. Les données stéréochimiques et les facteurs R sont présentés dans le tableau 1. La qualité stéréochimique du modèle a été analysée avec PRO-CHECK.
1.5 Obtention du modèle du complexe du domaine CC2-LZ de NEMO/ubiquitine
Les meilleurs candidats pour modéliser le complexe CC2-LZ/ubiquitine sont les structures comprenant une hélice α simple tel que I1UIM (ubiquitin-interacting motif) et I1UIM inversé (IUIM ou MIU) issu de Rabex-5. Après comparaison des séquences, il a été observé une identité de séquences d'environ 20% entre le motif NOA du domaine CC2-LZ et I1IUIM de Rabex-5 (Figure 6). Le motif IUIM de Rabex-5 se lie à la région hydrophobe de l'ubiquitine centrée autour du résidu Ile 44. il a également été montré que ce même résidu Ile 44 est nécessaire dans l'interaction entre NEMO et la polyubiquitine-K63 (Bloor S. et al. Signal processing by its coil zipper domain activâtes IKK gamma, Proc Natl Acad Sci USA 105, 1279-84, 2008), ce qui suggère clairement que l'ubiquitine se lie de manière équivalente au motif NOA de NEMO et au Rabex-5 IUIM. En conséquence, la structure tridimensionnelle connue du complexe Rabex-5 lUIM/ubiquitine a été utilisée comme guide dans l'élaboration du modèle du complexe CC2-LZ/ubiquitine.
Afin de respecter la symétrie, deux molécules d'ubiquitine sont fixées à l'hélice de NEMO. L'indice de complémentarité pour le complexe CC2-LZ/ubiquitine est de 0,69 soit supérieur à celui du complexe CC2-LZ/ankyrine 1 D5 (SC=0,65). Les molécules d'ubiquitine se lient à la région hydrophobe de NOA dont le site de liaison recouvre partiellement les ankyrines 1 D5. Le résidu D304 de NOA est plongé au centre de l'interface CC2-LZ/ubiquitine et forme des liaisons H avec le résidu H68 de l'ubiquitine. Les autres interactions principales impliquent des résidus non-polaires dont AIa 307, correspondant au résidu invariant AIa mis en évidence dans le motif IUIM et le résidu F305 impliqué dans l'interaction NEMO/polyubiquitine-K63. Ces interactions masquent la surface hydrophobe de
NOA, énergiquement défavorable, au solvant ce qui contribue à la stabilisation de cette région. La structure tridimensionnelle du modèle CC2-LZ/ubiquitine est par ailleurs vérifiée grâce à différentes expériences telles que la mutagenèse dirigée ou les déplacements chimiques observés par RMN (Figure 9).
Paramètres du cristal
Paramètres de la maille (A) a = b = 63.5 c =437.5
Groupe d'espace P432,2
Données de diffraction3
Température (K) 100
Gamme de résolution (A) 30-3.25
Réflexions observées (//0 (/)) 280,552 (15,169)
Réflexions uniques (/ 0 (I)) 28,729 (2,134)
Taux de remplissage (%) 99.1 (99.4)
P b 0.140 (0.449)
I / (I) 5.5 (1.7)
Monomères par unité asymétrique 2
Occupation du solvant (%) 73.3
Coefficient de Matthews (A3/Da) 4.6
Affinement
Résolution (A) 20-3.25
^factor 0.208
^free 0.261 rmsdc des longueurs de liaison (A) 0.013 rmsd des angles de liaison (°) 1.573
Diagramme de Ramachandran (%)
Résidus dans la conformation "Most favored" 91.8
Résidus dans la conformation "Additionally allowed" 8.0
Résidus dans la conformation "Generously allowed" 0.2
Résidus dans la conformation "Disallowed" 0.0
Jeux de données et affinement : a Valeurs entre parenthèses sont indiquées pour l'enveloppe de résolution externe : 3.43-3.25 A. bRsym = S |I-(I)|/S (I) , où I est l'intensité de mesure de chaque réflexion et (I) est l'intensité moyenne de cette réflexion, c (rmsd) Ecart quadratique moyen. EXEMPLE 2 : Validation structurale par mutagenèse dirigée d'une conformation active de NEMO
2.1 Construction des plasmides et mutagenèse dirigée
Le cDNA codant pour le domaine CC2-LZ humain de NEMO appelé Tax CC2-LZ et allant de la Met 215 au Glu 362 (numérotation humaine) est obtenu par PCR en utilisant les deux amorces nucléotidiques suivantes: NEMO 1 SEQ ID NO.8 (5'- CCCCATATGGAGCGCCAGGCCGCCTC) et NEMO 2 SEQ ID NO.9 (5'- TGAGGAAGCGGATGTCGAGTAGCTCGAGGGG). Ce cDNA est introduit entre les sites de restriction Ndel et Xhol d'un vecteur d'expression bactérien, pET-28b (Novagen) pour générer le vecteur pET-NEMO.
L'étiquette FLAG correspondant à la séquence DYKDDDDK est introduite dans un vecteur d'expression de mammifère pcDNA3 entre les sites de restriction Hindlll et EcoRI pour créer Ie plasmide pcFLAG.
Le cDNA codant pour la forme humaine de NEMO est amplifié par PCR avec les deux amorces nucléotidiques suivantes, NEMO 3 SEQ ID NO.10 (5'- GGGGAATTCTAATAGGCACCTCTGGAAGAG) et NEMO 4 SEQ ID NO.11 (5'- CATGGAGTGCATTGAGTAGCTCGAGGGG) puis introduit dans le plasmide pcFLAG entre les sites de restriction EcoRI et Xhol pour créer le plasmide pcNEMO-WT.
Les mutations ponctuelles Glu296Ala, Phe312Ala, Glu315Ala, Ala323Pro et le double mutant Leu329Ala Leu336Ala sont introduites d'une part dans le vecteur bactérien pET-NEMO-WT et d'autre part dans le vecteur de mammifère pcDNA3/NEMO-WT en utilisant la technique de mutagenèse dirigée dont le protocole est décrit dans le kit « Quikchange II Site-Directed Mutagenesis » de chez Stratagene.
2.2 Complémentation fonctionnelle dans des fibroblastes embryonnaires de souris Des fibroblastes embryonnaires de souris (MEF) déficients en NEMO sont cultivés en boites de culture cellulaire et transfectés transitoirement avec un mélange contenant : 0.2 μg d'un plasmide pEF1 codant pour la β-galactosidase, 0.5 μg d'un plasmide contenant le gène rapporteur Igk-luciférase et 2 μg des plasmides exprimant les différents variants de NEMO. Vingt quatre heures après la transfection, les cellules sont activées avec du TNFα (20 ng/ml) pendant 24 h. Les cellules sont alors récupérées puis lysées dans 110 μl de tampon 25 mM Tris/Phosphate pH 7,8, 8 mM MgCI2, 1% Triton, 1 mM dithiothréitol, 15% glycérol auquel est ajouté un cocktail de protéases (Roche). Le lysat cellulaire est centrifugé à 13 000 rpm pendant 20 min à 4°C. L'activité du gène rapporteur est mesurée.
2.3 Expressions et purifications de la protéine sauvage et du mutant F312A
La purification a est réalisée en utilisant un appareil AKTA Purifier 100 (Amersham
Pharmacia Biotech). La purification des différentes protéines est faite à partir d'une culture de 3 litres de bactéries BL21-Gold D3 (Stratagene) transformées avec les différents plasmides pET 28 et en présence de kanamycine (50 μg/ml). L'expression des protéines est induite avec 1mM d'IPTG à 37°C pendant 4 heures. Après centrifugation 20 min à 6000 g à 4°C, les bactéries sont lavées dans un tampon Tris/HCI 100 mM pH 8 contenant 10 mM MgCI2. Les culots bactériens sont congelés à -200C. Les culots sont ensuite resuspendus dans un tampon d'extraction (Tris/HCI 50 mM pH 8, KCI 20 mM et glycérol 5%) contenant un mélange d'inhibiteurs de protéases (Complète EDTA-free, Roche) à raison de 2 ml/g de bactéries puis broyées à l'aide d'une French Press sous une pression de 1500 psi. Le lysat bactérien subit 3 fois 10 secondes de sonication à 90 W permettant ainsi de diminuer la viscosité du milieu par fragmentation de l'ADN. Le lysat est alors dilué 2,5 fois dans un tampon Tris/HCI 50 mM pH8, NaCI 1 M puis centrifugé à 10 000 g pendant 30 min à 4°C. Le surnageant est ensuite déposé sur une colonne d'affinité Ni-NTA Superflow de 20 ml (Qiagen) préalablement équilibrée dans le tampon précédent. Après un lavage sur toute une nuit de la colonne pour éliminer toutes les protéines non accrochées ainsi que l'ADN, les protéines sont éluées par un gradient linéaire (0-500 mM) d'imidazole (ACS, Merck) dans le tampon d'équilibration de la colonne. Les fractions contenant la protéine d'intérêt sont rassemblées et dialysées contre un tampon HEPES 20 mM pH 7,5, KCI 50 mM, EDTA 1mM. Le dialysat dont le pH est amené à 6 avec du
MES 1 M est chargé sur une colonne échangeuse de cations Poros 20-HS (Perseptive Biosystem) préalablement équilibrée dans un tampon MES 50 mM pH6, KCI 50 mM. L'élution est effectuée par un gradient linéaire de KCI (50 mM-1 M). Les fractions protéiques sont réunies puis concentrées par ultrafiltration (Amicon-Ultra avec un seuil de coupure de 10 000) et dialysées contre un tampon
Tris/HCI 20 mM pH 8, KCI 100 mM. Les protéines sont conservées aliquotées à - 800C. La pureté des différentes protéines est estimée >98% d'après l'analyse par électrophorèse en conditions dénaturantes et coloration par du bleu de Coomassie. La concentration en protéine est déterminée par mesure de l'absorbance à 280 nm en utilisant un coefficient d'extinction molaire de 5960 M"
1Cm"1.
2.4 Filtration sur gel de la protéine sauvage et du mutant F312A
Les expériences de filtration sur gel sont réalisées à 40C sur une colonne
Superdex 75 HR 10/30 (Amersham Biosciences). La colonne est équilibrée dans un tampon Tris/HCI 50 mM pH7,5, NaCI 200 mM, DTE 0,2 mM à 4°C avec un débit de 0,5ml/min. Un échantillon de volume constant (200μl), à une concentration de 0.3 μM est injecté sur la colonne à un débit de 0,5ml/min. Les protéines sont diluées dans le tampon d'équilibration de la colonne et laissées à
4°C pendant 2 heures avant l'injection afin de les laisser s'équilibrer. Pour détecter l'élution des protéines, un spectrofluorimètre RF-10 AXL (Shimadzu) est branché en ligne sur l'appareil AKTA. La fluorescence intrinsèque est enregistrée en mesurant l'émission de fluorescence des résidus tyrosines à 310 nm après excitation à 280 nm. Tableau 1 :
Chains A & B = Nemo CC2LZ with numbering corresponding to entry 088522 Nemo aa = M251 to L336 chain A starts at 242 and chain B at 247 (extra aa from the his tag) chains C& D = ankyrin 1D5 (aa 12 to 136)
REMARK Wπtten by 0 version 11. 0.5
REMARK Fri Nov ! 3 11 :30:17 2007
CRYSTl 63 .499 63 .499 437.472 90.00 90.00 90.00
ORIGXl 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALEl 0.015748 0.000000 0.000000 0.00000
SCALE2 0.000000 0.015748 0.000000 0.00000
SCALE3 0.000000 0.000000 0.002286 0.00000
ATOM 1 N VAL A 242 56.460 37.782 235.855 1.00 91.30 7
ATOM 2 CA VAL A 242 57.909 38.147 235.886 1.00 90.83 6
ATOM 3 CB VAL A 242 58.315 39.047 234.639 1.00 90.87 6
ATOM 4 CGl VAL A 242 59.704 38.671 234.120 1.00 90.25 6
ATOM 5 CG2 VAL A 242 57.284 38.950 233.503 1.00 90.33 6
ATOM 6 C VAL A 242 58.376 38.794 237.240 1.00 90.98 6
ATOM 7 O VAL A 242 59.397 39.509 237.240 1.00 91.19 8
ATOM 8 N PRO A 243 57.655 38.548 238.390 1.00 90.67 7
ATOM 9 CA PRO A 243 58.202 39.037 239.689 1.00 90.27 6
ATOM 10 CB PRO A 243 57.126 38.653 240.723 1.00 90.07 6
ATOM 11 CG PRO A 243 56.375 37.540 240.096 1.00 90.45 6
ATOM 12 CD PRO A 243 56.371 37.842 238.596 1.00 90.65 6
ATOM 13 C PRO A 243 59.499 38.312 240.017 1.00 89.62 6
ATOM 14 O PRO A 243 59.553 37.077 239.966 1.00 89.75 8
ATOM 15 N ARG A 244 60.541 39.067 240.341 1.00 88.70 7
ATOM 16 CA ARG A 244 61.872 38.470 240.464 1.00 87.55 6
ATOM 17 CB ARG A 244 62.947 39.465 239.995 1.00 87.84 6
ATOM 18 CG ARG A 244 63.014 39.608 238.442 1.00 88.81 6
ATOM 19 CD ARG A 244 63.118 41.070 237.958 1.00 90.11 6
ATOM 20 NE ARG A 244 63.866 41.926 238.892 1.00 90.83 7
ATOM 21 CZ ARG A 244 64.326 43.151 238.622 1.00 90.77 6
ATOM 22 NHl ARG A 244 64.139 43.706 237.425 1.00 90.57 7
ATOM 23 NH2 ARG A 244 64.988 43.819 239.559 1.00 90.60 7
ATOM 24 C ARG A 244 62.142 37.865 241.857 1.00 86.31 6
ATOM 25 O ARG A 244 63.298 37.625 242.226 1.00 86.43 8
ATOM 26 N GLY A 245 61.057 37.604 242.605 1.00 84.69 7
ATOM 27 CA GLY A 245 61.092 36.869 243.883 1.00 82.05 6
ATOM 28 C GLY A 245 61.335 37.747 245.101 1.00 80.21 6
ATOM 29 O GLY A 245 62.456 37.794 245.628 1.00 80.36 8
ATOM 30 N SER A 246 60.286 38.426 245.565 1.00 77.76 7
ATOM 31 CA SER A 246 60.425 39.428 246.624 1.00 75.11 6
ATOM 32 CB SER A 246 59.634 40.689 246.220 1.00 75.41 6
ATOM 33 OG SER A 246 59.738 41.711 247.201 1.00 75.87 8
ATOM 34 C SER A 246 60.011 38.954 248.029 1.00 72.89 6
ATOM 35 0 SER A 246 59.422 39.727 248.773 1.00 72.73 8
ATOM 36 N HIS A 247 60.322 37.708 248.392 1.00 70.26 7
ATOM 37 CA HIS A 247 59.913 37.120 249.697 1.00 68.09 6
ATOM 38 CB HIS A 247 60.277 35.641 249.762 1.00 67.82 6
ATOM 39 CG HIS A 247 59.186 34.734 249.301 1.00 67.04 6 ATOM 40 NDl HIS A 247 58.145 34.350 250.118 00 66.33 7
ATOM 41 CEI HIS A 247 57.331 33.558 249.446 00 66.01 6
ATOM 42 NE2 HIS A 247 57.810 33.409 248.224 00 66.25 7
ATOM 43 CD2 HIS A 247 58.969 34.136 248.107 00 66.19 6
ATOM 44 C HIS A 247 60.439 37.801 250.974 00 66.82 6
ATOM 45 0 HIS A 247 61.560 38.276 251.027 00 66.82 8
ATOM 46 N MET A 248 59.632 37.847 252.018 00 65.13 7
ATOM 47 CA MET A 248 60.064 38.545 253.196 00 63.85 6
ATOM 48 CB MET A 248 58.872 39.115 253.929 00 63.42 6
ATOM 49 CG MET A 248 58.207 40.253 253.206 00 61.36 6
ATOM 50 SD MET A 248 58.774 41.914 253.596 00 57.47 16
ATOM 51 CE MET A 248 60.164 41.666 254.723 00 57.52 6
ATOM 52 C MET A 248 60.801 37.570 254.070 00 64.18 6
ATOM 53 0 MET A 248 61.670 37.954 254.840 00 64.07
ATOM 54 N ALA A 249 60.452 36.294 253.928 00 64.58 7
ATOM 55 CA ALA A 249 61.043 35.208 254.706 00 64.98 6
ATOM 56 CB ALA A 249 59.958 34.470 255.465 00 64.98
ATOM 57 C ALA A 249 61.812 34.241 253.811 00 65.59
ATOM 58 0 ALA A 249 62.166 34.563 252.674 00 65.95
ATOM 59 N SER A 250 62.059 33.042 254.310 00 66.12 7
ATOM 60 CA SER A 250 62.839 32.087 253.553 1.00 66.93 6
ATOM 61 CB SER A 250 63.744 31.314 254.508 1.00 66.17 6
ATOM 62 OG SER A 250 64.646 30.481 253.810 1.00 65.76
ATOM 63 C SER A 250 61.970 31.123 252.738 00 67.78
ATOM 64 0 SER A 250 61.227 30.342 253.310 00 68.10
ATOM 65 N MET A 251 62.056 31.178 251.410 00 68.65 7
ATOM 66 CA MET A 251 61.516 30.102 250.572 00 69.76 6
ATOM 67 CB MET A 251 60.218 30.531 249.884 00 69.79 6
ATOM 68 CG MET A 251 59.165 31.143 250.777 00 70.09 6
ATOM 69 SD MET A 251 58.290 29.962 251.810 00 71.12 16
ATOM 70 CE MET A 251 57.647 28.875 250.577 00 71.11 6
ATOM 71 C MET A 251 62.540 29.722 249.506 00 70.50 6
ATOM 72 0 MET A 251 62.395 30.116 248.350 00 70.57 8
ATOM 73 N GLN A 252 63.564 28.951 249.872 00 71.84 7
ATOM 74 CA GLN A 252 64.688 28.819 248.959 00 72.21 6
ATOM 75 CB GLN A 252 65.925 28.261 249.676 00 72.09 6
ATOM 76 CG GLN A 252 67.098 28.095 248.749 00 71.00 6
ATOM 77 CD GLN A 252 68.311 28.812 249.232 00 69.60 6
ATOM 78 OEl GLN A 252 69.065 28.298 250.045 00 70.22 8
ATOM 79 NE2 GLN A 252 68.523 30.007 248.720 00 69.23 7
ATOM 80 C GLN A 252 64.307 27.971 247.769 00 72.45 6
ATOM 81 0 GLN A 252 64.345 28.428 246.629 00 72.33 8
ATOM 82 N LEU A 253 63.933 26.738 248.090 1.00 72.90 7
ATOM 83 CA LEU A 253 63.577 25.691 247.155 1.00 73.09 6
ATOM 84 CB LEU A 253 63.357 24.395 247.949 1.00 72.61 6
ATOM 85 CG LEU A 253 62.668 23.226 247.256 00 71.41 6
ATOM 86 CDl LEU A 253 63.595 22.667 246.234 00 70.33 6
ATOM 87 CD2 LEU A 253 62.284 22.164 248.235 00 72.09 6
ATOM 88 C LEU A 253 62.276 26.054 246.483 00 73.74 6
ATOM 89 0 LEU A 253 62.118 25.996 245.254 00 73.87 8
ATOM 90 N GLU A 254 61.323 26.421 247.318 00 74.31 7
ATOM 91 CA GLU A 254 59.992 26.671 246.823 00 75.04 6
ATOM 92 CB GLU A 254 59.005 26.863 247.966 00 74.85 6
ATOM 93 CG GLU A 254 57.603 27.212 247.489 00 75.09 6
ATOM 94 CD GLU A 254 56.927 26.092 246.722 00 75.76 6
ATOM 95 OEl GLU A 254 56.661 25.012 247.298 1.00 76.58 ATOM 96 0E2 GLU A 254 56.644 26.301 245.532 1.00 75.99 8
ATOM 97 C GLU A 254 59.957 27.875 245.904 1.00 75.25 6
ATOM 98 O GLU A 254 59.127 27.941 244.996 1.00 75.30 8
ATOM 99 N ASP A 255 60.850 28.825 246.140 1.00 75.42 7
ATOM 100 CA ASP A 255 60.950 29.945 245.246 1.00 75.73 6
ATOM 101 CB ASP A 255 61.946 30.955 245.757 1.00 75.91 6
ATOM 102 CG ASP A 255 61.599 32.354 245.335 1.00 77.56 6
ATOM 103 ODl ASP A 255 61.563 32.620 244.112 1.00 79.25 8
ATOM 104 OD2 ASP A 255 61.348 33.195 246.227 1.00 79.41 8
ATOM 105 C ASP A 255 61.330 29.449 243.859 1.00 75.60 6
ATOM 106 O ASP A 255 60.526 29.514 242.933 1.00 75.72 8
ATOM 107 N LEU A 256 62.537 28.920 243.728 1.00 75.34 7
ATOM 108 CA LEU A 256 62.928 28.242 242.509 1.00 75.30 6
ATOM 109 CB LEU A 256 64.109 27.309 242.778 1.00 75.19 6
ATOM 110 CG LEU A 256 65.514 27.903 242.786 1.00 75.23 6
ATOM 111 CDl LEU A 256 66.534 26.772 242.738 1.00 75.17 6
ATOM 112 CD2 LEU A 256 65.729 28.881 241.617 1.00 74.99 6
ATOM 113 C LEU A 256 61.774 27.431 241.925 1.00 75.31 6
ATOM 114 0 LEU A 256 61.341 27.649 240.800 1.00 75.30 8
ATOM 115 N ARG A 257 61.272 26.501 242.718 1.00 75.47 7
ATOM 116 CA ARG A 257 60.233 25.586 242.290 1.00 75.75 6
ATOM 117 CB ARG A 257 59.745 24.788 243.507 1.00 75.66 6
ATOM 118 CG ARG A 257 59.159 23.466 243.150 1.00 75.77 6
ATOM 119 CD ARG A 257 58.663 22.720 244.350 1.00 75.78 6
ATOM 120 NE ARG A 257 58.741 21.305 244.035 1.00 77.55 7
ATOM 121 CZ ARG A 257 59.852 20.583 244.167 1.00 78.63 6
ATOM 122 NHl ARG A 257 60.954 21.149 244.635 1.00 78.96 7
ATOM 123 NH2 ARG A 257 59.871 19.296 243.840 1.00 78.95 7
ATOM 124 C ARG A 257 59.068 26.315 241.618 1.00 75.79 6
ATOM 125 0 ARG A 257 58.643 25.940 240.526 1.00 75.72 8
ATOM 126 N GLN A 258 58.558 27.350 242.280 1.00 76.03 7
ATOM 127 CA GLN A 258 57.466 28.152 241.729 1.00 76.53 6
ATOM 128 CB GLN A 258 56.919 29.156 242.741 1.00 76.59 6
ATOM 129 CG GLN A 258 55.526 28.841 243.261 1.00 78.00 6
ATOM 130 CD GLN A 258 55.383 29.164 244.762 1.00 80.85 6
ATOM 131 OEl GLN A 258 55.779 30.245 245.224 1.00 81.22 8
ATOM 132 NE2 GLN A 258 54.830 28.214 245.531 1.00 81.21 7
ATOM 133 C GLN A 258 57.916 28.906 240.496 1.00 76.57 6
ATOM 134 0 GLN A 258 57.408 28.678 239.411 1.00 76.75 8
ATOM 135 N GLN A 259 58.873 29.806 240.672 1.00 76.54 7
ATOM 136 CA GLN A 259 59.466 30.559 239.579 1.00 76.73 6
ATOM 137 CB GLN A 259 60.854 30.983 240.013 1.00 76.46 6
ATOM 138 CG GLN A 259 61.437 32.124 239.256 1.00 77.09 6
ATOM 139 CD GLN A 259 62.109 33.116 240.183 1.00 78.35 6
ATOM 140 OEl GLN A 259 62.761 32.735 241.153 1.00 79.03 8
ATOM 141 NE2 GLN A 259 61.941 34.403 239.898 1.00 79.78 7
ATOM 142 C GLN A 259 59.582 29.768 238.276 1.00 77.02 6
ATOM 143 0 GLN A 259 59.241 30.259 237.204 1.00 77.36 8
ATOM 144 N LEU A 260 60.087 28.547 238.385 1.00 77.32 7
ATOM 145 CA LEU A 260 60.234 27.628 237.266 1.00 77.61 6
ATOM 146 CB LEU A 260 60.851 26.319 237.778 1.00 77.46 6
ATOM 147 CG LEU A 260 61.475 25.205 236.920 1.00 77.15 6
ATOM 148 CDl LEU A 260 60.463 24.422 236.101 1.00 76.69 6
ATOM 149 CD2 LEU A 260 62.579 25.730 236.044 1.00 76.14 6
ATOM 150 C LEU A 260 58.881 27.332 236.660 1.00 78.11 6
ATOM 151 0 LEU A 260 58.634 27.600 235.489 1.00 78.27 8 ATOM 152 N GLN A 261 57.998 26.786 237.482 ,00 78.83 7
ATOM 153 CA GLN A 261 56.678 26.388 237.041 ,00 79.56 6
ATOM 154 CB GLN A 261 55.894 25.806 238.223 .00 79.87 6
ATOM 155 CG GLN A 261 55.317 24.406 237.970 ,00 81.14 6
ATOM 156 CD GLN A 261 53.927 24.449 237.344 ,00 82.68 6
ATOM 157 OEl GLN A 261 52.924 24.570 238.055 .00 83.22 8
ATOM 158 NE2 GLN A 261 53.861 24.343 236.013 ,00 82.41 7
ATOM 159 C GLN A 261 55.972 27.583 236.421 1.00 79.62 6
ATOM 160 0 GLN A 261 55.300 27.456 235.403 ,00 79.75 8
ATOM 161 N GLN A 262 56.171 28.753 237.011 ,00 79.91 7
ATOM 162 CA GLN A 262 55.520 29.942 236.513 ,00 80.58 6
ATOM 163 CB GLN A 262 55.553 31.086 237.533 .00 80.55 6
ATOM 164 CG GLN A 262 56.669 32.105 237.335 .00 81.54 6
ATOM 165 CD GLN A 262 56.384 33.438 238.010 .00 81.86 6
ATOM 166 OEl GLN A 262 55.735 33.495 239.066 1.00 83.81 8
ATOM 167 NE2 GLN A 262 56.872 34.526 237.404 1.00 82.80 7
ATOM 168 C GLN A 262 56.106 30.349 235.166 1.00 80.47 6
ATOM 169 0 GLN A 262 55.387 30.859 234.316 .00 80.72 8
ATOM 170 N ALA A 263 57.398 30.106 234.967 .00 80.53 7
ATOM 171 CA ALA A 263 58.057 30.460 233.712 .00 80.70 6
ATOM 172 CB ALA A 263 59.544 30.496 233.899 ,00 80.51 6
ATOM 173 C ALA A 263 57.688 29.497 232.588 ,00 80.85 6
ATOM 174 0 ALA A 263 57.431 29.908 231.466 .00 81.05
ATOM 175 N GLU A 264 57.664 28.213 232.902 ,00 81.06
ATOM 176 CA GLU A 264 57.188 27.197 231.979 .00 81.63
ATOM 177 CB GLU A 264 57.079 25.857 232.693 .00 81.60
ATOM 178 CG GLU A 264 58.146 24.850 232.314 .00 82.66
ATOM 179 CD GLU A 264 58.097 23.583 233.173 .00 82.90
ATOM 180 OEl GLU A 264 57.918 22.488 232.600 1.00 84.53
ATOM 181 0E2 GLU A 264 58.227 23.671 234.416 00 84.53
ATOM 182 C GLU A 264 55.818 27.523 231.444 00 81.51
ATOM 183 0 GLU A 264 55.570 27.414 230.245 00 81.74
ATOM 184 N GLU A 265 54.920 27.904 232.346 00 81.43 7
ATOM 185 CA GLU A 265 53.560 28.251 231.945 00 81.40 6
ATOM 186 CB GLU A 265 52.613 28.305 233.157 00 81.27 6
ATOM 187 CG GLU A 265 52.578 29.625 233.903 00 81.42 6
ATOM 188 CD GLU A 265 51.769 29.565 235.181 00 81.82 6
ATOM 189 OEl GLU A 265 51.485 30.641 235.749 00 82.88
ATOM 190 0E2 GLU A 265 51.422 28.450 235.627 00 82.41
ATOM 191 C GLU A 265 53.508 29.526 231.061 00 81.15
ATOM 192 0 GLU A 265 52.698 29.611 230.126 00 81.13
ATOM 193 N ALA A 266 54.390 30.484 231.355 00 80.69 7
ATOM 194 CA ALA A 266 54.572 31.683 230.551 00 80.22 6
ATOM 195 CB ALA A 266 55.623 32.567 231.176 00 80.03 6
ATOM 196 C ALA A 266 54.998 31.303 229.145 00 79.99 6
ATOM 197 0 ALA A 266 54.476 31.834 228.171 00 80.24 8
ATOM 198 N LEU A 267 55.947 30.380 229.039 00 79.60 7
ATOM 199 CA LEU A 267 56.433 29.930 227.737 00 79.38 6
ATOM 200 CB LEU A 267 57.411 28.769 227.876 00 79.44 6
ATOM 201 CG LEU A 267 58.871 28.994 228.257 00 79.42 6
ATOM 202 CDl LEU A 267 59.469 27.694 228.743 1.00 79.16 6
ATOM 203 CD2 LEU A 267 59.667 29.539 227.097 1.00 79.14 6
ATOM 204 C LEU A 267 55.316 29.452 226.841 1, 00 79.34 6
ATOM 205 0 LEU A 267 55.239 29.850 225.683 1.00 79.45 8
ATOM 206 N VAL A 268 54.467 28.573 227.366 1.00 79.21 7
ATOM 207 CA VAL A 268 53.361 28.030 226.572 1.00 79.04 6 ATOM 208 CB VAL A 268 52.613 26.883 227.300 1.00 78.93 6
ATOM 209 CGl VAL A 268 51.418 26.402 226.487 1.00 78.36 6
ATOM 210 CG2 VAL A 268 53.564 25.725 227.558 1.00 78.85 6
ATOM 211 C VAL A 268 52.424 29.161 226.157 1.00 79.09 6
ATOM 212 0 VAL A 268 52.099 29.294 224.985 1.00 79.08 8
ATOM 213 N ALA A 269 52.035 29.988 227.123 1.00 79.16 7
ATOM 214 CA ALA A 269 51.241 31.190 226.878 1.00 79.02 6
ATOM 215 CB ALA A 269 51.134 32.011 228.173 1.00 79.10 6
ATOM 216 C ALA A 269 51.790 32.044 225.712 1.00 78.94 6
ATOM 217 0 ALA A 269 51.016 32.524 224.875 1.00 78.93 8
ATOM 218 N LYS A 270 53.118 32.206 225.668 1.00 78.91 7
ATOM 219 CA LYS A 270 53.831 32.939 224.603 1.00 79.11 6
ATOM 220 CB LYS A 270 55.349 32.913 224.847 1.00 78.99 6
ATOM 221 CG LYS A 270 55.889 33.820 225.931 1.00 78.89 6
ATOM 222 CD LYS A 270 56.069 35.237 225.432 1.00 78.84 6
ATOM 223 CE LYS A 270 56.701 36.117 226.481 1.00 78.53 6
ATOM 224 NZ LYS A 270 58.147 35.838 226.532 1.00 78.40 7
ATOM 225 C LYS A 270 53.629 32.276 223.259 1.00 79.26 6
ATOM 226 0 LYS A 270 53.286 32.921 222.266 1.00 79.27 8
ATOM 227 N GLN A 271 53.900 30.977 223.239 1.00 79.44 7
ATOM 228 CA GLN A 271 53.703 30.146 222.065 1.00 79.70 6
ATOM 229 CB GLN A 271 54.020 28.702 222.410 1.00 79.72 6
ATOM 230 CG GLN A 271 54.034 27.800 221.212 1.00 79.95 6
ATOM 231 CD GLN A 271 55.299 27.960 220.416 1.00 80.65 6
ATOM 232 OEl GLN A 271 55.254 28.250 219.231 1.00 80.79 8
ATOM 233 NE2 GLN A 271 56.444 27.786 221.071 1.00 81.31 7
ATOM 234 C GLN A 271 52.275 30.214 221.508 1.00 79.85 6
ATOM 235 0 GLN A 271 52.092 30.352 220.305 1.00 79.94 8
ATOM 236 N GLU A 272 51.274 30.090 222.386 1.00 79.87 7
ATOM 237 CA GLU A 272 49.872 30.333 222.036 1.00 79.75 6
ATOM 238 CB GLU A 272 49.032 30.636 223.279 1.00 79.91 6
ATOM 239 CG GLU A 272 47.978 29.614 223.638 1.00 81.15 6
ATOM 240 CD GLU A 272 48.506 28.534 224.572 1.00 83.38 6
ATOM 241 OEl GLU A 272 48.181 28.556 225.788 1.00 84.07 8
ATOM 242 0E2 GLU A 272 49.261 27.661 224.090 1.00 84.41 8
ATOM 243 C GLU A 272 49.788 31.543 221.137 1.00 79.48 6
ATOM 244 0 GLU A 272 49.121 31.493 220.103 1.00 79.55 8
ATOM 245 N LEU A 273 50.469 32.621 221.554 1.00 79.02 7
ATOM 246 CA LEU A 273 50.489 33.901 220.839 1.00 78.51 6
ATOM 247 CB LEU A 273 51.075 35.027 221.700 1.00 78.34 6
ATOM 248 CG LEU A 273 51.318 36.343 220.934 1.00 77.65 6
ATOM 249 CDl LEU A 273 50.001 37.038 220.616 1.00 77.55 6
ATOM 250 CD2 LEU A 273 52.256 37.287 221.655 1.00 77.81 6
ATOM 251 C LEU A 273 51.279 33.840 219.538 1.00 78.55 6
ATOM 252 0 LEU A 273 50.829 34.371 218.512 1.00 78.74 8
ATOM 253 N ILE A 274 52.465 33.230 219.588 1.00 78.25 7
ATOM 254 CA ILE A 274 53.295 33.054 218.387 1.00 78.05 6
ATOM 255 CB ILE A 274 54.445 32.022 218.582 1.00 78.15 6
ATOM 256 CGl ILE A 274 55.511 32.529 219.564 1.00 78.91 6
ATOM 257 CD ILE A 274 56.444 33.614 218.999 1.00 79.68 6
ATOM 258 CG2 ILE A 274 55.066 31.632 217.230 1.00 77.06 6
ATOM 259 C ILE A 274 52.461 32.491 217.263 1.00 77.87 6
ATOM 260 0 ILE A 274 52.391 33.070 216.193 1.00 78.12 8
ATOM 261 N ASP A 275 51.823 31.358 217.527 1.00 77.57 7
ATOM 262 CA ASP A 275 51.070 30.627 216.517 1.00 77.32 6
ATOM 263 CB ASP A 275 50 . 685 29 . 250 217 . 037 1 . 00 77 . 35 ATOM 264 CG ASP A 275 51.817 28.588 217.776 1.00 78.33 6
ATOM 265 ODl ASP A 275 52.971 29.024 217.561 1.00 79.48 8
ATOM 266 0D2 ASP A 275 51.569 27.661 218.584 1.00 78.95 8
ATOM 267 C ASP A 275 49.831 31.368 216.064 1.00 77.10 6
ATOM 268 O ASP A 275 49.457 31.274 214.903 1.00 77.23 8
ATOM 269 N LYS A 276 49.191 32.093 216.979 1.00 76.72 7
ATOM 270 CA LYS A 276 48.073 32.965 216.638 1.00 76.28 6
ATOM 271 CB LYS A 276 47.521 33.630 217.906 1.00 76.24 6
ATOM 272 CG LYS A 276 46.711 34.912 217.702 1.00 76.46 6
ATOM 273 CD LYS A 276 45.266 34.785 218.154 1.00 76.27 6
ATOM 274 CE LYS A 276 44.766 36.135 218.644 1.00 76.13 6
ATOM 275 NZ LYS A 276 43.317 36.130 218.942 1.00 76.37 7
ATOM 276 C LYS A 276 48.557 34.001 215.631 1.00 75.92 6
ATOM 277 0 LYS A 276 47.882 34.264 214.638 1.00 76.06 8
ATOM 278 N LEU A 277 49.744 34.552 215.887 1.00 75.43 7
ATOM 279 CA LEU A 277 50.347 35.606 215.071 1.00 75.07 6
ATOM 280 CB LEU A 277 51.524 36.242 215.822 1.00 74.81 6
ATOM 281 CG LEU A 277 51.343 37.516 216.648 1.00 74.54 6
ATOM 282 CDl LEU A 277 52.698 38.142 216.886 1.00 73.76 6
ATOM 283 CD2 LEU A 277 50.410 38.536 215.974 1.00 75.19 6
ATOM 284 C LEU A 277 50.853 35.108 213.727 1.00 74.91 6
ATOM 285 O LEU A 277 50.693 35.771 212.693 1.00 74.85 8
ATOM 286 N LYS A 278 51.506 33.953 213.781 1.00 74.84 7
ATOM 287 CA LYS A 278 52.032 33.249 212.621 1.00 74.86 6
ATOM 288 CB LYS A 278 52.538 31.857 213.057 1.00 74.63 6
ATOM 289 CG LYS A 278 53.711 31.258 212.282 1.00 73.54 6
ATOM 290 CD LYS A 278 55.041 31.768 212.820 1.00 72.18 6
ATOM 291 CE LYS A 278 56.250 31.072 212.205 1.00 71.59 6
ATOM 292 NZ LYS A 278 56.872 30.043 213.087 1.00 70.31 7
ATOM 293 C LYS A 278 50.879 33.064 211.664 1.00 75.25 6
ATOM 294 0 LYS A 278 50.921 33.503 210.517 1.00 75.38 8
ATOM 295 N GLU A 279 49.827 32.444 212.177 1.00 75.64 7
ATOM 296 CA GLU A 279 48.639 32.143 211.414 1.00 76.14 6
ATOM 297 CB GLU A 279 47.713 31.285 212.249 1.00 76.14 6
ATOM 298 CG GLU A 279 46.620 30.605 211.479 1.00 77.32 6
ATOM 299 CD GLU A 279 45.497 30.185 212.395 1.00 79.14 6
ATOM 300 OEl GLU A 279 44.382 30.722 212.233 1.00 80.40 8
ATOM 301 0E2 GLU A 279 45.730 29.346 213.298 1.00 79.74 8
ATOM 302 C GLU A 279 47.903 33.392 210.939 1.00 76.23 6
ATOM 303 O GLU A 279 47.401 33.414 209.830 1.00 76.56 8
ATOM 304 N GLU A 280 47.825 34.425 211.770 1.00 76.32 7
ATOM 305 CA GLU A 280 47.206 35.672 211.348 1.00 76.38 6
ATOM 306 CB GLU A 280 47.170 36.675 212.489 1.00 76.35 6
ATOM 307 CG GLU A 280 45.956 36.539 213.381 1.00 76.80 6
ATOM 308 CD GLU A 280 46.104 37.297 214.691 1.00 77.93 6
ATOM 309 OEl GLU A 280 45.309 37.030 215.618 1.00 78.26 8
ATOM 310 0E2 GLU A 280 47.013 38.156 214.803 1.00 78.36 8
ATOM 311 C GLU A 280 47.962 36.261 210.172 1.00 76.62 6
ATOM 312 0 GLU A 280 47.357 36.647 209.167 1.00 76.82 8
ATOM 313 N ALA A 281 49.288 36.309 210.297 1.00 76.86 7
ATOM 314 CA ALA A 281 50.169 36.795 209.230 1.00 76.99 6
ATOM 315 CB ALA A 281 51.630 36.757 209.682 1.00 77.14 6
ATOM 316 C ALA A 281 49.986 35.995 207.946 1.00 76.96 6
ATOM 317 O ALA A 281 50.338 36.453 206.863 1.00 77.04 8
ATOM 318 N GLU A 282 49.421 34.802 208.076 1.00 76.98 7
ATOM 319 CA GLU A 282 49.109 33.975 206.920 1.00 77.23 6 ATOM 320 CB GLU A 282 48.728 32.557 207.341 1.00 77.37 6
ATOM 321 CG GLU A 282 48.950 31.533 206.257 1.00 78.61 6
ATOM 322 CD GLU A 282 50.385 31.552 205.750 1.00 80.14 6
ATOM 323 OEl GLU A 282 51.248 30.934 206.411 1.00 79.79 8
ATOM 324 0E2 GLU A 282 50.645 32.191 204.699 1.00 81.09 8
ATOM 325 C GLU A 282 47.997 34.556 206.059 1.00 77.07 6
ATOM 326 0 GLU A 282 48.166 34.681 204.850 1.00 77.14 8
ATOM 327 N GLN A 283 46.858 34.883 206.673 1.00 76.94 7
ATOM 328 CA GLN A 283 45.745 35.504 205.938 1.00 76.81 6
ATOM 329 CB GLN A 283 44.414 35.488 206.699 1.00 77.00 6
ATOM 330 CG GLN A 283 43.709 34.155 206.792 1.00 77.77 6
ATOM 331 CD GLN A 283 43.587 33.683 208.240 1.00 79.45 6
ATOM 332 OEl GLN A 283 44.174 34.268 209.166 1.00 78.97 8
ATOM 333 NE2 GLN A 283 42.810 32.623 208.445 1.00 80.36 7
ATOM 334 C GLN A 283 46.025 36.945 205.553 1.00 76.35 6
ATOM 335 0 GLN A 283 45.320 37.492 204.692 1.00 76.38 8
ATOM 336 N HIS A 284 47.010 37.572 206.208 1.00 75.63 7
ATOM 337 CA HIS A 284 47.465 38.911 205.801 1.00 75.04 6
ATOM 338 CB HIS A 284 48.363 39.586 206.848 1.00 75.13 6
ATOM 339 CG HIS A 284 47.776 39.663 208.224 1.00 75.41 6
ATOM 340 NDl HIS A 284 46.419 39.736 208.461 1.00 75.59 7
ATOM 341 CEI HIS A 284 46.205 39.806 209.764 1.00 15.11 6
ATOM 342 NE2 HIS A 284 47.374 39.797 210.379 1.00 75.45 7
ATOM 343 CD2 HIS A 284 48.373 39.721 209.440 1.00 75.13 6
ATOM 344 C HIS A 284 48.242 38.783 204.497 1.00 74.47 6
ATOM 345 0 HIS A 284 48.038 39.563 203.555 1.00 74.34 8
ATOM 346 N LYS A 285 49.132 37.785 204.474 1.00 73.59 7
ATOM 347 CA LYS A 285 49.900 37.396 203.296 1.00 72.73 6
ATOM 348 CB LYS A 285 50.613 36.058 203.587 1.00 72.85 6
ATOM 349 CG LYS A 285 51.725 35.615 202.619 1.00 73.74 6
ATOM 350 CD LYS A 285 51.203 34.897 201.338 1.00 75.10 6
ATOM 351 CE LYS A 285 50.670 33.452 201.571 1.00 75.35 6
ATOM 352 NZ LYS A 285 51.708 32.376 201.505 1.00 75.28 7
ATOM 353 C LYS A 285 48.956 37.282 202.089 1.00 71.80 6
ATOM 354 0 LYS A 285 49.143 37.962 201.083 1.00 71.76 8
ATOM 355 N ILE A 286 47.913 36.467 202.240 1.00 70.67 7
ATOM 356 CA ILE A 286 46.969 36.136 201.166 1.00 69.68 6
ATOM 357 CB ILE A 286 46.022 34.950 201.583 1.00 69.69 6
ATOM 358 CGl ILE A 286 45.974 33.871 200.476 1.00 70.28 6
ATOM 359 CD ILE A 286 46.242 32.400 200.943 1.00 70.18 6
ATOM 360 CG2 ILE A 286 44.626 35.452 201.967 1.00 68.83 6
ATOM 361 C ILE A 286 46.152 37.327 200.623 1.00 68.99 6
ATOM 362 0 ILE A 286 45.689 37.314 199.478 1.00 69.02 8
ATOM 363 N VAL A 287 45.974 38.353 201.442 1.00 68.04 7
ATOM 364 CA VAL A 287 45.303 39.572 200.999 1.00 67.05 6
ATOM 365 CB VAL A 287 44.651 40.305 202.211 1.00 67.04 6
ATOM 366 CGl VAL A 287 44.677 41.813 202.060 1.00 66.05 6
ATOM 367 CG2 VAL A 287 43.240 39.812 202.418 1.00 66.88 6
ATOM 368 C VAL A 287 46.290 40.473 200.248 1.00 66.58 6
ATOM 369 0 VAL A 287 45.960 41.049 199.216 1.00 66.54 8
ATOM 370 N MET A 288 47.508 40.570 200.776 1.00 65.76 7
ATOM 371 CA MET A 288 48.574 41.382 200.195 1.00 64.98 6
ATOM 372 CB MET A 288 49.837 41.251 201.041 1.00 64.94 6
ATOM 373 CG MET A 288 49.663 41.683 202.469 1.00 65.34 6
ATOM 374 SD MET A 288 51.073 41.339 203.554 1.00 66.03 16
ATOM 375 CE MET A 288 52.398 42.312 202.814 1.00 65.40 6 ATOM 376 C MET A 288 48.901 40.957 198.772 .00 63.99
ATOM 377 0 MET A 288 49.336 41.774 197.960 .00 63.69
ATOM 378 N GLU A 289 48.708 39.668 198.496 .00 62.98 7
ATOM 379 CA GLU A 289 48.910 39.093 197.170 .00 62.17 6
ATOM 380 CB GLU A 289 48.692 37.597 197.204 .00 62.12 6
ATOM 381 CG GLU A 289 49.887 36.818 197.635 1.00 64.01 6
ATOM 382 CD GLU A 289 49.570 35.340 197.706 .00 67.40 6
ATOM 383 OEl GLU A 289 48.640 34.925 196.960 .00 67.38
ATOM 384 0E2 GLU A 289 50.230 34.602 198.502 .00 68.10
ATOM 385 C GLU A 289 47.946 39.674 196.148 .00 61.13
ATOM 386 O GLU A 289 48.171 39.577 194.931 .00 61.18
ATOM 387 N THR A 290 46.862 40.264 196.639 .00 59.59 7
ATOM 388 CA THR A 290 45.918 40.933 195.759 1.00 57.74 6
ATOM 389 CB THR A 290 44.479 40.944 196.314 1.00 57.49 6
ATOM 390 OGl THR A 290 44.310 42.073 197.164 1..00 55.48 8
ATOM 391 CG2 THR A 290 44.181 39.683 197.080 1..00 57.71 6
ATOM 392 C THR A 290 46.284 42.395 195.384 1, .00 57.47 6
ATOM 393 0 THR A 290 45.584 42.952 194.540 1. ,00 57.42
ATOM 394 N VAL A 291 47.321 43.026 196.001 1. ,00 56.52
ATOM 395 CA VAL A 291 47.780 44.393 195.641 1. ,00 55.85
ATOM 396 CB VAL A 291 48.712 44.988 196.702 1. ,00 55.32 6
ATOM 397 CGl VAL A 291 49.267 46.338 196.264 1. ,00 55.05 6
ATOM 398 CG2 VAL A 291 47.952 45.150 197.972 1. ,00 54.94 6
ATOM 399 C VAL A 291 48.317 44.488 194.193 1..00 55.56 6
ATOM 400 0 VAL A 291 47.738 45.240 193.382 1..00 55.78 8
ATOM 401 N PRO A 292 49.354 43.686 193.842 1..00 54.84 7
ATOM 402 CA PRO A 292 49.844 43.624 192.470 1..00 54.30 6
ATOM 403 CB PRO A 292 50.684 42.345 192.472 1..00 54.40
ATOM 404 CG PRO A 292 50.287 41.623 193.719 1..00 54.58
ATOM 405 CD PRO A 292 50.062 42.716 194.682 1..00 54.67 6
ATOM 406 C PRO A 292 48.664 43.468 191.510 1. ,00 53.71 6
ATOM 407 O PRO A 292 48.637 44.116 190.447 1. ,00 53.44 8
ATOM 408 N VAL A 293 47.696 42.634 191.918 1. ,00 53.07 7
ATOM 409 CA VAL A 293 46.443 42.388 191.166 1..00 52.68 6
ATOM 410 CB VAL A 293 45.502 41.307 191.857 1..00 52.23 6
ATOM 411 CGl VAL A 293 44.050 41.422 191.398 1..00 51.71 6
ATOM 412 CG2 VAL A 293 45.974 39.922 191.590 1..00 51.88 6
ATOM 413 C VAL A 293 45.643 43.677 190.958 1.00 52.54 6
ATOM 414 0 VAL A 293 45.336 44.086 189.825 1.00 52.34 8
ATOM 415 N LEU A 294 45.293 44.317 192.067 1 ,00 52.20 7
ATOM 416 CA LEU A 294 44.479 45.517 191.965 1 ,00 51.54 6
ATOM 417 CB LEU A 294 43.831 45.937 193.295 1 ,00 51.62 6
ATOM 418 CG LEU A 294 42.763 44.985 193.872 1 ,00 51.19 6
ATOM 419 CDl LEU A 294 41.850 45.694 194.839 1.00 48.66 6
ATOM 420 CD2 LEU A 294 41.942 44.312 192.761 ,00 52.36 6
ATOM 421 C LEU A 294 45.233 46.645 191.282 .00 51.21 6
ATOM 422 0 LEU A 294 44.653 47.320 190.456 .00 51.20 8
ATOM 423 N LYS A 295 46.525 46.818 191.576 ,00 50.73 7
ATOM 424 CA LYS A 295 47.325 47.786 190.837 .00 50.37 6
ATOM 425 CB LYS A 295 48.789 47.692 191.272 .00 50.63 6
ATOM 426 CG LYS A 295 49.533 49.026 191.280 .00 52.16 6
ATOM 427 CD LYS A 295 49.194 49.934 192.516 ,00 54.46 6
ATOM 428 CE LYS A 295 49.806 49.444 193.874 .00 54.25 6
ATOM 429 NZ LYS A 295 51.231 49.832 194.136 ,00 53.36 7
ATOM 430 C LYS A 295 47.140 47.524 189.331 1.00 49.83 6
ATOM 431 0 LYS A 295 46.723 48.408 188.591 1.00 49.39 8 ATOM 432 N ALA A 296 47.394 46.282 188.914 1.00 49.63 7
ATOM 433 CA ALA A 296 47.344 45.898 187.506 1.00 49.30 6
ATOM 434 CB ALA A 296 47.671 44.420 187.310 1.00 49.17 6
ATOM 435 C ALA A 296 45.981 46.221 186.938 1.00 49.22 6
ATOM 436 0 ALA A 296 45.894 46.820 185.872 1.00 49.72 8
ATOM 437 N GLN A 297 44.906 45.857 187.634 1.00 48.90 7
ATOM 438 CA GLN A 297 43.581 46.189 187.087 1.00 48.85 6
ATOM 439 CB GLN A 297 42.404 45.770 187.964 1.00 48.94 6
ATOM 440 CG GLN A 297 41.092 46.537 187.610 1.00 49.31 6
ATOM 441 CD GLN A 297 39.894 46.206 188.516 1.00 50.34 6
ATOM 442 OEl GLN A 297 38.945 46.995 188.622 1.00 51.69 8
ATOM 443 NE2 GLN A 297 39.934 45.038 189.169 1.00 51.71 7
ATOM 444 C GLN A 297 43.469 47.675 186.861 1.00 48.33 6
ATOM 445 0 GLN A 297 43.156 48.104 185.756 1.00 48.54 8
ATOM 446 N ALA A 298 43.719 48.457 187.909 1.00 47.62 7
ATOM 447 CA ALA A 298 43.595 49.906 187.813 1.00 46.90 6
ATOM 448 CB ALA A 298 44.085 50.610 189.069 1.00 46.71 6
ATOM 449 C ALA A 298 44.327 50.405 186.585 1.00 46.57 6
ATOM 450 0 ALA A 298 43.726 51.062 185.753 1.00 46.74 8
ATOM 451 N ASP A 299 45.600 50.057 186.438 1.00 46.08 7
ATOM 452 CA ASP A 299 46.352 50.478 185.260 1.00 45.84 6
ATOM 453 CB ASP A 299 47.792 49.971 185.301 1.00 46.19 6
ATOM 454 CG ASP A 299 48.480 50.295 186.603 1.00 47.23 6
ATOM 455 ODl ASP A 299 48.105 51.324 187.224 1.00 48.55 8
ATOM 456 0D2 ASP A 299 49.382 49.514 186.998 1.00 47.75 8
ATOM 457 C ASP A 299 45.687 50.041 183.963 1.00 45.16 6
ATOM 458 0 ASP A 299 45.474 50.867 183.069 1.00 45.25 8
ATOM 459 N ILE A 300 45.346 48.757 183.869 1.00 44.18 7
ATOM 460 CA ILE A 300 44.756 48.222 182.649 1.00 43.77 6
ATOM 461 CB ILE A 300 44.418 46.736 182.775 1.00 43.73 6
ATOM 462 CGl ILE A 300 45.609 45.904 182.329 1.00 44.04 6
ATOM 463 CD ILE A 300 45.685 44.592 183.042 1.00 44.89 6
ATOM 464 CG2 ILE A 300 43.274 46.359 181.875 1.00 43.73 6
ATOM 465 C ILE A 300 43.532 49.015 182.245 1.00 43.59 6
ATOM 466 0 ILE A 300 43.413 49.442 181.101 1.00 43.46 8
ATOM 467 N TYR A 301 42.633 49.235 183.187 1.00 43.37 7
ATOM 468 CA TYR A 301 41.429 49.921 182.832 1.00 43.36 6
ATOM 469 CB TYR A 301 40.294 49.605 183.797 1.00 44.03 6
ATOM 470 CG TYR A 301 39.635 48.296 183.445 1.00 44.73 6
ATOM 471 CDl TYR A 301 39.703 il .215 184.305 1.00 45.52 6
ATOM 472 CEI TYR A 301 39.114 46.008 183.972 1.00 45.74 6
ATOM 473 CZ TYR A 301 38.447 45.881 182.770 1.00 44.85 6
ATOM 474 OH TYR A 301 37.862 44.679 182.448 1.00 46.21 8
ATOM 475 CE2 TYR A 301 38.371 46.940 181.897 1.00 44.17 6
ATOM 476 CD2 TYR A 301 38.969 48.132 182.231 1.00 44.51 6
ATOM 477 C TYR A 301 41.624 51.407 182.613 1.00 43.09 6
ATOM 478 0 TYR A 301 40.897 52.007 181.821 1.00 43.38 8
ATOM 479 N LYS A 302 42.605 52.005 183.288 1.00 42.67 7
ATOM 480 CA LYS A 302 42.876 53.431 183.103 1.00 42.29 6
ATOM 481 CB LYS A 302 43.945 53.925 184.072 1.00 42.22 6
ATOM 482 CG LYS A 302 44.489 55.314 183.734 1.00 42.82 6
ATOM 483 CD LYS A 302 45.316 55.917 184.877 1.00 43.24 6
ATOM 484 CE LYS A 302 46.152 57.089 184.385 1.00 44.85 6
ATOM 485 NZ LYS A 302 47.558 56.891 184.885 1.00 48.09 7
ATOM 486 C LYS A 302 43.334 53.617 181.681 1.00 41.91 6
ATOM 487 0 LYS A 302 42.781 54.420 180.942 1.00 41.83 8 ATOM 488 N ALA A 303 44.333 52.824 181.305 1.00 41.91 7
ATOM 489 CA ALA A 303 44.837 52.743 179.936 1.00 41.67 6
ATOM 490 CB ALA A 303 45.889 51.676 179.868 1.00 41.61 6
ATOM 491 C ALA A 303 43.751 52.471 178.899 1.00 41.57 6
ATOM 492 O ALA A 303 43.739 53.068 177.844 1.00 41.66 8
ATOM 493 N ASP A 304 42.837 51.565 179.193 1.00 41.57 7
ATOM 494 CA ASP A 304 41.826 51.291 178.219 1.00 41.67 6
ATOM 495 CB ASP A 304 41.199 49.939 178.433 1.00 42.26 6
ATOM 496 CG ASP A 304 42.108 48.865 177.906 1.00 45.50 6
ATOM 497 ODl ASP A 304 42.244 47.797 178.547 1.00 49.37 8
ATOM 498 0D2 ASP A 304 42.750 49.136 176.853 1.00 46.89 8
ATOM 499 C ASP A 304 40.873 52.432 178.017 1.00 41.00 6
ATOM 500 O ASP A 304 40.549 52.755 176.862 1.00 41.04 8
ATOM 501 N PHE A 305 40.495 53.075 179.122 1.00 40.10 7
ATOM 502 CA PHE A 305 39.622 54.214 179.052 1.00 39.38 6
ATOM 503 CB PHE A 305 39.447 54.895 180.390 1.00 39.47 6
ATOM 504 CG PHE A 305 38.999 56.324 180.248 1.00 38.56 6
ATOM 505 CDl PHE A 305 37.680 56.622 180.002 1.00 38.06 6
ATOM 506 CEI PHE A 305 37.270 57.929 179.827 1.00 38.38 6
ATOM 507 CZ PHE A 305 38.170 58.944 179.885 1.00 38.12 6
ATOM 508 CE2 PHE A 305 39.493 58.657 180.120 1.00 39.16 6
ATOM 509 CD2 PHE A 305 39.905 57.352 180.291 1.00 38.01 6
ATOM 510 C PHE A 305 40.248 55.237 178.159 1.00 39.02 6
ATOM 511 O PHE A 305 39.594 55.830 177.305 1.00 38.98 8
ATOM 512 N GLN A 306 41.520 55.480 178.401 1.00 38.74 7
ATOM 513 CA GLN A 306 42.207 56.532 177.690 1.00 38.96 6
ATOM 514 CB GLN A 306 43.647 56.653 178.128 1.00 38.80 6
ATOM 515 CG GLN A 306 43.808 57.295 179.486 1.00 40.68 6
ATOM 516 CD GLN A 306 45.244 57.251 179.955 1.00 43.90 6
ATOM 517 OEl GLN A 306 46.159 57.403 179.154 1.00 45.50 8
ATOM 518 NE2 GLN A 306 45.456 57.029 181.254 1.00 45.70 7
ATOM 519 C GLN A 306 42.147 56.285 176.211 1.00 38.86 6
ATOM 520 0 GLN A 306 41.795 57.175 175.470 1.00 39.31 8
ATOM 521 N ALA A 307 42.457 55.069 175.774 1.00 38.67 7
ATOM 522 CA ALA A 307 42.296 54.738 174.367 1.00 38.13 6
ATOM 523 CB ALA A 307 42.852 53.400 174.054 1.00 37.84 6
ATOM 524 C ALA A 307 40.834 54.861 173.913 1.00 38.20 6
ATOM 525 O ALA A 307 40.600 55.327 172.808 1.00 38.71 8
ATOM 526 N GLU A 308 39.860 54.470 174.742 1.00 37.63 7
ATOM 527 CA GLU A 308 38.456 54.663 174.376 1.00 37.05 6
ATOM 528 CB GLU A 308 37.505 54.126 175.464 1.00 37.71 6
ATOM 529 CG GLU A 308 36.247 53.502 174.901 1.00 36.69 6
ATOM 530 CD GLU A 308 36.633 52.608 173.796 1.00 35.01 6
ATOM 531 OEl GLU A 308 35.850 52.419 172.842 1.00 34.91 8
ATOM 532 0E2 GLU A 308 37.777 52.128 173.897 1.00 34.26 8
ATOM 533 C GLU A 308 38.182 56.135 174.125 1.00 36.47 6
ATOM 534 O GLU A 308 37.667 56.522 173.062 1.00 36.25 8
ATOM 535 N ARG A 309 38.533 56.952 175.107 1.00 35.84 7
ATOM 536 CA ARG A 309 38.212 58.365 175.015 1.00 35.72 6
ATOM 537 CB ARG A 309 38.801 59.178 176.162 1.00 35.31 6
ATOM 538 CG ARG A 309 38.879 60.625 175.800 1.00 34.37 6
ATOM 539 CD ARG A 309 37.524 61.212 175.696 1.00 35.10 6
ATOM 540 NE ARG A 309 37.040 61.643 177.005 1.00 39.10 7
ATOM 541 CZ ARG A 309 35.860 61.296 177.521 1.00 40.41 6
ATOM 542 NHl ARG A 309 35.031 60.519 176.817 1.00 40.79 7
ATOM 543 NH2 ARG A 309 35.493 61.755 178.718 1.00 39.97 7 ATOM 544 C ARG A 309 38.756 58.894 173.712 1.00 35.44 6
ATOM 545 0 ARG A 309 38.082 59.644 172.999 1.00 35.73 8
ATOM 546 N HIS A 310 39.971 58.465 173.403 1.00 34.76 7
ATOM 547 CA HIS A 310 40.661 58.966 172.248 1.00 34.42 6
ATOM 548 CB HIS A 310 42.085 58.458 172.211 1.00 34.33 6
ATOM 549 CG HIS A 310 42.923 59.088 171.147 1.00 35.33 6
ATOM 550 NDl HIS A 310 42.587 59.041 169.809 1.00 36.33 7
ATOM 551 CEI HIS A 310 43.518 59.662 169.104 1.00 37.03 6
ATOM 552 NE2 HIS A 310 44.440 60.117 169.933 1.00 35.51 7
ATOM 553 CD2 HIS A 310 44.100 59.759 171.216 1.00 35.85 6
ATOM 554 C HIS A 310 39.906 58.654 170.954 1.00 34.42 6
ATOM 555 0 HIS A 310 39.729 59.561 170.136 1.00 35.07 8
ATOM 556 N ALA A 311 39.432 57.414 170.782 1.00 33.53 7
ATOM 557 CA ALA A 311 38.597 57.062 169.643 1.00 32.97 6
ATOM 558 CB ALA A 311 38.331 55.635 169.638 1.00 32.83 6
ATOM 559 C ALA A 311 37.292 57.807 169.700 1.00 33.26 6
ATOM 560 0 ALA A 311 36.860 58.387 168.692 1.00 33.19 8
ATOM 561 N ARG A 312 36.681 57.797 170.890 1.00 33.54 7
ATOM 562 CA ARG A 312 35.368 58.419 171.118 1.00 34.12 6
ATOM 563 CB ARG A 312 34.981 58.332 172.602 1.00 34.08 6
ATOM 564 CG ARG A 312 33.564 58.795 172.904 1.00 33.75 6
ATOM 565 CD ARG A 312 33.568 60.168 173.500 1.00 33.44 6
ATOM 566 NE ARG A 312 32.214 60.649 173.768 1.00 34.06 7
ATOM 567 CZ ARG A 312 31.479 60.316 174.835 1.00 34.22 6
ATOM 568 NHl ARG A 312 31.930 59.466 175.750 1.00 32.76 7
ATOM 569 NH2 ARG A 312 30.275 60.842 174.994 1.00 34.29 7
ATOM 570 C ARG A 312 35.325 59.869 170.605 1.00 34.42 6
ATOM 571 0 ARG A 312 34.316 60.315 170.048 1.00 34.07 8
ATOM 572 N GLU A 313 36.428 60.587 170.773 1.00 34.75 7
ATOM 573 CA GLU A 313 36.458 61.946 170.296 1.00 36.02 6
ATOM 574 CB GLU A 313 37.708 62.689 170.745 1.00 36.55 6
ATOM 575 CG GLU A 313 38.049 62.452 172.178 1.00 41.53 6
ATOM 576 CD GLU A 313 38.736 63.633 172.852 1.00 47.48 6
ATOM 577 OEl GLU A 313 39.548 64.319 172.183 1.00 49.77 8
ATOM 578 0E2 GLU A 313 38.474 63.861 174.071 1.00 51.50 8
ATOM 579 C GLU A 313 36.424 61.916 168.793 1.00 35.81 6
ATOM 580 0 GLU A 313 35.544 62.535 168.171 1.00 35.63 8
ATOM 581 N LYS A 314 37.380 61.174 168.221 1.00 35.72 7
ATOM 582 CA LYS A 314 37.626 61.218 166.791 1.00 35.35 6
ATOM 583 CB LYS A 314 38.691 60.223 166.382 1.00 34.98 6
ATOM 584 CG LYS A 314 40.087 60.772 166.447 1.00 35.33 6
ATOM 585 CD LYS A 314 41.051 59.859 165.734 1.00 35.09 6
ATOM 586 CE LYS A 314 42.340 60.551 165.370 1.00 35.42 6
ATOM 587 NZ LYS A 314 43.481 59.603 165.698 1.00 36.91 7
ATOM 588 C LYS A 314 36.338 60.933 166.078 1.00 35.71 6
ATOM 589 0 LYS A 314 36.074 61.546 165.043 1.00 35.61 8
ATOM 590 N LEU A 315 35.538 60.024 166.652 1.00 35.83 7
ATOM 591 CA LEU A 315 34.207 59.738 166.161 1.00 35.96 6
ATOM 592 CB LEU A 315 33.654 58.519 166.852 1.00 36.23 6
ATOM 593 CG LEU A 315 34.464 57.235 166.666 1.00 37.28 6
ATOM 594 CDl LEU A 315 34.300 56.299 167.872 1.00 37.09 6
ATOM 595 CD2 LEU A 315 34.081 56.519 165.369 1.00 37.93 6
ATOM 596 C LEU A 315 33.276 60.922 166.367 1.00 36.22 6
ATOM 597 0 LEU A 315 32.689 61.383 165.410 1.00 36.53 8
ATOM 598 N VAL A 316 33.152 61.440 167.590 1.00 36.39 7
ATOM 599 CA VAL A 316 32.242 62.560 167.843 1.00 36.51 6 ATOM 600 CB VAL A 316 32.494 63.210 169.210 1.00 36.14 6
ATOM 601 CGl VAL A 316 32.214 64.703 169.188 1.00 35.15 6
ATOM 602 CG2 VAL A 316 31.643 62.527 170.256 1.00 36.40 6
ATOM 603 C VAL A 316 32.452 63.557 166.752 1.00 37.11 6
ATOM 604 O VAL A 316 31.520 64.093 166.179 1.00 37.40 8
ATOM 605 N GLU A 317 33.717 63.740 166.447 1.00 38.09 7
ATOM 606 CA GLU A 317 34.185 64.668 165.461 1.00 39.29 6
ATOM 607 CB GLU A 317 35.701 64.645 165.561 1.00 39.91 6
ATOM 608 CG GLU A 317 36.455 64.939 164.313 1.00 43.05 6
ATOM 609 CD GLU A 317 36.686 66.421 164.139 1.00 46.07 6
ATOM 610 OEl GLU A 317 35.764 67.099 163.611 1.00 46.37 8
ATOM 611 0E2 GLU A 317 37.801 66.882 164.525 1.00 46.81 8
ATOM 612 C GLU A 317 33.683 64.266 164.069 1.00 39.27 6
ATOM 613 0 GLU A 317 33.067 65.057 163.375 1.00 39.27 8
ATOM 614 N LYS A 318 33.926 63.030 163.666 1.00 39.74 7
ATOM 615 CA LYS A 318 33.427 62.545 162.388 1.00 40.01 6
ATOM 616 CB LYS A 318 33.807 61.075 162.176 1.00 39.78 6
ATOM 617 CG LYS A 318 33.545 60.518 160.781 1.00 38.10 6
ATOM 618 CD LYS A 318 34.142 61.396 159.706 1.00 37.70 6
ATOM 619 CE LYS A 318 35.618 61.160 159.463 1.00 36.88 6
ATOM 620 NZ LYS A 318 36.080 62.044 158.344 1.00 36.59 7
ATOM 621 C LYS A 318 31.911 62.738 162.300 1.00 40.85 6
ATOM 622 0 LYS A 318 31.436 63.299 161.316 1.00 41.51 8
ATOM 623 N LYS A 319 31.156 62.300 163.317 1.00 41.24 7
ATOM 624 CA LYS A 319 29.701 62.528 163.347 1.00 41.73 6
ATOM 625 CB LYS A 319 29.084 62.138 164.697 1.00 41.47 6
ATOM 626 CG LYS A 319 27.567 62.314 164.735 1.00 43.40 6
ATOM 627 CD LYS A 319 27.032 62.547 166.157 1.00 46.30 6
ATOM 628 CE LYS A 319 27.301 63.987 166.703 1.00 48.83 6
ATOM 629 NZ LYS A 319 27.319 64.156 168.232 1.00 47.00 7
ATOM 630 C LYS A 319 29.357 63.989 162.968 1.00 41.84 6
ATOM 631 O LYS A 319 28.618 64.212 161.998 1.00 41.46 8
ATOM 632 N GLU A 320 29.918 64.954 163.708 1.00 42.07 7
ATOM 633 CA GLU A 320 29.738 66.378 163.420 1.00 43.11 6
ATOM 634 CB GLU A 320 30.742 67.278 164.178 1.00 43.58 6
ATOM 635 CG GLU A 320 30.704 67.236 165.711 1.00 47.05 6
ATOM 636 CD GLU A 320 29.305 67.499 166.296 1.00 52.10 6
ATOM 637 OEl GLU A 320 28.575 68.364 165.725 1.00 53.88 8
ATOM 638 0E2 GLU A 320 28.941 66.846 167.327 1.00 52.67 8
ATOM 639 C GLU A 320 29.917 66.625 161.934 1.00 43.15 6
ATOM 640 O GLU A 320 29.005 67.145 161.273 1.00 43.42 8
ATOM 641 N TYR A 321 31.095 66.254 161.419 1.00 42.94 7
ATOM 642 CA TYR A 321 31.440 66.468 160.019 1.00 42.74 6
ATOM 643 CB TYR A 321 32.822 65.892 159.681 1.00 42.84 6
ATOM 644 CG TYR A 321 33.110 65.974 158.209 1.00 42.31 6
ATOM 645 CDl TYR A 321 33.494 67.171 157.626 1.00 42.85 6
ATOM 646 CEI TYR A 321 33.722 67.265 156.258 1.00 42.57 6
ATOM 647 CZ TYR A 321 33.549 66.155 155.474 1.00 42.11 6
ATOM 648 OH TYR A 321 33.768 66.233 154.135 1.00 41.62 8
ATOM 649 CE2 TYR A 321 33.155 64.959 156.030 1.00 42.63 6
ATOM 650 CD2 TYR A 321 32.940 64.875 157.393 1.00 42.41 6
ATOM 651 C TYR A 321 30.386 65.887 159.077 1.00 43.07 6
ATOM 652 0 TYR A 321 30.001 66.540 158.100 1.00 43.16 8
ATOM 653 N LEU A 322 29.908 64.678 159.372 1.00 43.28 7
ATOM 654 CA LEU A 322 28.896 64.066 158.533 1.00 43.76 6
ATOM 655 CB LEU A 322 28.746 62.609 158.866 1.00 43.15 6 ATOM 656 CG LEU A 322 29.982 61.842 158.414 1.00 42.73 6
ATOM 657 CDl LEU A 322 29.634 60.383 158.329 1.00 43.70 6
ATOM 658 CD2 LEU A 322 30.511 62.294 157.067 1.00 41.08 6
ATOM 659 C LEU A 322 27.558 64.796 158.570 1.00 44.89 6
ATOM 660 0 LEU A 322 26.940 64.986 157.521 1.00 44.77 8
ATOM 661 N GLN A 323 27.130 65.222 159.765 1.00 46.29 7
ATOM 662 CA GLN A 323 25.897 65.992 159.923 1.00 47.61 6
ATOM 663 CB GLN A 323 25.660 66.385 161.389 1.00 47.12 6
ATOM 664 CG GLN A 323 24.868 65.349 162.230 1.00 48.21 6
ATOM 665 CD GLN A 323 25.298 65.253 163.746 1.00 49.49 6
ATOM 666 OEl GLN A 323 26.009 66.118 164.271 1.00 52.44 8
ATOM 667 NE2 GLN A 323 24.853 64.191 164.432 1.00 50.57 7
ATOM 668 C GLN A 323 25.936 67.198 158.991 1.00 48.24 6
ATOM 669 O GLN A 323 24.972 67.450 158.280 1.00 48.14 8
ATOM 670 N GLU A 324 27.069 67.898 158.954 1.00 49.58 7
ATOM 671 CA GLU A 324 27.248 69.031 158.049 1.00 51.32 6
ATOM 672 CB GLU A 324 28.576 69.727 158.274 1.00 51.84 6
ATOM 673 CG GLU A 324 28.583 70.635 159.464 1.00 55.85 6
ATOM 674 CD GLU A 324 29.959 70.704 160.124 1.00 61.05 6
ATOM 675 OEl GLU A 324 30.982 70.661 159.377 1.00 63.21 8
ATOM 676 OE2 GLU A 324 30.007 70.808 161.383 1.00 62.05 8
ATOM 677 C GLU A 324 27.164 68.619 156.602 1.00 51.58 6
ATOM 678 0 GLU A 324 26.410 69.208 155.839 1.00 51.72 8
ATOM 679 N GLN A 325 27.934 67.617 156.213 1.00 52.30 7
ATOM 680 CA GLN A 325 27.848 67.141 154.853 1.00 53.55 6
ATOM 681 CB GLN A 325 28.648 65.869 154.678 1.00 53.62 6
ATOM 682 CG GLN A 325 30.135 66.083 154.783 1.00 54.69 6
ATOM 683 CD GLN A 325 30.610 67.299 154.022 1.00 55.31 6
ATOM 684 OEl GLN A 325 30.791 68.372 154.600 1.00 56.28 8
ATOM 685 NE2 GLN A 325 30.812 67.142 152.718 1.00 55.13 7
ATOM 686 C GLN A 325 26.408 66.886 154.450 1.00 54.36 6
ATOM 687 O GLN A 325 25.992 67.266 153.364 1.00 54.56 8
ATOM 688 N LEU A 326 25.651 66.242 155.334 1.00 55.40 7
ATOM 689 CA LEU A 326 24.231 66.011 155.116 1.00 56.16 6
ATOM 690 CB LEU A 326 23.655 65.054 156.158 1.00 55.64 6
ATOM 691 CG LEU A 326 23.334 63.651 155.640 1.00 54.81 6
ATOM 692 CDl LEU A 326 22.347 62.962 156.519 1.00 54.72 6
ATOM 693 CD2 LEU A 326 22.741 63.728 154.275 1.00 55.41 6
ATOM 694 C LEU A 326 23.394 67.280 155.046 1.00 57.27 6
ATOM 695 0 LEU A 326 22.473 67.352 154.250 1.00 57.66 8
ATOM 696 N GLU A 327 23.700 68.274 155.867 1.00 58.54 7
ATOM 697 CA GLU A 327 22.969 69.523 155.786 1.00 60.05 6
ATOM 698 CB GLU A 327 23.312 70.445 156.960 1.00 60.19 6
ATOM 699 CG GLU A 327 22.394 71.676 157.155 1.00 61.03 6
ATOM 700 CD GLU A 327 20.925 71.335 157.421 1.00 62.03 6
ATOM 701 OEl GLU A 327 20.573 70.136 157.386 1.00 62.52 8
ATOM 702 0E2 GLU A 327 20.119 72.271 157.654 1.00 61.96 8
ATOM 703 C GLU A 327 23.223 70.171 154.430 1.00 61.19 6
ATOM 704 0 GLU A 327 22.296 70.280 153.630 1.00 61.54 8
ATOM 705 N GLN A 328 24.471 70.552 154.162 1.00 62.53 7
ATOM 706 CA GLN A 328 24.859 71.117 152.872 1.00 64.22 6
ATOM 707 CB GLN A 328 26.376 71.194 152.765 1.00 64.79 6
ATOM 708 CG GLN A 328 26.920 72.612 152.670 1.00 67.70 6
ATOM 709 CD GLN A 328 26.291 73.586 153.686 1.00 71.01 6
ATOM 710 OEl GLN A 328 26.909 73.906 154.721 1.00 71.92 8
ATOM 711 NE2 GLN A 328 25.070 74.074 153.384 1.00 70.50 7 ATOM 712 C GLN A 328 24.301 70.399 151.657 1.00 64.82 6
ATOM 713 O GLN A 328 23.890 71.048 150.701 1.00 65.09 8
ATOM 714 N LEU A 329 24.284 69.070 151.697 1.00 65.64 7
ATOM 715 CA LEU A 329 23.826 68.287 150.570 1.00 66.69 6
ATOM 716 CB LEU A 329 24.313 66.850 150.673 1.00 66.65 6
ATOM 717 CG LEU A 329 24.342 66.023 149.383 1.00 66.07 6
ATOM 718 CDl LEU A 329 23.112 65.170 149.269 1.00 64.76 6
ATOM 719 CD2 LEU A 329 24.538 66.908 148.133 1.00 65.81 6
ATOM 720 C LEU A 329 22.329 68.297 150.460 1.00 67.81 6
ATOM 721 O LEU A 329 21.803 68.298 149.367 1.00 68.11 8
ATOM 722 N GLN A 330 21.645 68.290 151.593 1.00 69.44 7
ATOM 723 CA GLN A 330 20.188 68.357 151.614 1.00 71.03 6
ATOM 724 CB GLN A 330 19.679 67.995 153.017 1.00 71.12 6
ATOM 725 CG GLN A 330 18.174 68.148 153.273 1.00 72.41 6
ATOM 726 CD GLN A 330 17.288 67.401 152.272 1.00 74.23 6
ATOM 727 OEl GLN A 330 17.731 66.458 151.605 1.00 74.44 8
ATOM 728 NE2 GLN A 330 16.023 67.828 152.166 1.00 74.54 7
ATOM 729 C GLN A 330 19.662 69.726 151.149 1.00 71.91 6
ATOM 730 O GLN A 330 18.555 69.841 150.611 1.00 71.92 8
ATOM 731 N ARG A 331 20.470 70.759 151.338 1.00 73.14 7
ATOM 732 CA ARG A 331 20.103 72.086 150.868 1.00 74.41 6
ATOM 733 CB ARG A 331 20.850 73.164 151.648 1.00 74.06 6
ATOM 734 CG ARG A 331 20.530 73.166 153.130 1.00 72.82 6
ATOM 735 CD ARG A 331 21.195 74.320 153.847 1.00 70.75 6
ATOM 736 NE ARG A 331 20.934 74.285 155.281 1.00 68.50 7
ATOM 737 CZ ARG A 331 21.401 75.171 156.148 1.00 67.16 6
ATOM 738 NHl ARG A 331 22.158 76.175 155.740 1.00 66.73 7
ATOM 739 NH2 ARG A 331 21.110 75.046 157.425 1.00 66.80 7
ATOM 740 C ARG A 331 20.290 72.244 149.353 1.00 75.79 6
ATOM 741 0 ARG A 331 19.729 73.163 148.747 1.00 76.06 8
ATOM 742 N GLU A 332 21.065 71.341 148.756 1.00 77.29 7
ATOM 743 CA GLU A 332 21.313 71.315 147.315 1.00 78.99 6
ATOM 744 CB GLU A 332 22.620 70.585 147.039 1.00 79.10 6
ATOM 745 CG GLU A 332 23.711 71.450 146.478 1.00 80.61 6
ATOM 746 CD GLU A 332 23.989 72.646 147.343 1.00 82.74 6
ATOM 747 OEl GLU A 332 24.867 72.518 148.227 1.00 83.96 8
ATOM 748 0E2 GLU A 332 23.320 73.696 147.151 1.00 83.56 8
ATOM 749 C GLU A 332 20.204 70.606 146.571 1.00 79.91 6
ATOM 750 0 GLU A 332 19.723 71.079 145.544 1.00 80.08 8
ATOM 751 N PHE A 333 19.844 69.444 147.101 1.00 81.18 7
ATOM 752 CA PHE A 333 18.723 68.641 146.664 1.00 82.48 6
ATOM 753 CB PHE A 333 18.650 67.409 147.570 1.00 82.54 6
ATOM 754 CG PHE A 333 17.756 66.304 147.064 1.00 83.09 6
ATOM 755 CDl PHE A 333 18.246 65.346 146.166 1.00 83.45 6
ATOM 756 CEI PHE A 333 17.415 64.305 145.706 1.00 83.73 6
ATOM 757 CZ PHE A 333 16.090 64.210 146.163 1.00 83.17 6
ATOM 758 CE2 PHE A 333 15.599 65.154 147.070 1.00 83.22 6
ATOM 759 CD2 PHE A 333 16.435 66.188 147.524 1.00 83.25 6
ATOM 760 C PHE A 333 17.437 69.442 146.807 1.00 83.43 6
ATOM 761 0 PHE A 333 16.386 69.032 146.321 1.00 83.77 8
ATOM 762 N ASN A 334 17.501 70.581 147.488 1.00 84.40 7
ATOM 763 CA ASN A 334 16.296 71.386 147.639 1.00 85.15 6
ATOM 764 CB ASN A 334 15.912 71.564 149.109 1.00 85.01 6
ATOM 765 CG ASN A 334 15.577 70.238 149.789 1.00 84.20 6
ATOM 766 ODl ASN A 334 15.334 69.226 149.129 1.00 82.90 8
ATOM 767 ND2 ASN A 334 15.566 70.244 151.113 1.00 83.01 7 ATOM 768 C ASN A 334 16.271 72.685 146.851 1.00 85.96 6
ATOM 769 0 ASN A 334 15.203 13.111 146.533 1.00 86.07 8
ATOM 770 N LYS A 335 17.433 73.227 146.514 1.00 87.13 7
ATOM 771 CA LYS A 335 17.478 74.371 145.609 1.00 88.32 6
ATOM 772 CB LYS A 335 18.704 75.249 145.885 1.00 88.31 6
ATOM 773 CG LYS A 335 18.469 76.248 147.008 1.00 88.61 6
ATOM 774 CD LYS A 335 19.747 76.581 147.736 1.00 89.01 6
ATOM 775 CE LYS A 335 19.443 77.262 149.053 1.00 88.95 6
ATOM 776 NZ LYS A 335 20.688 77.591 149.787 1.00 89.07 7
ATOM 777 C LYS A 335 17.393 73.904 144.152 1.00 89.02 6
ATOM 778 0 LYS A 335 16.719 74.527 143.331 1.00 89.20 8
ATOM 779 N LEU A 336 18.056 72.784 143.866 1.00 89.96 7
ATOM 780 CA LEU A 336 18.036 72.115 142.561 1.00 90.64 6
ATOM 781 CB LEU A 336 19.400 71.409 142.351 1.00 90.53 6
ATOM 782 CG LEU A 336 19.972 70.837 141.042 1.00 90.21 6
ATOM 783 CDl LEU A 336 21.423 71.285 140.821 1.00 89.63 6
ATOM 784 CD2 LEU A 336 19.876 69.315 141.019 1.00 89.73 6
ATOM 785 C LEU A 336 16.859 71.116 142.514 1.00 91.24 6
ATOM 786 0 LEU A 336 16.832 70.217 141.674 1.00 91.39 8
ATOM 787 N LYS A 337 15.882 71.300 143.409 1.00 91.82 7
ATOM 788 CA LYS A 337 14.740 70.380 143.547 1.00 92.31 6
ATOM 789 CB LYS A 337 14.005 70.624 144.869 1.00 92.40 6
ATOM 790 CG LYS A 337 13.216 69.416 145.375 1.00 92.55 6
ATOM 791 CD LYS A 337 12.668 69.637 146.776 1.00 92.33 6
ATOM 792 CE LYS A 337 12.199 68.330 147.383 1.00 91.45 6
ATOM 793 NZ LYS A 337 11.469 68.579 148.642 1.00 90.92 7
ATOM 794 C LYS A 337 13.747 70.442 142.382 1.00 92.61 6
ATOM 795 0 LYS A 337 14.096 70.638 141.218 1.00 92.91 8
ATOM 796 OXT LYS A 337 12.530 70.339 142.576 1.00 92.65 8
ATOM 797 N SER B 247 74.573 13.366 243.691 1.00 80.34 7
ATOM 798 CA SER B 247 74.309 12.439 244.839 1.00 80.35 6
ATOM 799 CB SER B 247 75.563 12.231 245.702 1.00 80.24 6
ATOM 800 OG SER B 247 75.643 13.191 246.747 1.00 79.88 8
ATOM 801 C SER B 247 73.158 12.935 245.711 1.00 80.47 6
ATOM 802 0 SER B 247 73.052 14.136 246.002 1.00 80.69 8
ATOM 803 N MET B 248 72.305 11.990 246.111 1.00 80.37 7
ATOM 804 CA MET B 248 71.164 12.223 247.014 1.00 80.13 6
ATOM 805 CB MET B 248 71.640 12.350 248.464 1.00 80.27 6
ATOM 806 CG MET B 248 71.518 11.068 249.289 1.00 79.98 6
ATOM 807 SD MET B 248 70.989 11.478 250.975 1.00 80.26 16
ATOM 808 CE MET B 248 69.329 12.195 250.686 1.00 79.56 6
ATOM 809 C MET B 248 70.196 13.367 246.647 1.00 79.85 6
ATOM 810 0 MET B 248 69.780 13.496 245.490 1.00 79.97 8
ATOM 811 N ALA B 249 69.858 14.198 247.634 1.00 79.47 7
ATOM 812 CA ALA B 249 68.688 15.087 247.548 1.00 79.06 6
ATOM 813 CB ALA B 249 67.809 14.918 248.822 1.00 79.23 6
ATOM 814 C ALA B 249 68.910 16.590 247.213 1.00 78.53 6
ATOM 815 0 ALA B 249 67.932 17.336 247.113 1.00 78.39 8
ATOM 816 N SER B 250 70.165 17.029 247.043 1.00 77.83 7
ATOM 817 CA SER B 250 70.461 18.421 246.613 1.00 76.92 6
ATOM 818 CB SER B 250 71.441 19.134 247.556 1.00 76.81 6
ATOM 819 OG SER B 250 72.159 20.157 246.883 1.00 76.19 8
ATOM 820 C SER B 250 70.957 18.537 245.174 1.00 76.35 6
ATOM 821 0 SER B 250 70.929 19.630 244.602 1.00 76.22 8
ATOM 822 N MET B 251 71.423 17.429 244.598 1.00 75.47 7
ATOM 823 CA MET B 251 71.623 17.393 243.156 1.00 74.63 6 ATOM 824 CB MET B 251 72.286 16.088 242.700 1.00 74.73 6
ATOM 825 CG MET B 251 73.773 16.275 242.344 1.00 74.68 6
ATOM 826 SD MET B 251 74.208 16.478 240.572 1.00 75.60 16
ATOM 827 CE MET B 251 73.183 17.815 239.951 1.00 73.52 6
ATOM 828 C MET B 251 70.290 17.711 242.440 1.00 74.03 6
ATOM 829 0 MET B 251 70.286 18.172 241.298 1.00 74.00 8
ATOM 830 N GLN B 252 69.182 17.451 243.144 1.00 72.87 7
ATOM 831 CA GLN B 252 67.851 18.069 242.946 1.00 72.59 6
ATOM 832 CB GLN B 252 66.945 17.790 244.146 1.00 72.33 6
ATOM 833 CG GLN B 252 66.634 16.334 244.398 1.00 71.53 6
ATOM 834 CD GLN B 252 65.387 16.169 245.230 1.00 70.50 6
ATOM 835 OEl GLN B 252 65.461 15.858 246.419 1.00 70.46 8
ATOM 836 NE2 GLN B 252 64.230 16.399 244.617 1.00 69.54 7
ATOM 837 C GLN B 252 67.846 19.584 242.725 1.00 72.68 6
ATOM 838 0 GLN B 252 66.989 20.109 242.008 1.00 72.59 8
ATOM 839 N LEU B 253 68.769 20.300 243.357 1.00 72.96 7
ATOM 840 CA LEU B 253 68.833 21.736 243.122 1.00 73.18 6
ATOM 841 CB LEU B 253 69.477 22.490 244.297 1.00 72.92 6
ATOM 842 CG LEU B 253 69.411 24.021 244.327 1.00 72.11 6
ATOM 843 CDl LEU B 253 69.199 24.559 245.739 1.00 70.21 6
ATOM 844 CD2 LEU B 253 70.667 24.610 243.715 1.00 71.43 6
ATOM 845 C LEU B 253 69.435 22.076 241.748 1.00 73.75 6
ATOM 846 0 LEU B 253 69.037 23.068 241.143 1.00 73.75 8
ATOM 847 N GLU B 254 70.343 21.245 241.233 1.00 74.41 7
ATOM 848 CA GLU B 254 70.856 21.493 239.886 1.00 75.13 6
ATOM 849 CB GLU B 254 72.220 20.839 239.614 1.00 75.29 6
ATOM 850 CG GLU B 254 73.358 21.765 240.031 1.00 75.77 6
ATOM 851 CD GLU B 254 72.914 23.240 240.063 1.00 76.49 6
ATOM 852 OEl GLU B 254 72.725 23.833 238.973 1.00 76.50 8
ATOM 853 0E2 GLU B 254 72.734 23.792 241.178 1.00 76.16 8
ATOM 854 C GLU B 254 69.831 21.299 238.772 1.00 75.31 6
ATOM 855 0 GLU B 254 69.895 21.981 237.748 1.00 75.32 8
ATOM 856 N ASP B 255 68.885 20.383 238.997 1.00 75.53 7
ATOM 857 CA ASP B 255 67.747 20.205 238.102 1.00 75.89 6
ATOM 858 CB ASP B 255 66.728 19.206 238.669 1.00 76.17 6
ATOM 859 CG ASP B 255 67.374 17.947 239.232 1.00 77.38 6
ATOM 860 ODl ASP B 255 68.585 17.722 239.014 1.00 78.27 8
ATOM 861 0D2 ASP B 255 66.657 17.172 239.903 1.00 79.00 8
ATOM 862 C ASP B 255 67.093 21.565 237.994 1.00 75.80 6
ATOM 863 0 ASP B 255 67.115 22.198 236.924 1.00 75.90 8
ATOM 864 N LEU B 256 66.548 22.018 239.124 1.00 75.52 7
ATOM 865 CA LEU B 256 65.892 23.309 239.211 1.00 75.24 6
ATOM 866 CB LEU B 256 65.550 23.650 240.656 1.00 75.14 6
ATOM 867 CG LEU B 256 64.603 22.714 241.416 1.00 74.95 6
ATOM 868 CDl LEU B 256 64.035 23.460 242.596 1.00 74.46 6
ATOM 869 CD2 LEU B 256 63.468 22.170 240.559 1.00 74.53 6
ATOM 870 C LEU B 256 66.748 24.396 238.599 1.00 75.23 6
ATOM 871 0 LEU B 256 66.322 25.076 237.681 1.00 75.26 8
ATOM 872 N ARG B 257 67.973 24.539 239.061 1.00 75.41 7
ATOM 873 CA ARG B 257 68.760 25.623 238.529 1.00 75.72 6
ATOM 874 CB ARG B 257 70.006 25.859 239.344 1.00 75.90 6
ATOM 875 CG ARG B 257 69.671 26.588 240.622 1.00 76.28 6
ATOM 876 CD ARG B 257 69.917 28.087 240.509 1.00 76.40 6
ATOM 877 NE ARG B 257 69.597 28.787 241.757 1.00 77.53 7
ATOM 878 CZ ARG B 257 70.125 28.525 242.960 1.00 78.51 6
ATOM 879 NHl ARG B 257 71.016 27.554 243.140 1.00 78.70 7 ATOM 880 NH2 ARG B 257 69.748 29.240 244.009 1.00 79.07 7
ATOM 881 C ARG B 257 69.018 25.546 237.035 1.00 75.87 6
ATOM 882 0 ARG B 257 68.981 26.580 236.387 1.00 75.77 8
ATOM 883 N GLN B 258 69.226 24.341 236.491 1.00 76.21 7
ATOM 884 CA GLN B 258 69.279 24.149 235.032 1.00 76.55 6
ATOM 885 CB GLN B 258 69.742 22.740 234.622 1.00 76.74 6
ATOM 886 CG GLN B 258 71.192 22.662 234.152 1.00 77.32 6
ATOM 887 CD GLN B 258 72.182 23.127 235.215 1.00 78.99 6
ATOM 888 OEl GLN B 258 72.866 22.313 235.844 1.00 79.45
ATOM 889 NE2 GLN B 258 72.256 24.441 235.426 1.00 79.31 7
ATOM 890 C GLN B 258 67.951 24.481 234.399 1.00 76.49 6
ATOM 891 0 GLN B 258 67.871 25.437 233.641 1.00 76.75
ATOM 892 N GLN B 259 66.900 23.733 234.710 1.00 76.38
ATOM 893 CA GLN B 259 65.661 24.019 234.013 1.00 76.80
ATOM 894 CB GLN B 259 64.502 23.099 234.358 1.00 76.80 6
ATOM 895 CG GLN B 259 64.603 22.387 235.643 1.00 77.49 6
ATOM 896 CD GLN B 259 64.144 20.963 235.496 1.00 78.50 6
ATOM 897 OEl GLN B 259 63.675 20.564 234.430 1.00 78.56 8
ATOM 898 NE2 GLN B 259 64.283 20.178 236.558 1.00 79.70 7
ATOM 899 C GLN B 259 65.270 25.483 234.073 1.00 77.10 6
ATOM 900 O GLN B 259 64.696 25.989 233.107 1.00 77.35 8
ATOM 901 N LEU B 260 65.617 26.169 235.165 1.00 77.36 7
ATOM 902 CA LEU B 260 65.368 27.606 235.256 1.00 77.65 6
ATOM 903 CB LEU B 260 65.623 28.148 236.663 1.00 77.58 6
ATOM 904 CG LEU B 260 64.777 29.348 237.142 1.00 77.11 6
ATOM 905 CDl LEU B 260 65.500 30.693 236.998 1.00 76.64 6
ATOM 906 CD2 LEU B 260 63.393 29.398 236.498 1.00 75.83 6
ATOM 907 C LEU B 260 66.169 28.367 234.201 1.00 78.15 6
ATOM 908 O LEU B 260 65.588 29.072 233.384 1.00 78.37 8
ATOM 909 N GLN B 261 67.490 28.208 234.197 1.00 78.78 7
ATOM 910 CA GLN B 261 68.328 28.800 233.141 1.00 79.49 6
ATOM 911 CB GLN B 261 69.804 28.369 233.264 1.00 79.70 6
ATOM 912 CG GLN B 261 70.799 29.512 233.481 1.00 80.39 6
ATOM 913 CD GLN B 261 70.504 30.712 232.595 1.00 82.13 6
ATOM 914 OEl GLN B 261 70.458 30.602 231.365 1.00 82.63 8
ATOM 915 NE2 GLN B 261 70.285 31.865 233.219 1.00 82.64 7
ATOM 916 C GLN B 261 67.825 28.469 231.733 1.00 79.64 6
ATOM 917 0 GLN B 261 67.853 29.316 230.841 1.00 79.71
ATOM 918 N GLN B 262 67.376 27.231 231.552 1.00 79.89 7
ATOM 919 CA GLN B 262 66.880 26.748 230.275 1.00 80.36 6
ATOM 920 CB GLN B 262 66.504 25.279 230.382 1.00 80.40 6
ATOM 921 CG GLN B 262 67.649 24.319 230.179 1.00 81.23 6
ATOM 922 CD GLN B 262 67.227 23.099 229.385 1.00 82.18
ATOM 923 OEl GLN B 262 68.003 22.575 228.582 1.00 83.19
ATOM 924 NE2 GLN B 262 65.985 22.653 229.584 1.00 82.04 7
ATOM 925 C GLN B 262 65.649 27.493 229.841 1.00 80.42 6
ATOM 926 0 GLN B 262 65.508 27.861 228.680 1.00 80.53 8
ATOM 927 N ALA B 263 64.739 27.693 230.779 1.00 80.58 7
ATOM 928 CA ALA B 263 63.495 28.343 230.452 1.00 80.73 6
ATOM 929 CB ALA B 263 62.431 28.013 231.473 1.00 80.83
ATOM 930 C ALA B 263 63.668 29.853 230.256 1.00 80.96
ATOM 931 0 ALA B 263 63.103 30.401 229.309 1.00 81.15
ATOM 932 N GLU B 264 64.458 30.519 231.104 1.00 81.16 7
ATOM 933 CA GLU B 264 64.738 31.950 230.905 1.00 81.56 6
ATOM 934 CB GLU B 264 65.651 32.499 231.988 1.00 81.50 6
ATOM 935 CG GLU B 264 64.907 32.850 233.240 1.00 82.27 6 ATOM 936 CD GLU B 264 65.844 33.157 234.373 1.00 84.36 6
ATOM 937 OEl GLU B 264 65.624 34.178 235.058 1.00 85.59 8
ATOM 938 0E2 GLU B 264 66.815 32.387 234.574 1.00 85.60 8
ATOM 939 C GLU B 264 65.318 32.214 229.518 1.00 81.55 6
ATOM 940 0 GLU B 264 64.982 33.214 228.873 1.00 81.73 8
ATOM 941 N GLU B 265 66.164 31.286 229.072 1.00 81.47 7
ATOM 942 CA GLU B 265 66.745 31.253 227.733 1.00 81.30 6
ATOM 943 CB GLU B 265 67.619 30.008 227.641 1.00 81.19 6
ATOM 944 CG GLU B 265 68.933 30.177 226.937 1.00 81.44 6
ATOM 945 CD GLU B 265 69.964 29.190 227.446 1.00 81.63 6
ATOM 946 OEl GLU B 265 70.951 28.923 226.724 1.00 81.94 8
ATOM 947 0E2 GLU B 265 69.784 28.684 228.576 1.00 81.79 8
ATOM 948 C GLU B 265 65.672 31.172 226.645 1.00 81.05 6
ATOM 949 0 GLU B 265 65.693 31.936 225.677 1.00 81.10 8
ATOM 950 N ALA B 266 64.740 30.236 226.798 1.00 80.59 7
ATOM 951 CA ALA B 266 63.670 30.107 225.827 1.00 80.10 6
ATOM 952 CB ALA B 266 62.871 28.856 226.047 1.00 79.83 6
ATOM 953 C ALA B 266 62.791 31.346 225.858 1.00 79.95 6
ATOM 954 0 ALA B 266 62.359 31.820 224.822 1.00 80.15 8
ATOM 955 N LEU B 267 62.559 31.905 227.034 1.00 79.65 7
ATOM 956 CA LEU B 267 61.769 33.104 227.096 1.00 79.38 6
ATOM 957 CB LEU B 267 61.604 33.567 228.531 1.00 79.27 6
ATOM 958 CG LEU B 267 60.693 32.580 229.237 1.00 78.77 6
ATOM 959 CDl LEU B 267 60.468 33.027 230.675 1.00 79.02 6
ATOM 960 CD2 LEU B 267 59.390 32.454 228.464 1.00 78.39 6
ATOM 961 C LEU B 267 62.334 34.186 226.176 1.00 79.46 6
ATOM 962 0 LEU B 267 61.573 34.756 225.387 1.00 79.66 8
ATOM 963 N VAL B 268 63.648 34.447 226.234 1.00 79.24 7
ATOM 964 CA VAL B 268 64.234 35.479 225.356 1.00 79.03 6
ATOM 965 CB VAL B 268 65.708 35.851 225.658 1.00 78.76 6
ATOM 966 CGl VAL B 268 65.781 37.162 226.428 1.00 78.41 6
ATOM 967 CG2 VAL B 268 66.424 34.745 226.376 1.00 78.78 6
ATOM 968 C VAL B 268 64.090 35.084 223.897 1.00 79.12 6
ATOM 969 0 VAL B 268 63.742 35.919 223.060 1.00 79.24 8
ATOM 970 N ALA B 269 64.324 33.802 223.609 1.00 79.11 7
ATOM 971 CA ALA B 269 64.153 33.250 222.261 1.00 78.86 6
ATOM 972 CB ALA B 269 64.496 31.767 222.222 1.00 78.43 6
ATOM 973 C ALA B 269 62.756 33.490 221.711 1.00 78.81 6
ATOM 974 0 ALA B 269 62.607 33.865 220.566 1.00 79.01 8
ATOM 975 N LYS B 270 61.725 33.299 222.511 1.00 78.88 7
ATOM 976 CA LYS B 270 60.396 33.540 221.978 1.00 79.15 6
ATOM 977 CB LYS B 270 59.330 32.685 222.685 1.00 79.22 6
ATOM 978 CG LYS B 270 59.526 31.159 222.483 1.00 79.30 6
ATOM 979 CD LYS B 270 58.326 30.317 223.017 1.00 79.49 6
ATOM 980 CE LYS B 270 58.714 28.872 223.468 1.00 79.40 6
ATOM 981 NZ LYS B 270 59.273 27.914 222.441 1.00 78.19 7
ATOM 982 C LYS B 270 60.057 35.047 221.841 1.00 79.26 6
ATOM 983 0 LYS B 270 59.396 35.447 220.881 1.00 79.15 8
ATOM 984 N GLN B 271 60.554 35.881 222.751 1.00 79.44 7
ATOM 985 CA GLN B 271 60.407 37.320 222.590 1.00 79.74 6
ATOM 986 CB GLN B 271 60.929 38.075 223.801 1.00 79.76 6
ATOM 987 CG GLN B 271 60.070 39.272 224.114 1.00 80.42 6
ATOM 988 CD GLN B 271 58.629 38.865 224.375 1.00 81.53 6
ATOM 989 OEl GLN B 271 57.967 38.297 223.507 1.00 81.18 8
ATOM 990 NE2 GLN B 271 58.140 39.146 225.584 1.00 82.89 7
ATOM 991 C GLN B 271 61.069 37.830 221.304 1.00 79.93 6 ATOM 992 O GLN B 271 60.507 38.686 220.612 1.00 80.16 8
ATOM 993 N GLU B 272 62.248 37.291 220.989 1.00 79.88 7
ATOM 994 CA GLU B 272 62.933 37.560 219.725 1.00 79.76 6
ATOM 995 CB GLU B 272 64.115 36.603 219.560 1.00 80.02 6
ATOM 996 CG GLU B 272 65.454 37.266 219.247 1.00 81.01 6
ATOM 997 CD GLU B 272 66.625 36.636 220.020 1.00 82.17 6
ATOM 998 OEl GLU B 272 67.732 36.548 219.448 1.00 82.51 8
ATOM 999 OE2 GLU B 272 66.445 36.236 221.197 1.00 82.24 8
ATOM 1000 C GLU B 272 61.952 37.363 218.579 1.00 79.48 6
ATOM 1001 O GLU B 272 61.899 38.176 217.663 1.00 79.61 8
ATOM 1002 N LEU B 273 61.150 36.303 218.648 1.00 79.03 7
ATOM 1003 CA LEU B 273 60.191 36.028 217.588 1.00 78.54 6
ATOM 1004 CB LEU B 273 59.879 34.542 217.506 1.00 78.39 6
ATOM 1005 CG LEU B 273 59.663 34.064 216.076 1.00 77.93 6
ATOM 1006 CDl LEU B 273 60.995 34.032 215.347 1.00 77.93 ' 6
ATOM 1007 CD2 LEU B 273 59.007 32.695 216.056 1.00 77.26 6
ATOM 1008 C LEU B 273 58.914 36.858 217.685 1.00 78.45 6
ATOM 1009 O LEU B 273 58.353 37.242 216.676 1.00 78.45 8
ATOM 1010 N ILE B 274 58.457 37.139 218.893 1.00 78.25 7
ATOM 1011 CA ILE B 274 57.296 37.983 219.032 1.00 78.10 6
ATOM 1012 CB ILE B 274 56.803 37.978 220.481 1.00 78.20 6
ATOM 1013 CGl ILE B 274 55.898 36.757 220.660 1.00 78.50 6
ATOM 1014 CD ILE B 274 56.203 35.913 221.854 1.00 79.00 6
ATOM 1015 CG2 ILE B 274 56.033 39.244 220.821 1.00 78.17 6
ATOM 1016 C ILE B 274 57.560 39.357 218.408 1.00 77.96 6
ATOM 1017 O ILE B 274 56.733 39.867 217.651 1.00 78.16 8
ATOM 1018 N ASP B 275 58.741 39.905 218.660 1.00 77.63 7
ATOM 1019 CA ASP B 275 59.083 • 41.225 218.169 1.00 77.40 6
ATOM 1020 CB ASP B 275 60.301 41.749 218.931 1.00 77.56 6
ATOM 1021 CG ASP B 275 60.140 41.624 220.453 1.00 77.80 6
ATOM 1022 ODl ASP B 275 58.997 41.709 220.960 1.00 78.11 8
ATOM 1023 OD2 ASP B 275 61.158 41.427 221.147 1.00 78.09 8
ATOM 1024 C ASP B 275 59.287 41.207 216.656 1.00 77.11 6
ATOM 1025 O ASP B 275 58.951 42.173 215.970 1.00 77.25 8
ATOM 1026 N LYS B 276 59.806 40.096 216.138 1.00 76.72 7
ATOM 1027 CA LYS B 276 59.898 39.909 214.688 1.00 76.40 6
ATOM 1028 CB LYS B 276 60.563 38.583 214.319 1.00 76.63 6
ATOM 1029 CG LYS B 276 62.009 38.691 213.866 1.00 77.43 6
ATOM 1030 CD LYS B 276 62.244 39.874 212.939 1.00 77.90 6
ATOM 1031 CE LYS B 276 63.724 40.217 212.931 1.00 78.49 6
ATOM 1032 NZ LYS B 276 63.939 41.637 213.300 1.00 78.71 7
ATOM 1033 C LYS B 276 58.533 39.931 214.055 1.00 75.89 6
ATOM 1034 O LYS B 276 58.350 40.504 213.004 1.00 75.94 8
ATOM 1035 N LEU B 277 57.573 39.296 214.702 1.00 75.53 7
ATOM 1036 CA LEU B 277 56.263 39.160 214.110 1.00 75.08 6
ATOM 1037 CB LEU B 277 55.553 37.888 214.587 1.00 75.11 6
ATOM 1038 CG LEU B 277 56.172 36.496 214.302 1.00 74.93 6
ATOM 1039 CDl LEU B 277 55.064 35.479 213.977 1.00 74.34 6
ATOM 1040 CD2 LEU B 277 57.226 36.516 213.165 1.00 75.23 6
ATOM 1041 C LEU B 277 55.422 40.398 214.340 1.00 74.97 6
ATOM 1042 O LEU B 277 54.655 40.780 213.468 1.00 75.06 8
ATOM 1043 N LYS B 278 55.567 41.040 215.491 1.00 74.88 7
ATOM 1044 CA LYS B 278 54.883 42.299 215.696 1.00 74.81 6
ATOM 1045 CB LYS B 278 55.123 42.826 217.112 1.00 74.79 6
ATOM 1046 CG LYS B 278 54.331 42.073 218.194 1.00 74.11 6
ATOM 1047 CD LYS B 278 54.678 42.573 219.594 1.00 74.15 6 ATOM 1048 CE LYS B 278 53.545 42.321 220.592 ,00 73.19 6
ATOM 1049 NZ LYS B 278 53.952 42.624 222.008 ,00 71.81 7
ATOM 1050 C LYS B 278 55.347 43.256 214.588 ,00 75.31 6
ATOM 1051 O LYS B 278 54.527 43.828 213.863 ,00 75.33
ATOM 1052 N GLU B 279 56.663 43.351 214.415 1.00 75.72 7
ATOM 1053 CA GLU B 279 57.269 44.196 213.397 1.00 76.38 6
ATOM 1054 CB GLU B 279 58.801 44.155 213.537 1.00 76.50 6
ATOM 1055 CG GLU B 279 59.617 44.925 212.472 1 ,00 77.51 6
ATOM 1056 CD GLU B 279 61.117 44.572 212.490 1 ,00 77.60 6
ATOM 1057 OEl GLU B 279 61.511 43.570 213.141 1 ,00 78.98
ATOM 1058 OE2 GLU B 279 61.904 45.298 211.842 1 ,00 78.66
ATOM 1059 C GLU B 279 56.818 43.807 211.986 1 ,00 76.31
ATOM 1060 O GLU B 279 56.528 44.681 211.181 1 ,00 76.62
ATOM 1061 N GLU B 280 56.756 42.510 211.683 1 ,00 76.41 7
ATOM 1062 CA GLU B 280 56.321 42.069 210.352 1 ,00 76.31 6
ATOM 1063 CB GLU B 280 56.563 40.590 210.126 1 ,00 75.98 6
ATOM 1064 CG GLU B 280 57.955 40.285 209.667 1.00 75.93 6
ATOM 1065 CD GLU B 280 58.255 38.813 209.770 1.00 76.92 6
ATOM 1066 OEl GLU B 280 57.316 38.006 209.609 1.00 76.87
ATOM 1067 OE2 GLU B 280 59.424 38.455 210.026 1.00 77.78
ATOM 1068 C GLU B 280 54.864 42.411 210.096 1.00 76.53
ATOM 1069 O GLU B 280 54.527 42.878 209.014 1.00 76.67
ATOM 1070 N ALA B 281 54.003 42.207 211.088 1.00 76.73 7
ATOM 1071 CA ALA B 281 52.601 42.575 210.936 1.00 76.84 6
ATOM 1072 CB ALA B 281 51.768 41.981 212.044 1, 00 76.73 6
ATOM 1073 C ALA B 281 52.424 44.101 210.831 1.00 76.98 6
ATOM 1074 O ALA B 281 51.355 44.592 210.462 1.00 76.99 8
ATOM 1075 N GLU B 282 53.484 44.846 211.122 1.00 77.06 7
ATOM 1076 CA GLU B 282 53.467 46.276 210.887 1.00 77.26 6
ATOM 1077 CB GLU B 282 54.574 46.969 211.676 1.00 77.54 6
ATOM 1078 CG GLU B 282 54.186 48.357 212.147 1.00 79.01 6
ATOM 1079 CD GLU B 282 52.893 48.366 212.963 1.00 80.49 6
ATOM 1080 OEl GLU B 282 51.817 47.994 212.426 1.00 80.60
ATOM 1081 OE2 GLU B 282 52.959 48.760 214.148 1.00 81.06
ATOM 1082 C GLU B 282 53.525 46.626 209.396 1.00 77.10
ATOM 1083 O GLU B 282 52.716 47.414 208.916 1.00 77.14
ATOM 1084 N GLN B 283 54.460 46.020 208.669 1.00 77.00 7
ATOM 1085 CA GLN B 283 54.575 46.224 207.221 1.00 76.83 6
ATOM 1086 CB GLN B 283 55.939 45.740 206.707 1.00 77.18 6
ATOM 1087 CG GLN B 283 57.141 46.193 207.541 00 77.46
ATOM 1088 CD GLN B 283 58.200 45.110 207.662 00 77.89
ATOM 1089 OEl GLN B 283 58.510 44.646 208.761 00 78.18
ATOM 1090 NE2 GLN B 283 58.751 44.692 206.529 00 78.35 7
ATOM 1091 C GLN B 283 53.441 45.536 206.459 00 76.27 6
ATOM 1092 O GLN B 283 53.219 45.833 205.291 00 76.31 8
ATOM 1093 N HIS B 284 52.743 44.611 207.118 00 75.52 7
ATOM 1094 CA HIS B 284 51.561 43.996 206.533 00 74.97 6
ATOM 1095 CB HIS B 284 51.238 42.670 207.197 00 75.10 6
ATOM 1096 CG HIS B 284 52.332 41.665 207.079 00 75.87 6
ATOM 1097 NDl HIS B 284 52.553 40.692 208.031 00 77.26 7
ATOM 1098 CEI HIS B 284 53.591 39.959 207.670 00 76.88 6
ATOM 1099 NE2 HIS B 284 54.057 40.428 206.525 00 76.21 7
ATOM 1100 CD2 HIS B 284 53.290 41.499 206.138 00 75.90 6
ATOM 1101 C HIS B 284 50.383 44.928 206.669 00 74.37 6
ATOM 1102 O HIS B 284 49.545 45.033 205.771 00 74.33
ATOM 1103 N LYS B 285 50.320 45.609 207.803 1.00 73.53 ATOM 1104 CA LYS B 285 49.268 46.563 208.032 1.00 72.60 6
ATOM 1105 CB LYS B 285 49.382 47.149 209.431 1.00 72.89 6
ATOM 1106 CG LYS B 285 48.071 47.625 210.011 00 73.56
ATOM 1107 CD LYS B 285 48.311 48.410 211.284 00 74.04
ATOM 1108 CE LYS B 285 47.566 49.718 211.249 00 74.02
ATOM 1109 NZ LYS B 285 48.017 50.586 212.358 1.00 74.91
ATOM 1110 C LYS B 285 49.367 47.628 206.953 1 ,00 71.79
ATOM 1111 0 LYS B 285 48.396 47.859 206.231 1 ,00 71.75
ATOM 1112 N ILE B 286 50.552 48.217 206.784 1.00 70.70 7
ATOM 1113 CA ILE B 286 50.706 49.314 205.818 1.00 69.62 6
ATOM 1114 CB ILE B 286 51.924 50.250 206.108 1 ,00 69.49 6
ATOM 1115 CGl ILE B 286 53.165 49.438 206.498 1 ,00 69.93 6
ATOM 1116 CD ILE B 286 54.282 50.219 207.230 1.00 69.79 6
ATOM 1117 CG2 ILE B 286 51.547 51.270 207.186 1.00 68.93 6
ATOM 1118 C ILE B 286 50.524 48.948 204.337 1.00 68.84 6
ATOM 1119 O ILE B 286 50.348 49.835 203.520 1.00 68.89
ATOM 1120 N VAL B 287 50.514 47.661 203.995 1.00 67.87
ATOM 1121 CA VAL B 287 50.116 47.288 202.641 1.00 66.95
ATOM 1122 CB VAL B 287 50.887 46.081 202.035 1 ,00 66.83 6
ATOM 1123 CGl VAL B 287 52.354 46.128 202.400 1.00 66.33 6
ATOM 1124 CG2 VAL B 287 50.273 44.789 202.449 1.00 66.81 6
ATOM 1125 C VAL B 287 48.601 47.100 202.570 ,00 66.53 6
ATOM 1126 0 VAL B 287 47.977 47.437 201.554 ,00 66.63 8
ATOM 1127 N MET B 288 48.011 46.588 203.648 ,00 65.60 7
ATOM 1128 CA MET B 288 46.571 46.338 203.674 ,00 64.90 6
ATOM 1129 CB MET B 288 46.196 45.456 204.852 ,00 65.05 6
ATOM 1130 CG MET B 288 46.674 44.021 204.716 ,00 65.48 6
ATOM 1131 SD MET B 288 46.458 43.062 206.238 00 65.82 16
ATOM 1132 CE MET B 288 44.655 42.971 206.344 00 65.62 6
ATOM 1133 C MET B 288 45.768 47.631 203.700 1.00 63.99 6
ATOM 1134 O MET B 288 44.592 47.646 203.336 ,00 63.69
ATOM 1135 N GLU B 289 46.415 48.714 204.126 ,00 63.04 7
ATOM 1136 CA GLU B 289 45.824 50.043 204.022 ,00 62.18 6
ATOM 1137 CB GLU B 289 46.610 51.084 204.832 ,00 62.43 6
ATOM 1138 CG GLU B 289 47.608 50.519 205.860 ,00 64.75 6
ATOM 1139 CD GLU B 289 47.231 50.743 207.351 ,00 68.11 6
ATOM 1140 OEl GLU B 289 46.027 50.924 207.645 ,00 69.21
ATOM 1141 0E2 GLU B 289 48.145 50.730 208.234 ,00 68.26
ATOM 1142 C GLU B 289 45.712 50.506 202.561 ,00 61.05
ATOM 1143 0 GLU B 289 44.855 51.317 202.266 ,00 61.15
ATOM 1144 N THR B 290 46.552 50.001 201.650 ,00 59.51 7
ATOM 1145 CA THR B 290 46.584 50.563 200.299 00 58.05 6
ATOM 1146 CB THR B 290 47.921 50.363 199.570 ,00 58.19 6
ATOM 1147 OGl THR B 290 47.993 49.037 199.033 ,00 58.37 8
ATOM 1148 CG2 THR B 290 49.080 50.600 200.509 ,00 58.09 6
ATOM 1149 C THR B 290 45.477 49.968 199.519 00 57.49 6
ATOM 1150 O THR B 290 45.314 50.181 198.326 00 57.68 8
ATOM 1151 N VAL B 291 44.666 49.246 200.219 ,00 56.42 7
ATOM 1152 CA VAL B 291 43.718 48.486 199.483 ,00 55.71 6
ATOM 1153 CB VAL B 291 43.220 47.261 200.256 00 55.56 6
ATOM 1154 CGl VAL B 291 41.969 46.707 199.600 00 55.43 6
ATOM 1155 CG2 VAL B 291 44.306 46.204 200.310 ,00 54.82 6
ATOM 1156 C VAL B 291 42.552 49.347 199.060 ,00 55.33 6
ATOM 1157 0 VAL B 291 42.378 49.641 197.868 00 55.71 8
ATOM 1158 N PRO B 292 41.720 49.732 200.028 00 54.73 7
ATOM 1159 CA PRO B 292 40.521 50.486 199.688 1.00 54.28 6 ATOM 1160 CB PRO B 292 40.145 51.120 201.018 1.00 54.38 6
ATOM 1161 CG PRO B 292 40.523 50.044 202.006 00 54.24 6
ATOM 1162 CD PRO B 292 41.793 49.456 201.477 00 54.47 6
ATOM 1163 C PRO B 292 40.705 51.534 198.598 00 53.72 6
ATOM 1164 O PRO B 292 39.911 51.592 197.675 00 53.29 8
ATOM 1165 N VAL B 293 41.763 52.325 198.702 1.00 53.39 7
ATOM 1166 CA VAL B 293 42.062 53.332 197.70.5 ,00 53.05 6
ATOM 1167 CB VAL B 293 43.204 54.276 198.213 .00 53.33 6
ATOM 1168 CGl VAL B 293 44.530 53.502 198.503 .00 52.63 6
ATOM 1169 CG2 VAL B 293 43.389 55.463 197.270 .00 53.56 6
ATOM 1170 C VAL B 293 42.303 52.660 196.331 ,00 52.71 6
ATOM 1171 0 VAL B 293 41.619 52.992 195.346 ,00 52.66 8
ATOM 1172 N LEU B 294 43.237 51.704 196.309 .00 52.03 7
ATOM 1173 CA LEU B 294 43.530 50.872 195.166 1.00 51.42 6
ATOM 1174 CB LEU B 294 44.341 49.681 195.642 1.00 51.29 6
ATOM 1175 CG LEU B 294 45.821 49.605 195.327 1 ,00 52.20 6
ATOM 1176 CDl LEU B 294 45.935 49.186 193.870 1 ,00 53.41 6
ATOM 1177 CD2 LEU B 294 46.581 50.926 195.614 1.00 53.79 6
ATOM 1178 C LEU B 294 42.259 50.332 194.586 1.00 51.01 6
ATOM 1179 0 LEU B 294 41.973 50.511 193.399 1.00 51.36 8
ATOM 1180 N LYS B 295 41.482 49.668 195.425 1.00 50.27 7
ATOM 1181 CA LYS B 295 40.291 49.038 194.916 1.00 49.99 6
ATOM 1182 CB LYS B 295 39.535 48.286 195.985 1.00 49.83 6
ATOM 1183 CG LYS B 295 38.105 48.030 195.568 1.00 50.37 6
ATOM 1184 CD LYS B 295 37.650 46.632 195.890 1.00 52.74 6
ATOM 1185 CE LYS B 295 36.141 46.584 195.964 ,00 54.24 6
ATOM 1186 NZ LYS B 295 35.659 45.207 195.748 ,00 56.16 7
ATOM 1187 C LYS B 295 39.372 50.061 194.284 .00 49.78 6
ATOM 1188 O LYS B 295 38.936 49.903 193.146 .00 49.60 8
ATOM 1189. N ALA B 296 39.088 51.125 195.020 ,00 49.58 7
ATOM 1190 CA ALA B 296 38.144 52.104 194.551 ,00 49.02 6
ATOM 1191 CB ALA B 296 38.004 53.194 195.520 ,00 48.90 6
ATOM 1192 C ALA B 296 38.575 52.629 193.207 ,00 49.00 6
ATOM 1193 0 ALA B 296 37.763 52.661 192.298 1.00 49.49 8
ATOM 1194 N GLN B 297 39.842 53.007 193.065 ,00 48.68 7
ATOM 1195 CA GLN B 297 40.349 53.458 191.786 ,00 48.80 6
ATOM 1196 CB GLN B 297 41.842 53.558 191.871 ,00 48.95 6
ATOM 1197 CG GLN B 297 42.372 54.895 192.225 .00 50.82 6
ATOM 1198 CD GLN B 297 43.883 54.802 192.392 .00 54.01 6
ATOM 1199 OEl GLN B 297 44.632 54.969 191.416 ,00 55.82 8
ATOM 1200 NE2 GLN B 297 44.344 54.473 193.617 ,00 53.38 7
ATOM 1201 C GLN B 297 39.985 52.466 190.672 ,00 48.49 6
ATOM 1202 0 GLN B 297 39.303 52.829 189.675 ,00 48.61 8
ATOM 1203 N ALA B 298 40.432 51.220 190.860 ,00 47.57 7
ATOM 1204 CA ALA B 298 40.160 50.143 189.931 ,00 47.03 6
ATOM 1205 CB ALA B 298 40.479 48.830 190.580 ,00 46.90 6
ATOM 1206 C ALA B 298 38.691 50.192 189.511 ,00 46.81 6
ATOM 1207 0 ALA B 298 38.340 50.356 188.330 ,00 47.03
ATOM 1208 N ASP B 299 37.822 50.102 190.495 00 46.29 7
ATOM 1209 CA ASP B 299 36.419 50.110 190.206 00 46.02 6
ATOM 1210 CB ASP B 299 35.645 49.877 191.487 00 46.83 6
ATOM 1211 CG ASP B 299 35.892 48.485 192.037 ,00 48.73 6
ATOM 1212 ODl ASP B 299 36.270 47.580 191.228 ,00 49.88
ATOM 1213 0D2 ASP B 299 35.733 48.308 193.269 00 51.06
ATOM 1214 C ASP B 299 35.981 51.349 189.469 00 45.12
ATOM 1215 0 ASP B 299 35.308 51.230 188.459 1.00 45.22 ATOM 1216 N ILE B 300 36.393 52.519 189.937 1.00 44.09 7
ATOM 1217 CA ILE B 300 36.060 53.753 189.250 00 43.72 6
ATOM 1218 CB ILE B 300 36.694 54.977 189.931 00 43.59 6
ATOM 1219 CGl ILE B 300 35.762 55.546 190.987 00 43.28 6
ATOM 1220 CD ILE B 300 35.743 54.793 192.284 00 44.16 6
ATOM 1221 CG2 ILE B 300 36.898 56.096 188.944 00 43.97 6
ATOM 1222 C ILE B 300 36.452 53.704 187.769 00 43.60 6
ATOM 1223 0 ILE B 300 35.635 54.011 186.898 00 43.41 8
ATOM 1224 N TYR B 301 37.690 53.302 187.489 00 43.36 7
ATOM 1225 CA TYR B 301 38.197 53.302 186.123 00 43.35 6
ATOM 1226 CB TYR B 301 39.698 53.006 186.076 00 43.80 6
ATOM 1227 CG TYR B 301 40.600 54.066 186.707 00 45.04 6
ATOM 1228 CDl TYR B 301 41.526 53.722 187.671 00 44.37 6
ATOM 1229 CEI TYR B 301 42.342 54.671 188.251 00 44.78 6
ATOM 1230 CZ TYR B 301 42.259 55.988 187.870 00 45.46 6
ATOM 1231 OH TYR B 301 43.093 56.900 188.477 00 46.80 8
ATOM 1232 CE2 TYR B 301 41.357 56.384 186.906 00 45.30 6
ATOM 1233 CD2 TYR B 301 40.531 55.418 186.323 00 46.46 6
ATOM 1234 C TYR B 301 37.487 52.299 185.261 1.00 43.10 6
ATOM 1235 0 TYR B 301 37.150 52.590 184.123 1.00 43.59
ATOM 1236 N LYS B 302 37.275 51.101 185.785 1.00 42.64
ATOM 1237 CA LYS B 302 36.596 50.097 184.995 1.00 42.03
ATOM 1238 CB LYS B 302 36.556 48.749 185.701 1.00 41.54
ATOM 1239 CG LYS B 302 35.605 47.804 185.039 1.00 40.94 6
ATOM 1240 CD LYS B 302 35.862 46.391 185.411 1.00 41.71 6
ATOM 1241 CE LYS B 302 34.602 45.591 185.233 1.00 42.85 6
ATOM 1242 NZ LYS B 302 34.871 44.190 185.536 1.00 44.78 7
ATOM 1243 C LYS B 302 35.205 50.639 184.653 1.00 41.79 6
ATOM 1244 0 LYS B 302 34.814 50.716 183.482 1.00 41.49 8
ATOM 1245 N ALA B 303 34.492 51.086 185.673 1.00 41.76 7
ATOM 1246 CA ALA B 303 33.197 51.690 185.444 .00 41.88 6
ATOM 1247 CB ALA B 303 32.612 52.285 186.722 .00 42.11 6
ATOM 1248 C ALA B 303 33.301 52.756 184.368 .00 41.85 6
ATOM 1249 0 ALA B 303 32.404 52.845 183.540 .00 42.28
ATOM 1250 N ASP B 304 34.381 53.548 184.369 .00 41.58 7
ATOM 1251 CA ASP B 304 34.515 54.717 183.460 .00 41.51 6
ATOM 1252 CB ASP B 304 35.850 55.434 183.661 .00 41.69 6
ATOM 1253 CG ASP B 304 35.735 56.697 184.519 .00 44.65 6
ATOM 1254 ODl ASP B 304 36.675 56.953 185.319 .00 46.81
ATOM 1255 0D2 ASP B 304 34.721 57.442 184.398 .00 46.76
ATOM 1256 C ASP B 304 34.550 54.274 182.047 1.00 40.98
ATOM 1257 0 ASP B 304 33.808 54.761 181.177 1.00 41.29
ATOM 1258 N PHE B 305 35.475 53.358 181.824 1.00 40.21 7
ATOM 1259 CA PHE B 305 35.681 52.763 180.538 .00 39.45 6
ATOM 1260 CB PHE B 305 36.807 51.738 180.652 .00 39.05 6
ATOM 1261 CG PHE B 305 36.826 50.753 179.531 .00 38.86 6
ATOM 1262 CDl PHE B 305 37.541 51.019 178.374 .00 37.47 6
ATOM 1263 CEI PHE B 305 37.547 50.140 177.335 .00 37.04 6
ATOM 1264 CZ PHE B 305 36.834 48.971 177.419 .00 37.67 6
ATOM 1265 CE2 PHE B 305 36.112 48.686 178.565 .00 38.35 6
ATOM 1266 CD2 PHE B 305 36.104 49.573 179.615 .00 37.84 6
ATOM 1267 C PHE B 305 34.378 52.119 180.012 .00 39.28 6
ATOM 1268 0 PHE B 305 33.942 52.377 178.881 .00 38.93 8
ATOM 1269 N GLN B 306 33.749 51.288 180.830 .00 39.04 7
ATOM 1270 CA GLN B 306 32.586 50.602 180.332 .00 39.30 6
ATOM 1271 CB GLN B 306 32.007 49.734 181.419 1.00 39.64 6 ATOM 1272 CG GLN B 306 32.953 48.649 181.826 1.00 40.83 6
ATOM 1273 CD GLN B 306 32.341 47.804 182.885 1.00 44.16 6
ATOM 1274 OEl GLN B 306 31.868 46.716 182.597 1.00 46.09 8
ATOM 1275 NE2 GLN B 306 32.283 48.319 184.126 1.00 46.74 7
ATOM 1276 C GLN B 306 31.593 51.624 179.772 1.00 39.03 6
ATOM 1277 0 GLN B 306 31.066 51.448 178.663 1.00 39.11 8
ATOM 1278 N ALA B 307 31.409 52.714 180.521 1.00 38.65 7
ATOM 1279 CA ALA B 307 30.575 53.824 180.105 1.00 38.23 6
ATOM 1280 CB ALA B 307 30.526 54.875 181.165 1.00 38.13 6
ATOM 1281 C ALA B 307 31.070 54.403 178.782 1.00 38.20 6
ATOM 1282 0 ALA B 307 30.256 54.580 177.860 1.00 38.84 8
ATOM 1283 N GLU B 308 32.376 54.673 178.646 1.00 37.47 7
ATOM 1284 CA GLU B 308 32.892 55.133 177.324 1.00 36.90 6
ATOM 1285 CB GLU B 308 34.398 55.225 177.232 1.00 36.92 6
ATOM 1286 CG GLU B 308 35.014 56.446 177.787 1.00 38.12 6
ATOM 1287 CD GLU B 308 34.592 57.750 177.130 1.00 38.09 6
ATOM 1288 OEl GLU B 308 34.577 57.860 175.870 1.00 35.41 8
ATOM 1289 0E2 GLU B 308 34.316 58.685 177.936 1.00 38.58 8
ATOM 1290 C GLU B 308 32.542 54.195 176.205 1.00 36.58 6
ATOM 1291 0 GLU B 308 31.975 54.625 175.193 1.00 36.41 8
ATOM 1292 N ARG B 309 32.908 52.914 176.364 1.00 36.19 7
ATOM 1293 CA ARG B 309 32.663 51.953 175.294 1.00 35.52 6
ATOM 1294 CB ARG B 309 33.011 50.537 175.664 1.00 35.26 6
ATOM 1295 CG ARG B 309 32.884 49.632 174.477 1.00 33.84 6
ATOM 1296 CD ARG B 309 34.054 49.851 173.616 1.00 33.35 6
ATOM 1297 NE ARG B 309 34.874 48.658 173.584 1.00 35.40 7
ATOM 1298 CZ ARG B 309 36.148 48.627 173.204 1.00 37.19 6
ATOM 1299 NHl ARG B 309 36.756 49.742 172.842 1.00 37.42 7
ATOM 1300 NH2 ARG B 309 36.815 47.473 173.160 1.00 38.83 7
ATOM 1301 C ARG B 309 31.211 51.999 174.907 1.00 35.49 6
ATOM 1302 0 ARG B 309 30.889 52.034 173.713 1.00 35.68 8
ATOM 1303 N HIS B 310 30.341 52.034 175.917 1.00 34.98 7
ATOM 1304 CA HIS B 310 28.930 52.053 175.655 1.00 34.61 6
ATOM 1305 CB HIS B 310 28.140 52.168 176.931 1.00 34.23 6
ATOM 1306 CG HIS B 310 26.684 52.125 176.685 1.00 34.16 6
ATOM 1307 NDl HIS B 310 25.913 53.261 176.649 1.00 35.32 7
ATOM 1308 CEI HIS B 310 24.669 52.930 176.356 1.00 37.05 6
ATOM 1309 NE2 HIS B 310 24.620 51.624 176.166 1.00 36.92 7
ATOM 1310 CD2 HIS B 310 25.874 51.099 176.350 1.00 34.67 6
ATOM 1311 C HIS B 310 28.580 53.189 174.684 1.00 34.48 6
ATOM 1312 0 HIS B 310 27.908 52.958 173.650 1.00 34.89 8
ATOM 1313 N ALA B 311 29.074 54.389 175.004 1.00 33.62 7
ATOM 1314 CA ALA B 311 28.875 55.565 174.164 1.00 33.41 6
ATOM 1315 CB ALA B 311 29.408 56.807 174.848 1.00 33.21 6
ATOM 1316 C ALA B 311 29.565 55.378 172.815 1.00 33.50 6
ATOM 1317 0 ALA B 311 28.953 55.525 171.729 1.00 33.66 8
ATOM 1318 N ARG B 312 30.839 55.037 172.873 1.00 33.26 7
ATOM 1319 CA ARG B 312 31.585 54.854 171.647 1.00 33.71 6
ATOM 1320 CB ARG B 312 32.993 54.390 171.963 1.00 33.44 6
ATOM 1321 CG ARG B 312 33.833 54.153 170.745 1.00 32.77 6
ATOM 1322 CD ARG B 312 33.962 52.689 170.479 1.00 32.61 6
ATOM 1323 NE ARG B 312 34.778 52.445 169.300 1.00 32.74 7
ATOM 1324 CZ ARG B 312 36.073 52.167 169.316 1.00 31.55 6
ATOM 1325 NHl ARG B 312 36.719 52.083 170.459 1.00 31.53 7
ATOM 1326 NH2 ARG B 312 36.716 51.973 168.178 1.00 31.34 7
ATOM 1327 C ARG B 312 30.907 53.921 170.614 1.00 34.20 6 ATOM 1328 0 ARG B 312 31.039 54.102 169.409 1.00 33.66 8
ATOM 1329 N GLU B 313 30.183 52.916 171.086 1.00 34.91 7
ATOM 1330 CA GLU B 313 29.522 52.024 170.167 1.00 35.75 6
ATOM 1331 CB GLU B 313 29.069 50.765 170.876 1.00 35.96 6
ATOM 1332 CG GLU B 313 30.234 49.829 171.117 1.00 38.97 6
ATOM 1333 CD GLU B 313 29.882 48.623 171.969 1.00 44.28 6
ATOM 1334 OEl GLU B 313 29.174 48.774 172.998 1.00 46.98 8
ATOM 1335 0E2 GLU B 313 30.343 47.517 171.624 1.00 46.65 8
ATOM 1336 C GLU B 313 28.395 52.769 169.502 1.00 35.56 6
ATOM 1337 0 GLU B 313 28.391 52.887 168.284 1.00 35.47 8
ATOM 1338 N LYS B 314 27.502 53.340 170.316 1.00 35.58 7
ATOM 1339 CA LYS B 314 26.308 54.053 169.837 1.00 35.41 6
ATOM 1340 CB LYS B 314 25.598 54.744 170.998 1.00 35.01 6
ATOM 1341 CG LYS B 314 25.139 53.788 172.054 1.00 35.61 6
ATOM 1342 CD LYS B 314 24.429 54.484 173.194 1.00 36.90 6
ATOM 1343 CE LYS B 314 23.197 53.692 173.623 1.00 36.65 6
ATOM 1344 NZ LYS B 314 22.228 53.599 172.482 1.00 38.02 7
ATOM 1345 C LYS B 314 26.708 55.067 168.782 1.00 35.55 6
ATOM 1346 0 LYS B 314 26.005 55.253 167.782 1.00 35.05 8
ATOM 1347 N LEU B 315 27.863 55.701 169.031 1.00 35.90 7
ATOM 1348 CA LEU B 315 28.502 56.619 168.091 1.00 36.06 6
ATOM 1349 CB LEU B 315 29.733 57.273 168.712 1.00 35.55 6
ATOM 1350 CG LEU B 315 29.467 58.481 169.617 1.00 36.63 6
ATOM 1351 CDl LEU B 315 30.711 58.935 170.328 1.00 38.75 6
ATOM 1352 CD2 LEU B 315 28.946 59.657 168.848 1.00 37.41 6
ATOM 1353 C LEU B 315 28.891 55.897 166.814 1.00 36.36 6
ATOM 1354 0 LEU B 315 28.367 56.195 165.740 1.00 36.68 8
ATOM 1355 N VAL B 316 29.778 54.917 166.926 1.00 36.57 7
ATOM 1356 CA VAL B 316 30.230 54.213 165.745 1.00 36.73 6
ATOM 1357 CB VAL B 316 30.966 52.955 166.109 1.00 36.55 6
ATOM 1358 CGl VAL B 316 30.926 51.962 164.967 1.00 36.31 6
ATOM 1359 CG2 VAL B 316 32.380 53.315 166.424 1.00 37.11 6
ATOM 1360 C VAL B 316 29.029 53.896 164.898 1.00 37.24 6
ATOM 1361 0 VAL B 316 29.011 54.104 163.699 1.00 37.65 8
ATOM 1362 N GLU B 317 27.998 53.440 165.563 1.00 38.10 7
ATOM 1363 CA GLU B 317 26.768 53.058 164.935 1.00 39.28 6
ATOM 1364 CB GLU B 317 25.879 52.501 166.052 1.00 40.02 6
ATOM 1365 CG GLU B 317 24.424 52.724 165.968 1.00 43.02 6
ATOM 1366 CD GLU B 317 23.772 51.699 165.094 1.00 47.74 6
ATOM 1367 OEl GLU B 317 23.839 51.855 163.833 1.00 48.28 8
ATOM 1368 OE2 GLU B 317 23.190 50.745 165.686 1.00 49.58 8
ATOM 1369 C GLU B 317 26.175 54.263 164.210 1.00 39.25 6
ATOM 1370 0 GLU B 317 25.852 54.185 163.039 1.00 39.21 8
ATOM 1371 N LYS B 318 26.073 55.392 164.895 1.00 39.68 7
ATOM 1372 CA LYS B 318 25.515 56.578 164.276 1.00 39.94 6
ATOM 1373 CB LYS B 318 25.435 57.738 165.264 1.00 39.65 6
ATOM 1374 CG LYS B 318 24.500 58.824 164.817 1.00 37.85 6
ATOM 1375 CD LYS B 318 23.204 58.230 164.265 1.00 37.22 6
ATOM 1376 CE LYS B 318 22.189 57.915 165.345 1.00 36.18 6
ATOM 1377 NZ LYS B 318 20.828 57.948 164.797 1.00 34.71 7
ATOM 1378 C LYS B 318 26.353 56.988 163.084 1.00 40.75 6
ATOM 1379 0 LYS B 318 25.801 57.388 162.052 1.00 41.41 8
ATOM 1380 N LYS B 319 27.676 56.901 163.219 1.00 40.96 7
ATOM 1381 CA LYS B 319 28.539 57.290 162.119 1.00 41.60 6
ATOM 1382 CB LYS B 319 30.021 57.099 162.449 1.00 41.63 6
ATOM 1383 CG LYS B 319 30.963 57.401 161.257 1.00 43.27 6 ATOM 1384 CD LYS B 319 32.170 56.481 161.236 1.00 45.22 6
ATOM 1385 CE LYS B 319 31.757 54.999 161.468 1.00 48.29 6
ATOM 1386 NZ LYS B 319 32.876 53.968 161.456 1.00 47.72 7
ATOM 1387 C LYS B 319 28.155 56.493 160.875 1.00 41.79 6
ATOM 1388 0 LYS B 319 27.875 57.075 159.825 1.00 41.47 8
ATOM 1389 N GLU B 320 28.125 55.170 161.014 1.00 42.08 7
ATOM 1390 CA GLU B 320 27.737 54.291 159.933 1.00 43.06 6
ATOM 1391 CB GLU B 320 27.365 52.929 160.478 1.00 43.77 6
ATOM 1392 CG GLU B 320 28.104 51.755 159.898 1.00 46.62 6
ATOM 1393 CD GLU B 320 29.072 51.175 160.914 1.00 49.77 6
ATOM 1394 OEl GLU B 320 28.739 50.121 161.520 1.00 50.16 8
ATOM 1395 OE2 GLU B 320 30.142 51.803 161.122 1.00 50.83 8
ATOM 1396 C GLU B 320 26.493 54.846 159.286 1.00 43.02 6
ATOM 1397 0 GLU B 320 26.498 55.150 158.093 1.00 43.25 8
ATOM 1398 N TYR B 321 25.433 54.974 160.094 1.00 42.82 7
ATOM 1399 CA TYR B 321 24.137 55.488 159.661 1.00 42.60 6
ATOM 1400 CB TYR B 321 23.237 55.840 160.865 1.00 42.18 6
ATOM 1401 CG TYR B 321 21.916 56.473 160.451 1.00 41.79 6
ATOM 1402 CDl TYR B 321 20.853 55.683 160.002 1.00 41.67 6
ATOM 1403 CEI TYR B 321 19.657 56.244 159.588 1.00 40.71 6
ATOM 1404 CZ TYR B 321 19.510 57.608 159.620 1.00 40.89 6
ATOM 1405 OH TYR B 321 18.328 58.152 159.211 1.00 41.16 8
ATOM 1406 CE2 TYR B 321 20.535 58.425 160.063 1.00 41.25 6
ATOM 1407 CD2 TYR B 321 21.739 57.854 160.472 1.00 41.59 6
ATOM 1408 C TYR B 321 24.294 56.714 158.776 1.00 42.94 6
ATOM 1409 0 TYR B 321 23.783 56.758 157.663 1.00 43.06 8
ATOM 1410 N LEU B 322 25.001 57.714 159.274 1.00 43.24 7
ATOM 1411 CA LEU B 322 25.145 58.939 158.529 1.00 43.79 6
ATOM 1412 CB LEU B 322 25.827 60.003 159.383 1.00 43.47 6
ATOM 1413 CG LEU B 322 25.009 60.537 160.555 1.00 42.53 6
ATOM 1414 CDl LEU B 322 25.768 61.620 161.279 1.00 42.81 6
ATOM 1415 CD2 LEU B 322 23.693 61.086 160.081 1.00 40.92 6
ATOM 1416 C LEU B 322 25.875 58.728 157.202 1.00 44.86 6
ATOM 1417 0 LEU B 322 25.481 59.307 156.194 1.00 44.52 8
ATOM 1418 N GLN B 323 26.926 57.892 157.205 1.00 46.48 7
ATOM 1419 CA GLN B 323 27.697 57.580 155.979 1.00 47.79 6
ATOM 1420 CB GLN B 323 28.802 56.528 156.221 1.00 47.19 6
ATOM 1421 CG GLN B 323 30.225 57.111 156.362 1.00 48.44 6
ATOM 1422 CD GLN B 323 31.124 56.369 157.418 1.00 49.39 6
ATOM 1423 OEl GLN B 323 30.678 55.439 158.104 1.00 51.03 8
ATOM 1424 NE2 GLN B 323 32.393 56.801 157.537 1.00 50.41 7
ATOM 1425 C GLN B 323 26.705 57.119 154.926 1.00 48.27 6
ATOM 1426 0 GLN B 323 26.694 57.634 153.813 1.00 48.13 8
ATOM 1427 N GLU B 324 25.836 56.191 155.315 1.00 49.48 7
ATOM 1428 CA GLU B 324 24.833 55.651 154.421 1.00 51.23 6
ATOM 1429 CB GLU B 324 24.071 54.495 155.085 1.00 51.47 6
ATOM 1430 CG GLU B 324 24.853 53.157 155.036 1.00 55.79 6
ATOM 1431 CD GLU B 324 24.664 52.230 156.281 1.00 61.40 6
ATOM 1432 OEl GLU B 324 23.517 51.783 156.517 1.00 63.47 8
ATOM 1433 0E2 GLU B 324 25.662 51.916 157.008 1.00 63.09 8
ATOM 1434 C GLU B 324 23.915 56.756 153.920 1.00 51.64 6
ATOM 1435 0 GLU B 324 23.775 56.938 152.725 1.00 51.92 8
ATOM 1436 N GLN B 325 23.328 57.532 154.817 1.00 52.64 7
ATOM 1437 CA GLN B 325 22.469 58.641 154.385 1.00 53.72 6
ATOM 1438 CB GLN B 325 21.969 59.474 155.575 1.00 53.99 6
ATOM 1439 CG GLN B 325 21.073 58.723 156.566 1.00 54.63 6 ATOM 1440 CD GLN B 325 19.893 58.030 155.898 1.00 55.76 6
ATOM 1441 OEl GLN B 325 20.054 56.980 155.270 1.00 56.31 8
ATOM 1442 NE2 GLN B 325 18.699 58.610 156.037 1.00 56.03 7
ATOM 1443 C GLN B 325 23.163 59.535 153.363 1.00 54.30 6
ATOM 1444 0 GLN B 325 22.559 59.921 152.378 1.00 54.30 8
ATOM 1445 N LEU B 326 24.437 59.836 153.596 1.00 55.35 7
ATOM 1446 CA LEU B 326 25.209 60.661 152.684 1.00 56.25 6
ATOM 1447 CB LEU B 326 26.532 61.085 153.335 1.00 55.97 6
ATOM 1448 CG LEU B 326 27.162 62.464 153.081 1.00 55.52 6
ATOM 1449 CDl LEU B 326 28.034 62.470 151.815 1.00 56.45 6
ATOM 1450 CD2 LEU B 326 26.136 63.607 153.065 1.00 54.51 6
ATOM 1451 C LEU B 326 25.442 59.945 151.349 1.00 57.39 6
ATOM 1452 0 LEU B 326 25.482 60.602 150.311 1.00 57.73 8
ATOM 1453 N GLU B 327 25.591 58.615 151.368 1.00 58.58 7
ATOM 1454 CA GLU B 327 25.681 57.845 150.128 1.00 60.00 6
ATOM 1455 CB GLU B 327 25.895 56.361 150.384 1.00 60.00 6
ATOM 1456 CG GLU B 327 27.175 55.802 149.812 1.00 61.00 6
ATOM 1457 CD GLU B 327 28.338 55.861 150.796 1.00 62.50 6
ATOM 1458 OEl GLU B 327 28.151 55.517 151.986 1.00 62.43 8
ATOM 1459 OE2 GLU B 327 29.454 56.235 150.369 1.00 63.52 8
ATOM 1460 C GLU B 327 24.409 58.020 149.333 1.00 61.06 6
ATOM 1461 0 GLU B 327 24.414 58.680 148.303 1.00 61.52 8
ATOM 1462 N GLN B 328 23.315 57.444 149.822 1.00 62.40 7
ATOM 1463 CA GLN B 328 21.985 57.593 149.206 1.00 64.02 6
ATOM 1464 CB GLN B 328 20.867 57.357 150.218 1.00 63.91 6
ATOM 1465 CG GLN B 328 21.114 56.248 151.184 1.00 66.20 6
ATOM 1466 CD GLN B 328 20.677 54.907 150.664 1.00 68.96 6
ATOM 1467 OEl GLN B 328 19.941 54.187 151.341 1.00 70.32 8
ATOM 1468 NE2 GLN B 328 21.124 54.551 149.458 1.00 70.02 7
ATOM 1469 C GLN B 328 21.719 58.972 148.641 1.00 64.74 6
ATOM 1470 0 GLN B 328 21.246 59.118 147.522 1.00 64.97 8
ATOM 1471 N LEU B 329 21.984 59.994 149.434 1.00 65.70 7
ATOM 1472 CA LEU B 329 21.604 61.304 149.014 1.00 66.60 6
ATOM 1473 CB LEU B 329 21.557 62.268 150.171 1.00 66.23 6
ATOM 1474 CG LEU B 329 20.183 62.885 150.362 1.00 65.38 6
ATOM 1475 CDl LEU B 329 20.363 64.258 150.964 1.00 65.09 6
ATOM 1476 CD2 LEU B 329 19.409 62.954 149.059 1.00 64.54 6
ATOM 1477 C LEU B 329 22.526 61.804 147.940 1.00 67.86 6
ATOM 1478 0 LEU B 329 22.055 62.411 146.998 1.00 68.16 8
ATOM 1479 N GLN B 330 23.826 61.538 148.048 1.00 69.76 7
ATOM 1480 CA GLN B 330 24.759 61.993 147.000 1.00 71.11 6
ATOM 1481 CB GLN B 330 26.235 61.977 147.457 1.00 71.23 6
ATOM 1482 CG GLN B 330 27.277 62.386 146.364 1.00 71.34 6
ATOM 1483 CD GLN B 330 27.436 63.910 146.110 1.00 72.70 6
ATOM 1484 OEl GLN B 330 26.486 64.694 146.202 1.00 72.75 8
ATOM 1485 NE2 GLN B 330 28.657 64.311 145.758 1.00 72.57 7
ATOM 1486 C GLN B 330 24.529 61.234 145.688 1.00 72.02 6
ATOM 1487 0 GLN B 330 24.907 61.710 144.618 1.00 72.08 8
ATOM 1488 N ARG B 331 23.877 60.075 145.796 1.00 73.20 7
ATOM 1489 CA ARG B 331 23.396 59.278 144.664 1.00 74.46 6
ATOM 1490 CB ARG B 331 22.900 57.933 145.202 1.00 74.10 6
ATOM 1491 CG ARG B 331 22.662 56.817 144.190 1.00 73.35 6
ATOM 1492 CD ARG B 331 23.767 55.737 144.203 1.00 71.89 6
ATOM 1493 NE ARG B 331 24.413 55.522 145.512 1.00 70.93 7
ATOM 1494 CZ ARG B 331 23.920 54.808 146.534 1.00 70.02 6
ATOM 1495 NHl ARG B 331 22.732 54.214 146.450 1.00 69.16 7 ATOM 1496 NH2 ARG B 331 24.627 54.694 147.661 1.00 69.42 7
ATOM 1497 C ARG B 331 22.234 59.979 143.952 1.00 75.75 6
ATOM 1498 0 ARG B 331 22.019 59.796 142.751 1.00 75.92 8
ATOM 1499 N GLU B 332 21.480 60.768 144.710 1.00 77.22 7
ATOM 1500 CA GLU B 332 20.285 61.423 144.196 1.00 78.93 6
ATOM 1501 CB GLU B 332 19.255 61.603 145.307 1.00 78.98 6
ATOM 1502 CG GLU B 332 17.982 60.814 145.106 1.00 79.82 6
ATOM 1503 CD GLU B 332 18.197 59.315 145.070 1.00 81.26 6
ATOM 1504 OEl GLU B 332 19.313 58.863 144.735 1.00 82.51 8
ATOM 1505 0E2 GLU B 332 17.238 58.578 145.374 1.00 81.73 8
ATOM 1506 C GLU B 332 20.572 62.750 143.537 1.00 79.91 6
ATOM 1507 0 GLU B 332 20.049 63.048 142.467 1.00 80.09 8
ATOM 1508 N PHE B 333 21.394 63.552 144.192 1.00 81.19 7
ATOM 1509 CA PHE B 333 21.881 64.787 143.616 1.00 82.52 6
ATOM 1510 CB PHE B 333 22.660 65.545 144.693 1.00 82.67 6
ATOM 1511 CG PHE B 333 22.895 66.997 144.395 1.00 82.82 6
ATOM 1512 CDl PHE B 333 21.834 67.895 144.333 1.00 83.07 6
ATOM 1513 CEI PHE B 333 22.063 69.251 144.063 1.00 83.67 6
ATOM 1514 CZ PHE B 333 23.374 69.720 143.879 1.00 83.48 6
ATOM 1515 CE2 PHE B 333 24.447 68.831 143.971 1.00 83.81 6
ATOM 1516 CD2 PHE B 333 24.199 67.477 144.233 1.00 83.48 6
ATOM 1517 C PHE B 333 22.742 64.461 142.373 1.00 83.46 6
ATOM 1518 0 PHE B 333 23.175 65.362 141.652 1.00 83.74 8
ATOM 1519 N ASN B 334 22.943 63.161 142.123 1.00 84.37 7
ATOM 1520 CA ASN B 334 23.702 62.630 140.982 1.00 85.16 6
ATOM 1521 CB ASN B 334 24.441 61.368 141.419 1.00 84.80 6
ATOM 1522 CG ASN B 334 25.913 61.583 141.580 1.00 84.10 6
ATOM 1523 ODl ASN B 334 26.356 62.574 142.157 1.00 83.22 8
ATOM 1524 ND2 ASN B 334 26.693 60.648 141.066 1.00 83.61 7
ATOM 1525 C ASN B 334 22.847 62.236 139.784 1.00 86.03 6
ATOM 1526 0 ASN B 334 23.217 62.462 138.628 1.00 86.13 8
ATOM 1527 N LYS B 335 21.724 61.592 140.079 1.00 87.20 7
ATOM 1528 CA LYS B 335 20.778 61.156 139.059 1.00 88.31 6
ATOM 1529 CB LYS B 335 19.863 60.053 139.602 1.00 88.28 6
ATOM 1530 CG LYS B 335 20.587 58.736 139.795 1.00 88.75 6
ATOM 1531 CD LYS B 335 19.748 57.698 140.506 1.00 88.96 6
ATOM 1532 CE LYS B 335 20.604 56.470 140.773 1.00 89.05 6
ATOM 1533 NZ LYS B 335 19.804 55.314 141.231 1.00 89.30 7
ATOM 1534 C LYS B 335 19.951 62.334 138.596 1.00 88.96 6
ATOM 1535 0 LYS B 335 19.738 62.522 137.400 1.00 89.13 8
ATOM 1536 N LEU B 336 19.494 63.132 139.553 1.00 89.86 7
ATOM 1537 CA LEU B 336 18.760 64.355 139.241 1.00 90.67 6
ATOM 1538 CB LEU B 336 17.674 64.642 140.290 1.00 90.69 6
ATOM 1539 CG LEU B 336 16.579 63.599 140.557 1.00 90.76 6
ATOM 1540 CDl LEU B 336 17.083 62.455 141.459 1.00 90.39 6
ATOM 1541 CD2 LEU B 336 15.329 64.258 141.157 1.00 90.48 6
ATOM 1542 C LEU B 336 19.731 65.539 139.093 1.00 91.31 6
ATOM 1543 0 LEU B 336 19.348 66.702 139.314 1.00 91.36 8
ATOM 1544 N LYS B 337 20.976 65.211 138.710 1.00 91.90 7
ATOM 1545 CA LYS B 337 22.073 66.165 138.429 1.00 92.33 6
ATOM 1546 CB LYS B 337 23.207 65.473 137.638 1.00 92.29 6
ATOM 1547 CG LYS B 337 24.150 66.407 136.861 1.00 91.99 6
ATOM 1548 CD LYS B 337 25.549 65.828 136.753 1.00 91.67 6
ATOM 1549 CE LYS B 337 26.487 66.799 136.059 1.00 91.01 6
ATOM 1550 NZ LYS B 337 27.893 66.364 136.238 1.00 90.54 7
ATOM 1551 C LYS B 337 21.618 67.421 137.693 1.00 92.66 6 ATOM 1552 0 LYS B 337 20.773 67.391 136.792 1.00 92.93 8
ATOM 1553 OXT LYS B 337 22.071 68.516 138.044 1.00 92.86 8
ATOM 1554 N SER C 12 -1.952 44.539 167.423 1.00 71.74 7
ATOM 1555 CA SER C 12 -0.990 44.950 168.497 1.00 71.74 6
ATOM 1556 CB SER C 12 -1.061 44.018 169.724 1.00 71.76 6
ATOM 1557 OG SER C 12 -1.010 42.643 169.376 1.00 71.83 8
ATOM 1558 C SER C 12 0.451 45.129 167.996 1.00 71.46 6
ATOM 1559 0 SER C 12 1.281 45.739 168.676 1.00 71.38 8
ATOM 1560 N ASP C 13 0.744 44.617 166.802 1.00 70.95 7
ATOM 1561 CA ASP C 13 2.040 44.881 166.179 1.00 70.31 6
ATOM 1562 CB ASP C 13 2.528 43.701 165.325 1.00 70.52 6
ATOM 1563 CG ASP C 13 2.379 43.951 163.829 1.00 71.36 6
ATOM 1564 ODl ASP C 13 3.405 44.260 163.173 1.00 72.42 8
ATOM 1565 0D2 ASP C 13 1.242 43.854 163.316 1.00 71.46 8
ATOM 1566 C ASP C 13 1.993 46.220 165.411 1.00 69.34 6
ATOM 1567 0 ASP C 13 2.891 46.555 164.630 1.00 69.13 8
ATOM 1568 N LEU C 14 0.937 46.992 165.655 1.00 67.97 7
ATOM 1569 CA LEU C 14 0.971 48.400 165.329 1.00 66.48 6
ATOM 1570 CB LEU C 14 -0.312 49.109 165.753 1.00 66.48 6
ATOM 1571 CG LEU C 14 -1.547 48.779 164.907 1.00 66.37 6
ATOM 1572 CDl LEU C 14 -2.667 49.803 165.128 1.00 66.16 6
ATOM 1573 CD2 LEU C 14 -1.188 48.672 163.425 1.00 65.71 6
ATOM 1574 C LEU C 14 2.192 49.005 166.015 1.00 65.59 6
ATOM 1575 O LEU C 14 2.867 49.857 165.434 1.00 65.73 8
ATOM 1576 N GLY C 15 2.495 48.528 167.228 1.00 64.28 7
ATOM 1577 CA GLY C 15 3.707 48.922 167.961 1.00 62.51 6
ATOM 1578 C GLY C 15 5.000 48.830 167.164 1.00 61.28 6
ATOM 1579 O GLY C 15 5.773 49.790 167.092 1.00 61.06 8
ATOM 1580 N LYS C 16 5.218 47.667 166.556 1.00 60.20 7
ATOM 1581 CA LYS C 16 6.383 47.391 165.704 1.00 58.94 6
ATOM 1582 CB LYS C 16 6.287 45.951 165.173 1.00 59.00 6
ATOM 1583 CG LYS C 16 7.571 45.351 164.641 1.00 58.67 6
ATOM 1584 CD LYS C 16 7.319 43.995 164.003 1.00 58.85 6
ATOM 1585 CE LYS C 16 8.627 43.253 163.747 1.00 58.98 6
ATOM 1586 NZ LYS C 16 8.498 42.206 162.684 1.00 58.97 7
ATOM 1587 C LYS C 16 6.487 48.367 164.532 1.00 58.25 6
ATOM 1588 O LYS C 16 7.588 48.699 164.087 1.00 57.71 8
ATOM 1589 N LYS C 17 5.333 48.809 164.028 1.00 57.78 7
ATOM 1590 CA LYS C 17 5.305 49.741 162.893 1.00 57.39 6
ATOM 1591 CB LYS C 17 4.036 49.581 162.040 1.00 57.41 6
ATOM 1592 CG LYS C 17 3.897 48.204 161.356 1.00 57.84 6
ATOM 1593 CD LYS C 17 5.118 47.816 160.502 1.00 58.71 6
ATOM 1594 CE LYS C 17 5.162 46.309 160.230 1.00 58.37 6
ATOM 1595 NZ LYS C 17 4.216 45.921 159.145 1.00 58.82 7
ATOM 1596 C LYS C 17 5.536 51.188 163.326 1.00 56.83 6
ATOM 1597 0 LYS C 17 6.221 51.951 162.624 1.00 56.52 8
ATOM 1598 N LEU C 18 4.989 51.548 164.487 1.00 56.14 7
ATOM 1599 CA LEU C 18 5.225 52.861 165.056 1.00 55.66 6
ATOM 1600 CB LEU C 18 4.340 53.090 166.279 1.00 55.42 6
ATOM 1601 CG LEU C 18 4.553 54.349 167.124 1.00 55.02 6
ATOM 1602 CDl LEU C 18 4.482 55.612 166.308 1.00 54.24 6
ATOM 1603 CD2 LEU C 18 3.530 54.396 168.245 1.00 55.55 6
ATOM 1604 C LEU C 18 6.708 53.051 165.374 1.00 55.70 6
ATOM 1605 0 LEU C 18 7.263 54.126 165.137 1.00 55.84 8
ATOM 1606 N LEU C 19 7.355 52.005 165.876 1.00 55.62 7
ATOM 1607 CA LEU C 19 8.794 52.071 166.112 1.00 55.90 6 ATOM 1608 CB LEU C 19 9.318 50.749 166.673 1.00 55.85 6
ATOM 1609 CG LEU C 19 8.833 50.292 168.046 1.00 55.50 6
ATOM 1610 CDl LEU C 19 9.421 48.932 168.370 1.00 54.93 6
ATOM 1611 CD2 LEU C 19 9.190 51.306 169.121 1.00 55.56 6
ATOM 1612 C LEU C 19 9.548 52.432 164.832 1.00 56.28 6
ATOM 1613 0 LEU C 19 10.344 53.369 164.809 1.00 55.98 8
ATOM 1614 N GLU C 20 9.257 51.687 163.769 1.00 57.01 7
ATOM 1615 CA GLU C 20 9.865 51.875 162.451 1.00 57.78 6
ATOM 1616 CB GLU C 20 9.246 50.909 161.444 1.00 58.21 6
ATOM 1617 CG GLU C 20 10.291 50.122 160.691 1.00 61.13 6
ATOM 1618 CD GLU C 20 10.938 49.067 161.591 1.00 64.71 6
ATOM 1619 OEl GLU C 20 10.166 48.359 162.306 1.00 67.07 8
ATOM 1620 0E2 GLU C 20 12.198 48.961 161.594 1.00 65.04 8
ATOM 1621 C GLU C 20 9.654 53.271 161.920 1.00 57.24 6
ATOM 1622 0 GLU C 20 10.573 53.887 161.387 1.00 57.00 8
ATOM 1623 N ALA C 21 8.417 53.742 162.055 1.00 56.95 7
ATOM 1624 CA ALA C 21 8.016 55.050 161.577 1.00 56.58 6
ATOM 1625 CB ALA C 21 6.532 55.255 161.805 1.00 56.47 6
ATOM 1626 C ALA C 21 8.814 56.123 162.286 1.00 56.42 6
ATOM 1627 0 ALA C 21 9.279 57.072 161.663 1.00 56.26 8
ATOM 1628 N ALA C 22 8.982 55.950 163.592 1.00 56.46 7
ATOM 1629 CA ALA C 22 9.727 56.895 164.413 1.00 56.50 6
ATOM 1630 CB ALA C 22 9.552 56.573 165.871 1.00 56.37 6
ATOM 1631 C ALA C 22 11.215 56.959 164.048 1.00 56.64 6
ATOM 1632 0 ALA C 22 11.783 58.044 163.981 1.00 56.54 8
ATOM 1633 N ARG C 23 11.847 55.807 163.818 1.00 56.79 7
ATOM 1634 CA ARG C 23 13.231 55.792 163.356 1.00 57.25 6
ATOM 1635 CB ARG C 23 13.777 54.367 163.242 1.00 56.85 6
ATOM 1636 CG ARG C 23 15.239 54.303 162.751 1.00 58.13 6
ATOM 1637 CD ARG C 23 15.775 52.885 162.469 1.00 58.74 6
ATOM 1638 NE ARG C 23 15.285 51.911 163.446 1.00 62.17 7
ATOM 1639 CZ ARG C 23 14.436 50.919 163.168 1.00 63.14 6
ATOM 1640 NHl ARG C 23 13.995 50.731 161.925 1.00 62.45 7
ATOM 1641 NH2 ARG C 23 14.032 50.101 164.136 1.00 63.69 7
ATOM 1642 C ARG C 23 13.326 56.481 161.999 1.00 57.16 6
ATOM 1643 0 ARG C 23 14.251 57.261 161.752 1.00 57.07 8
ATOM 1644 N ALA C 24 12.354 56.198 161.130 1.00 57.36 7
ATOM 1645 CA ALA C 24 12.414 56.612 159.727 1.00 57.41 6
ATOM 1646 CB ALA C 24 11.484 55.778 158.891 1.00 57.20 6
ATOM 1647 C ALA C 24 12.125 58.087 159.520 1.00 57.61 6
ATOM 1648 0 ALA C 24 12.657 58.694 158.596 1.00 57.82 8
ATOM 1649 N GLY C 25 11.294 58.666 160.375 1.00 57.82 7
ATOM 1650 CA GLY C 25 10.952 60.070 160.234 1.00 58.27 6
ATOM 1651 C GLY C 25 9.623 60.268 159.540 1.00 58.64 6
ATOM 1652 0 GLY C 25 9.217 61.399 159.285 1.00 58.45 8
ATOM 1653 N GLN C 26 8.943 59.162 159.250 1.00 59.21 7
ATOM 1654 CA GLN C 26 7.611 59.185 158.649 1.00 60.13 6
ATOM 1655 CB GLN C 26 7.119 57.767 158.323 1.00 60.19 6
ATOM 1656 CG GLN C 26 8.167 56.748 157.894 1.00 61.44 6
ATOM 1657 CD GLN C 26 8.851 57.093 156.578 1.00 63.51 6
ATOM 1658 OEl GLN C 26 8.441 58.014 155.864 1.00 64.05 8
ATOM 1659 NE2 GLN C 26 9.903 56.340 156.244 1.00 64.54 7
ATOM 1660 C GLN C 26 6.585 59.845 159.567 1.00 60.63 6
ATOM 1661 0 GLN C 26 5.865 59.160 160.290 1.00 60.50 8
ATOM 1662 N ASP C 27 6.531 61.175 159.518 1.00 61.51 7
ATOM 1663 CA ASP C 27 5.556 61.999 160.249 1.00 62.24 6 ATOM 1664 CB ASP C 27 5.597 63.443 159.730 00 62.61
ATOM 1665 CG ASP C 27 6.743 64.249 160.313 00 64.07
ATOM 1666 ODl ASP C 27 7.926 63.820 160.213 1.00 64.69
ATOM 1667 OD2 ASP C 27 6.442 65.333 160.862 00 65.47
ATOM 1668 C ASP C 27 4.132 61.526 160.079 00 62.22
ATOM 1669 O ASP C 27 3.412 61.327 161.053 00 62.46
ATOM 1670 N ASP C 28 3.716 61.394 158.826 00 62.23 7
ATOM 1671 CA ASP C 28 2.347 61.002 158.519 00 62.39 6
ATOM 1672 CB ASP C 28 2.028 61.172 157.033 00 62.62 6
ATOM 1673 CG ASP C 28 3.254 60.999 156.139 1.00 64.05 6
ATOM 1674 ODl ASP C 28 3.126 61.345 154.938 00 65.74
ATOM 1675 0D2 ASP C 28 4.330 60.537 156.617 00 63.80
ATOM 1676 C ASP C 28 2.057 59.585 158.972 00 62.04
ATOM 1677 O ASP C 28 0.972 59.318 159.467 00 62.18
ATOM 1678 N GLU C 29 3.028 58.687 158.818 00 61.72 7
ATOM 1679 CA GLU C 29 2.859 57.302 159.265 00 61.35 6
ATOM 1680 CB GLU C 29 4.040 56.414 158.873 00 61.74 6
ATOM 1681 CG GLU C 29 4.126 56.080 157.383 00 63.75 6
ATOM 1682 CD GLU C 29 3.125 55.029 156.933 00 65.79 6
ATOM 1683 OEl GLU C 29 3.146 54.693 155.724 00 66.39
ATOM 1684 0E2 GLU C 29 2.330 54.547 157.778 00 66.31
ATOM 1685 C GLU C 29 690 57.258 160.763 00 60.50
ATOM 1686 O GLU C 29 881 56.492 161.271 00 60.56
ATOM 1687 N VAL C 30 460 58.089 161.462 00 59.42 7
ATOM 1688 CA VAL C 30 371 58.194 162.913 00 58.17 6
ATOM 1689 CB VAL C 30 442 59.179 163.501 00 58.09 6
ATOM 1690 CGl VAL C 30 045 59.695 164.872 00 57.33 6
ATOM 1691 CG2 VAL C 30 5.827 58.525 163.546 00 57.29 6
ATOM 1692 C VAL C 30 1.944 58.582 163.282 00 57.74 6
ATOM 1693 O VAL C 30 1.274 57.837 163.991 00 57.46
ATOM 1694 N ARG C 31 1.464 59.708 162.755 1.00 57.35 7
ATOM 1695 CA ARG C 31 0.131 60.184 163.124 00 57.25 6
ATOM 1696 CB ARG C 31 0.098 61.660 162.782 00 57.15 6
ATOM 1697 CG ARG C 31 0.165 62.548 164.037 00 57.68 6
ATOM 1698 CD ARG C 31 0.448 64.000 163.708 00 57.91 6
ATOM 1699 NE ARG C 31 0.750 64.831 163.549 00 59.50 7
ATOM 1700 CZ ARG C 31 1.586 64.805 162.507 00 60.09 6
ATOM 1701 NHl ARG C 31 404 63.960 161.503 1.00 60.61 7
ATOM 1702 NH2 ARG C 31 627 65.626 162.472 1.00 60.03 7
ATOM 1703 C ARG C 31 009 59.287 162.654 1.00 56.82
ATOM 1704 0 ARG C 31 057 59.243 163.300 1.00 56.57
ATOM 1705 N ILE C 32 -0.782 58.563 161.556 1.00 56.62 7
ATOM 1706 CA ILE C 32 -1 696 57.509 161.084 1.00 56.34 6
ATOM 1707 CB ILE C 32 1.263 56.912 159.696 1.00 56.30 6
ATOM 1708 CGl ILE C 32 1.784 57.773 158.537 1 ,00 55.84 6
ATOM 1709 CD ILE C 32 -3, 260 57.581 158.203 1.00 55.29 6
ATOM 1710 CG2 ILE C 32 -1.709 55.439 159.534 1.00 55.88 6
ATOM 1711 C ILE C 32 -1.766 56.394 162.114 1 ,00 56.32
ATOM 1712 0 ILE C 32 -2.838 55.893 162.428 1 ,00 56.45
ATOM 1713 N LEU C 33 0.610 56.015 162.642 1 ,00 56.35 7
ATOM 1714 CA LEU C 33 0.535 54.953 163.633 1.00 56.29 6
ATOM 1715 CB LEU C 33 0.906 54.426 163.731 1 ,00 56.21 6
ATOM 1716 CG LEU C 33 1.262 53.436 162.601 1 ,00 55.63 6
ATOM 1717 CDl LEU C 33 2.609 53.700 161.948 1.00 55.89 6
ATOM 1718 CD2 LEU C 33 1.187 52.001 163.075 1.00 54.90 6
ATOM 1719 C LEU C 33 1.094 55.425 164.978 1.00 56.42 6 ATOM 1720 0 LEU C 33 1.673 54.644 165.738 00 56.16
ATOM 1721 N MET C 34 0.935 56.719 165.244 00 56.80 7
ATOM 1722 CA MET C 34 1.564 57.353 166.391 00 57.23 6
ATOM 1723 CB MET C 34 -1 148 58.823 166.504 00 57.51 6
ATOM 1724 CG MET C 34 0.330 59.035 166.799 00 58.59 6
ATOM 1725 SD MET C 34 0.875 58.571 168.463 00 61.62 16
ATOM 1726 CE MET C 34 0.026 57.005 168.760 00 61.15 6
ATOM 1727 C MET C 34 -3.078 57.235 166.301 00 57.18 6
ATOM 1728 0 MET C 34 -3.704 56.781 167.249 00 57.49
ATOM 1729 N ALA C 35 -3.658 57.623 165.162 00 56.93 7
ATOM 1730 CA ALA C 35 -5.112 57.553 164.971 1.00 56.54 6
ATOM 1731 CB ALA C 35 -5.526 58.186 163.655 1.00 56.60
ATOM 1732 C ALA C 35 -5.677 56.129 165.093 1.00 56.34
ATOM 1733 O ALA C 35 6.784 55.951 165.605 1.00 56.61
ATOM 1734 N ASN C 36 4.916 55.130 164.633 1.00 55.85 7
ATOM 1735 CA ASN C 36 -5 286 53.706 164.775 1.00 55.21 6
ATOM 1736 CB ASN C 36 4.566 52.822 163.738 00 55.03 6
ATOM 1737 CG ASN C 36 5.116 52.978 162.327 00 54.58 6
ATOM 1738 ODl ASN C 36 6.290 53.287 162.121 1.00 54.61 8
ATOM 1739 ND2 ASN C 36 260 52.746 161.344 ,00 53.98 7
ATOM 1740 C ASN C 36 992 53.166 166.169 .00 55.03 6
ATOM 1741 0 ASN C 36 064 51.961 166.398 .00 55.13
ATOM 1742 N GLY C 37 629 54.066 167.080 .00 54.85 7
ATOM 1743 CA GLY C 37 4.318 53.731 168.472 .00 54.31 6
ATOM 1744 C GLY C 37 -3.069 52.912 168.758 .00 53.85 6
ATOM 1745 0 GLY C 37 -3.061 52.150 169.717 1.00 53.84
ATOM 1746 N ALA C 38 2.012 53.056 167.957 1.00 53.56
ATOM 1747 CA ALA C 38 0.754 52.363 168.269 1.00 53.25
ATOM 1748 CB ALA C 38 0.274 52.552 167.173 1.00 53.22 6
ATOM 1749 C ALA C 38 0.213 52.844 169.617 1.00 52.99 6
ATOM 1750 0 ALA C 38 0.430 53.998 170.006 00 53.06 8
ATOM 1751 N ASP C 39 0.459 51.952 170.338 00 52.56 7
ATOM 1752 CA ASP C 39 0.933 52.289 171.674 00 52.44 6
ATOM 1753 CB ASP C 39 1.229 51.038 172.504 00 52.59 6
ATOM 1754 CG ASP C 39 1.752 51.377 173.896 00 53.05 6
ATOM 1755 ODl ASP C 39 1.594 52.540 174.345 00 53.09
ATOM 1756 0D2 ASP C 39 2.323 50.478 174.545 00 54.03
ATOM 1757 C ASP C 39 2.162 53.189 171.632 00 52.15
ATOM 1758 0 ASP C 39 3.220 52.781 171.164 1.00 52.36
ATOM 1759 N VAL C 40 2.011 54.402 172.160 1.00 51.52 7
ATOM 1760 CA VAL C 40 3.059 55.413 172.123 1.00 50.83 6
ATOM 1761 CB VAL C 40 2.538 56.763 172.686 1.00 50.85 6
ATOM 1762 CGl VAL C 40 2.557 56.769 174.208 1.00 50.64 6
ATOM 1763 CG2 VAL C 40 3.333 57.925 172.128 1. 00 50.55 6
ATOM 1764 C VAL C 40 4.329 54.939 172.848 1.00 50.52 6
ATOM 1765 0 VAL C 40 5.417 55.490 172.651 1.00 50.47 8
ATOM 1766 N ASN C 41 4.198 53.894 173.656 1.00 50.07 7
ATOM 1767 CA ASN C 41 5.341 53.409 174.415 1.00 49.98 6
ATOM 1768 CB ASN C 41 5, 033 53.442 175.899 1.00 49.79 6
ATOM 1769 CG ASN C 41 4, 863 54.828 176.407 1.00 49.55 6
ATOM 1770 ODl ASN C 41 5.432 55.782 175.872 1.00 48.90 8
ATOM 1771 ND2 ASN C 41 4.065 54.962 177.452 1.00 50.65 7
ATOM 1772 C ASN C 41 5.892 52.037 174.048 1.00 50.14 6
ATOM 1773 0 ASN C 41 6.725 51.497 174.773 1.00 50.29 8
ATOM 1774 N ALA C 42 5.445 51.465 172.933 1.00 50.32 7
ATOM 1775 CA ALA C 42 6.014 50.200 172.442 1.00 50.41 6 ATOM 1776 CB ALA C 42 5.638 49.977 170.966 1.00 50.21 6
ATOM 1777 C ALA C 42 7.545 50.147 172.630 1.00 50.47 6
ATOM 1778 0 ALA C 42 8.247 51.123 172.333 1.00 50.77 8
ATOM 1779 N ASN C 43 8.041 49.022 173.149 1.00 50.10 7
ATOM 1780 CA ASN C 43 9.482 48.745 173.242 1.00 49.71 6
ATOM 1781 CB ASN C 43 9.781 47.955 174.519 1.00 49.84 6
ATOM 1782 CG ASN C 43 9.809 48.813 175.762 1.00 50.26 6
ATOM 1783 ODl ASN C 43 9.439 49.988 175.754 1.00 50.77 8
ATOM 1784 ND2 ASN C 43 10.248 48.216 176.855 1.00 51.24 7
ATOM 1785 C ASN C 43 9.972 47.902 172.073 1.00 49.26 6
ATOM 1786 O ASN C 43 9.260 47.013 171.627 1.00 49.60 8
ATOM 1787 N ASP C 44 11.185 48.140 171.586 1.00 48.62 7
ATOM 1788 CA ASP C 44 11.832 47.114 170.761 1.00 48.21 6
ATOM 1789 CB ASP C 44 12.734 47.698 169.669 1.00 48.44 6
ATOM 1790 CG ASP C 44 13.835 48.586 170.212 1.00 49.72 6
ATOM 1791 ODl ASP C 44 14.211 48.491 171.404 1.00 51.69 8
ATOM 1792 OD2 ASP C 44 14.342 49.393 169.416 1.00 51.27 8
ATOM 1793 C ASP C 44 12.579 46.146 171.678 1.00 47.54 6
ATOM 1794 0 ASP C 44 12.401 46.196 172.893 1.00 47.46 8
ATOM 1795 N ARG C 45 13.411 45.275 171.106 1.00 46.84 7
ATOM 1796 CA ARG C 45 14.098 44.232 171.876 1.00 46.16 6
ATOM 1797 CB ARG C 45 14.910 43.307 170.961 1.00 45.97 6
ATOM 1798 CG ARG C 45 14.248 43.071 169.581 1.00 47.44 6
ATOM 1799 CD ARG C 45 15.153 42.409 168.501 1.00 47.20 6
ATOM 1800 NE ARG C 45 16.577 42.752 168.638 1.00 48.72 7
ATOM 1801 CZ ARG C 45 17.141 43.922 168.308 1.00 48.46 6
ATOM 1802 NHl ARG C 45 16.420 44.932 167.804 1.00 48.74 7
ATOM 1803 NH2 ARG C 45 18.448 44.081 168.495 1.00 47.64 7
ATOM 1804 C ARG C 45 14.995 44.846 172.928 1.00 45.41 6
ATOM 1805 0 ARG C 45 15.149 44.278 174.001 1.00 45.32 8
ATOM 1806 N LYS C 46 15.566 46.014 172.626 1.00 44.92 7
ATOM 1807 CA LYS C 46 16.421 46.746 173.578 1.00 44.68 6
ATOM 1808 CB LYS C 46 17.748 47.177 172.952 1.00 44.75 6
ATOM 1809 CG LYS C 46 17.631 47.766 171.562 1.00 46.50 6
ATOM 1810 CD LYS C 46 18.134 46.785 170.516 1.00 49.83 6
ATOM 1811 CE LYS C 46 19.623 46.473 170.710 1.00 50.97 6
ATOM 1812 NZ LYS C 46 20.447 47.715 170.596 1.00 52.53 7
ATOM 1813 C LYS C 46 15.758 47.930 174.281 1.00 44.08 6
ATOM 1814 0 LYS C 46 16.408 48.874 174.671 1.00 44.20 8
ATOM 1815 N GLY C 47 14.458 47.864 174.468 1.00 43.74 7
ATOM 1816 CA GLY C 47 13.803 48.769 175.393 1.00 43.31 6
ATOM 1817 C GLY C 47 13.578 50.170 174.884 1.00 43.07 6
ATOM 1818 0 GLY C 47 13.007 50.996 175.598 1.00 43.23 8
ATOM 1819 N ASN C 48 14.023 50.439 173.660 1.00 42.69 7
ATOM 1820 CA ASN C 48 13.699 51.687 172.973 1.00 42.51 6
ATOM 1821 CB ASN C 48 14.237 51.656 171.566 1.00 42.50 6
ATOM 1822 CG ASN C 48 15.677 51.917 171.523 1.00 44.06 6
ATOM 1823 ODl ASN C 48 16.142 52.888 172.102 1.00 46.77 8
ATOM 1824 ND2 ASN C 48 16.420 51.048 170.861 1.00 45.28 7
ATOM 1825 C ASN C 48 12.227 51.894 172.825 1.00 42.06 6
ATOM 1826 0 ASN C 48 11.511 50.955 172.527 1.00 42.35 8
ATOM 1827 N THR C 49 11.772 53.125 173.011 1.00 41.66 7
ATOM 1828 CA THR C 49 10.414 53.483 172.640 1.00 41.37 6
ATOM 1829 CB THR C 49 9.635 54.175 173.777 1.00 41.48 6
ATOM 1830 OGl THR C 49 10.065 55.540 173.896 1.00 42.25 8
ATOM 1831 CG2 THR C 49 9.805 53.426 175.097 1.00 41.49 6 ATOM 1832 C THR C 49 10.491 54.419 171.450 1.00 41.10 6
ATOM 1833 0 THR C 49 11.548 54.980 171.178 1.00 41.19 8
ATOM 1834 N PRO C 50 9.364 54.630 170.753 1.00 40.93 7
ATOM 1835 CA PRO C 50 9.374 55.551 169.619 1.00 40.59 6
ATOM 1836 CB PRO C 50 7.880 55.812 169.378 1.00 40.88 6
ATOM 1837 CG PRO C 50 7.164 55.255 170.619 1.00 40.89 6
ATOM 1838 CD PRO C 50 8.011 54.100 170.997 1.00 41.10 6
ATOM 1839 C PRO C 50 10.077 56.863 169.965 1.00 40.26 6
ATOM 1840 0 PRO C 50 10.877 57.361 169.168 1.00 40.04 8
ATOM 1841 N LEU C 51 9.786 57.393 171.156 1.00 39.87 7
ATOM 1842 CA LEU C 51 10.417 58.623 171.619 1.00 39.69 6
ATOM 1843 CB LEU C 51 9.870 59.057 172.986 1.00 39.87 6
ATOM 1844 CG LEU C 51 10.407 60.401 173.504 1.00 39.23 6
ATOM 1845 CDl LEU C 51 9.846 61.554 172.699 1.00 38.27 6
ATOM 1846 CD2 LEU C 51 10.123 60.589 174.990 1.00 39.36 6
ATOM 1847 C LEU C 51 11.944 58.512 171.630 1.00 39.60 6
ATOM 1848 0 LEU C 51 12.637 59.418 171.147 1.00 39.45 8
ATOM 1849 N HIS C 52 12.463 57.405 172.154 1.00 39.46 7
ATOM 1850 CA HIS C 52 13.887 57.133 171.997 1.00 39.80 6
ATOM 1851 CB HIS C 52 14.246 55.715 172.419 1.00 39.79 6
ATOM 1852 CG HIS C 52 14.312 55.531 173.891 1.00 41.55 6
ATOM 1853 NDl HIS C 52 13.290 54.955 174.613 1.00 43.60 7
ATOM 1854 CEI HIS C 52 13.622 54.922 175.893 1.00 44.57 6
ATOM 1855 NE2 HIS C 52 14.819 55.468 176.028 1.00 44.57 7
ATOM 1856 CD2 HIS C 52 15.266 55.869 174.790 1.00 43.67 6
ATOM 1857 C HIS C 52 14.287 57.320 170.543 1.00 39.55 6
ATOM 1858 0 HIS C 52 15.045 58.229 170.207 1.00 39.55 8
ATOM 1859 N LEU C 53 13.761 56.466 169.675 1.00 39.33 7
ATOM 1860 CA LEU C 53 14.267 56.414 168.321 1.00 39.42 6
ATOM 1861 CB LEU C 53 13.504 55.413 167.475 1.00 39.20 6
ATOM 1862 CG LEU C 53 13.756 53.932 167.676 1.00 38.67 6
ATOM 1863 CDl LEU C 53 12.764 53.424 168.623 1.00 39.69 6
ATOM 1864 CD2 LEU C 53 13.567 53.218 166.372 1.00 39.89 6
ATOM 1865 C LEU C 53 14.174 57.786 167.696 1.00 39.86 6
ATOM 1866 0 LEU C 53 15.091 58.214 166.998 1.00 40.33 8
ATOM 1867 N ALA C 54 13.068 58.480 167.963 1.00 39.99 7
ATOM 1868 CA ALA C 54 12.844 59.798 167.391 1.00 40.11 6
ATOM 1869 CB ALA C 54 11.461 60.273 167.701 1.00 40.38 6
ATOM 1870 C ALA C 54 13.884 60.779 167.916 1.00 40.33 6
ATOM 1871 0 ALA C 54 14.332 61.665 167.179 1.00 40.23 8
ATOM 1872 N ALA C 55 14.269 60.610 169.187 1.00 40.49 7
ATOM 1873 CA ALA C 55 15.409 61.341 169.761 1.00 40.76 6
ATOM 1874 CB ALA C 55 15.544 61.055 171.245 1.00 40.30 6
ATOM 1875 C ALA C 55 16.695 60.944 169.027 1.00 41.05 6
ATOM 1876 0 ALA C 55 17.443 61.797 168.525 1.00 41.30 8
ATOM 1877 N ASP C 56 16.923 59.641 168.938 1.00 40.97 7
ATOM 1878 CA ASP C 56 18.115 59.131 168.319 1.00 41.27 6
ATOM 1879 CB ASP C 56 18.031 57.617 168.216 1.00 41.53 6
ATOM 1880 CG ASP C 56 19.385 56.977 168.127 1.00 42.42 6
ATOM 1881 ODl ASP C 56 19.959 56.818 167.028 1.00 42.45 8
ATOM 1882 0D2 ASP C 56 19.885 56.634 169.199 1.00 45.53 8
ATOM 1883 C ASP C 56 18.407 59.714 166.929 1.00 41.32 6
ATOM 1884 0 ASP C 56 19.572 59.880 166.565 1.00 41.35 8
ATOM 1885 N TYR C 57 17.374 60.008 166.148 1.00 41.31 7
ATOM 1886 CA TYR C 57 17.594 60.320 164.751 1.00 41.75 6
ATOM 1887 CB TYR C 57 16.847 59.320 163.884 1.00 41.69 6 ATOM 1888 CG TYR C 57 17.393 57.915 163.917 1.00 41.54 6
ATOM 1889 CDl TYR C 57 17.100 57.057 164.970 1.00 41.80 6
ATOM 1890 CEI TYR C 57 17.587 55.772 165.001 1.00 41.87 6
ATOM 1891 CZ TYR C 57 18.370 55.322 163.959 1.00 42.37 6
ATOM 1892 OH TYR C 57 18.869 54.046 163.989 1.00 42.86 8
ATOM 1893 CE2 TYR C 57 18.665 56.144 162.897 1.00 41.95 6
ATOM 1894 CD2 TYR C 57 18.171 57.432 162.882 1.00 41.62 6
ATOM 1895 C TYR C 57 17.119 61.717 164.433 1.00 42.35 6
ATOM 1896 O TYR C 57 16.438 61.933 163.426 1.00 42.49 8
ATOM 1897 N ASP C 58 17.524 62.683 165.252 1.00 42.97 7
ATOM 1898 CA ASP C 58 16.711 63.901 165.447 1.00 43.79 6
ATOM 1899 CB ASP C 58 17.505 65.184 165.822 1.00 43.91 6
ATOM 1900 CG ASP C 58 18.422 65.676 164.743 1.00 43.35 6
ATOM 1901 ODl ASP C 58 18.631 64.954 163.766 1.00 43.95 8
ATOM 1902 0D2 ASP C 58 18.966 66.792 164.902 1.00 42.91 8
ATOM 1903 C ASP C 58 15.562 64.167 164.470 1.00 44.21 6
ATOM 1904 O ASP C 58 15.736 64.651 163.373 1.00 43.85 8
ATOM 1905 N HIS C 59 14.377 63.799 164.923 1.00 45.34 7
ATOM 1906 CA HIS C 59 13.156 64.100 164.244 1.00 46.35 6
ATOM 1907 CB HIS C 59 12.435 62.809 163.885 1.00 46.42 6
ATOM 1908 CG HIS C 59 13.191 61.955 162.915 1.00 47.08 6
ATOM 1909 NDl HIS C 59 13.490 62.370 161.634 1.00 47.74 7
ATOM 1910 CEI HIS C 59 14.156 61.415 161.012 1.00 47.94 6
ATOM 1911 NE2 HIS C 59 14.297 60.395 161.840 1.00 47.52 7
ATOM 1912 CD2 HIS C 59 13.702 60.707 163.036 1.00 47.53 6
ATOM 1913 C HIS C 59 12.350 64.948 165.201 1.00 46.86 6
ATOM 1914 0 HIS C 59 11.447 64.464 165.867 1.00 47.16 8
ATOM 1915 N LEU C 60 12.711 66.221 165.269 1.00 47.53 7
ATOM 1916 CA LEU C 60 12.121 67.163 166.206 1.00 48.37 6
ATOM 1917 CB LEU C 60 12.542 68.582 165.803 1.00 48.14 6
ATOM 1918 CG LEU C 60 12.455 69.824 166.697 1.00 47.18 6
ATOM 1919 CDl LEU C 60 11.120 69.957 167.439 1.00 47.43 6
ATOM 1920 CD2 LEU C 60 13.598 69.867 167.669 1.00 46.68 6
ATOM 1921 C LEU C 60 10.588 67.061 166.273 1.00 49.28 6
ATOM 1922 0 LEU C 60 10.006 66.900 167.346 1.00 49.51 8
ATOM 1923 N GLU C 61 9.943 67.163 165.122 1.00 50.22 7
ATOM 1924 CA GLU C 61 8.487 67.168 165.047 1.00 51.57 6
ATOM 1925 CB GLU C 61 8.009 67.441 163.600 1.00 52.19 6
ATOM 1926 CG GLU C 61 8.695 66.590 162.476 1.00 56.17 6
ATOM 1927 CD GLU C 61 10.241 66.686 162.433 1.00 60.23 6
ATOM 1928 OEl GLU C 61 10.920 65.656 162.655 1.00 61.20 8
ATOM 1929 OE2 GLU C 61 10.775 67.787 162.176 1.00 61.91 8
ATOM 1930 C GLU C 61 7.906 65.874 165.619 1.00 51.11 6
ATOM 1931 0 GLU C 61 7.076 65.913 166.533 1.00 51.38 8
ATOM 1932 N ILE C 62 8.377 64.741 165.104 1.00 50.55 7
ATOM 1933 CA ILE C 62 7.938 63.430 165.563 1.00 50.11 6
ATOM 1934 CB ILE C 62 8.709 62.290 164.837 1.00 50.17 6
ATOM 1935 CGl ILE C 62 8.206 62.175 163.394 1.00 50.18 6
ATOM 1936 CD ILE C 62 9.263 61.858 162.399 1.00 49.48 6
ATOM 1937 CG2 ILE C 62 8.540 60.943 165.537 1.00 49.42 6
ATOM 1938 C ILE C 62 8.036 63.347 167.080 1.00 50.05 6
ATOM 1939 O ILE C 62 7.117 62.864 167.725 1.00 50.34 8
ATOM 1940 N VAL C 63 9.125 63.863 167.643 1.00 49.92 7
ATOM 1941 CA VAL C 63 9.305 63.931 169.095 1.00 49.85 6
ATOM 1942 CB VAL C 63 10.677 64.575 169.468 1.00 49.52 6
ATOM 1943 CGl VAL C 63 10.713 65.024 170.909 1.00 49.03 6 ATOM 1944 CG2 VAL C 63 11.786 63.608 169.208 1.00 48.80 6
ATOM 1945 C VAL C 63 8.119 64.671 169.743 1.00 50.52 6
ATOM 1946 O VAL C 63 7.530 64.189 170.723 1.00 50.37 8
ATOM 1947 N GLU C 64 7.752 65.816 169.171 1.00 51.25 7
ATOM 1948 CA GLU C 64 6.645 66.602 169.701 1.00 52.42 6
ATOM 1949 CB GLU C 64 6.544 67.935 168.975 1.00 52.78 6
ATOM 1950 CG GLU C 64 7.551 68.957 169.447 1.00 55.48 6
ATOM 1951 CD GLU C 64 7.202 70.364 168.980 1.00 59.27 6
ATOM 1952 OEl GLU C 64 7.506 70.711 167.809 1.00 60.55 8
ATOM 1953 0E2 GLU C 64 6.625 71.126 169.791 1.00 60.61 8
ATOM 1954 C GLU C 64 5.315 65.857 169.614 1.00 52.49 6
ATOM 1955 O GLU C 64 4.544 65.821 170.581 1.00 52.52 8
ATOM 1956 N VAL C 65 5.064 65.264 168.448 1.00 52.51 7
ATOM 1957 CA VAL C 65 3.887 64.431 168.204 1.00 52.43 6
ATOM 1958 CB VAL C 65 3.974 63.766 166.814 1.00 52.30 6
ATOM 1959 CGl VAL C 65 2.683 63.040 166.475 1.00 52.45 6
ATOM 1960 CG2 VAL C 65 4.292 64.798 165.760 1.00 52.20 6
ATOM 1961 C VAL C 65 3.739 63.333 169.256 1.00 52.50 6
ATOM 1962 O VAL C 65 2.639 63.079 169.753 1.00 52.43 8
ATOM 1963 N LEU C 66 4.858 62.688 169.577 1.00 52.62 7
ATOM 1964 CA LEU C 66 4.887 61.605 170.549 1.00 53.09 6
ATOM 1965 CB LEU C 66 6.240 60.897 170.535 1.00 53.01 6
ATOM 1966 CG LEU C 66 6.584 60.033 169.313 1.00 53.28 6
ATOM 1967 CDl LEU C 66 8.042 59.561 169.363 1.00 53.18 6
ATOM 1968 CD2 LEU C 66 5.627 58.853 169.152 1.00 52.89 6
ATOM 1969 C LEU C 66 4.584 62.101 171.956 1.00 53.60 6
ATOM 1970 O LEU C 66 3.863 61.442 172.722 1.00 53.72 8
ATOM 1971 N LEU C 67 5.136 63.264 172.291 1.00 53.88 7
ATOM 1972 CA LEU C 67 4.866 63.898 173.573 1.00 53.90 6
ATOM 1973 CB LEU C 67 5.821 65.058 173.784 1.00 53.68 6
ATOM 1974 CG LEU C 67 7.252 64.554 173.916 1.00 53.65 6
ATOM 1975 CDl LEU C 67 8.249 65.684 173.740 1.00 54.14 6
ATOM 1976 CD2 LEU C 67 7.444 63.849 175.248 1.00 53.33 6
ATOM 1977 C LEU C 67 3.414 64.361 173.681 1.00 53.98 6
ATOM 1978 O LEU C 67 2.801 64.239 174.740 1.00 54.09 8
ATOM 1979 N LYS C 68 2.866 64.875 172.583 1.00 53.92 7
ATOM 1980 CA LYS C 68 1.463 65.256 172.543 1.00 53.97 6
ATOM 1981 CB LYS C 68 1.088 65.955 171.232 1.00 54.03 6
ATOM 1982 CG LYS C 68 1.240 67.471 171.258 1.00 54.50 6
ATOM 1983 CD LYS C 68 0.865 68.082 169.910 1.00 54.47 6
ATOM 1984 CE LYS C 68 1.161 69.584 169.846 1.00 55.14 6
ATOM 1985 NZ LYS C 68 2.534 69.914 169.359 1.00 54.89 7
ATOM 1986 C LYS C 68 0.569 64.052 172.756 1.00 53.51 6
ATOM 1987 0 LYS C 68 -0.495 64.194 173.321 1.00 53.64 8
ATOM 1988 N HIS C 69 0.990 62.871 172.312 1.00 53.14 7
ATOM 1989 CA HIS C 69 0.193 61.652 172.502 1.00 52.98 6
ATOM 1990 CB HIS C 69 0.344 60.706 171.301 1.00 52.96 6
ATOM 1991 CG HIS C 69 -0.534 61.052 170.133 1.00 53.77 6
ATOM 1992 NDl HIS C 69 -1.806 60.537 169.976 1.00 54.15 7
ATOM 1993 CEI HIS C 69 -2.341 61.012 168.864 1.00 53.78 6
ATOM 1994 NE2 HIS C 69 -1.457 61.804 168.284 1.00 54.43 7
ATOM 1995 CD2 HIS C 69 -0.316 61.843 169.054 1.00 54.46 6
ATOM 1996 C HIS C 69 0.543 60.940 173.821 1.00 52.86 6
ATOM 1997 0 HIS C 69 0.061 59.835 174.103 1.00 52.83 8
ATOM 1998 N GLY C 70 1.389 61.587 174.618 1.00 52.62 7
ATOM 1999 CA GLY C 70 1.705 61.132 175.960 1.00 52.17 6 ATOM 2000 C GLY C 70 2.706 60.000 176.022 00 52.07
ATOM 2001 O GLY C 70 2.515 59.064 176.796 00 52.16
ATOM 2002 N ALA C 71 3.768 60.070 175.214 00 51.85 7
ATOM 2003 CA ALA C 71 4.919 59.175 175.378 00 51.40 6
ATOM 2004 CB ALA C 71 5.917 59.372 174.254 00 51.45 6
ATOM 2005 C ALA C 71 5.577 59.476 176.716 00 51.14 6
ATOM 2006 O ALA C 71 5.672 60.639 177.103 00 51.39
ATOM 2007 N ASP C 72 6.008 58.436 177.428 00 50.69 7
ATOM 2008 CA ASP C 72 6.809 58.612 178.652 00 50.23 6
ATOM 2009 CB ASP C 72 7.092 57.264 179.335 00 50.46 6
ATOM 2010 CG ASP C 72 7.960 57.394 180.593 00 51.08
ATOM 2011 ODl ASP C 72 7.967 58.462 181.256 00 51.83
ATOM 2012 OD2 ASP C 72 8.626 56.393 180.932 00 52.53
ATOM 2013 C ASP C 72 8.120 59.284 178.289 1.00 49.60
ATOM 2014 O ASP C 72 8.918 58.726 177.537 1.00 49.62
ATOM 2015 N VAL C 73 8.325 60.484 178.820 1 00 48.85 7
ATOM 2016 CA VAL C 73 9.497 61.290 178.504 1 00 48.29 6
ATOM 2017 CB VAL C 73 9.284 62.768 178.932 1.00 48.25 6
ATOM 2018 CGl VAL C 73 8.763 62.854 180.348 1.00 48.02 6
ATOM 2019 CG2 VAL C 73 10.551 63.580 178.783 1.00 47.81 6
ATOM 2020 C VAL C 73 10.769 60.708 179.117 1.00 48.13 6
ATOM 2021 O VAL C 73 11.842 60.843 178.562 00 48.26 8
ATOM 2022 N ASN C 74 10.639 60.041 180.250 1.00 47.86 7
ATOM 2023 CA ASN C 74 11.794 59.533 180.950 1.00 47.63 6
ATOM 2024 CB ASN C 74 11.687 59.891 182.428 1 ,00 47.90 6
ATOM 2025 CG ASN C 74 11.536 61.366 182.652 1 ,00 47.99 6
ATOM 2026 ODl ASN C 74 12.484 62.137 182.466 1.00 48.86 8
ATOM 2027 ND2 ASN C 74 10.341 61.776 183.054 1.00 47.63 7
ATOM 2028 C ASN C 74 11.935 58.034 180.799 1.00 47.36 6
ATOM 2029 O ASN C 74 12.514 57.367 181.656 1.00 47.46 8
ATOM 2030 N ALA C 75 11.398 57.487 179.723 1.00 46.92 7
ATOM 2031 CA ALA C 75 11.521 56.056 179.515 1.00 46.93 6
ATOM 2032 CB ALA C 75 10.782 55.633 178.265 1.00 46.96 6
ATOM 2033 C ALA C 75 13.011 55.686 179.434 00 47.10 6
ATOM 2034 O ALA C 75 13.784 56.348 178.737 00 47.54 8
ATOM 2035 N HIS C 76 13.428 54.670 180.182 1.00 46.78 7
ATOM 2036 CA HIS C 76 14.778 54.157 180.049 ,00 46.55 6
ATOM 2037 CB HIS C 76 15.323 53.684 181.393 ,00 47.13 6
ATOM 2038 CG HIS C 76 15.153 54.671 182.521 ,00 50.18 6
ATOM 2039 NDl HIS C 76 16.207 55.395 183.051 ,00 52.42 7
ATOM 2040 CEI HIS C 76 15.769 56.154 184.043 1.00 51.73 6
ATOM 2041 NE2 HIS C 76 14.471 55.947 184.183 1.00 52.15 7
ATOM 2042 CD2 HIS C 76 14.063 55.014 183.255 1 ,00 51.95 6
ATOM 2043 C HIS C 76 14.728 52.997 179.061 1 ,00 46.10 6
ATOM 2044 O HIS C 76 13.739 52.266 178.994 1 ,00 45.88
ATOM 2045 N ASP C 77 15.778 52.838 178.265 1 ,00 45.73 7
ATOM 2046 CA ASP C 77 15.915 51.638 177.448 1.00 45.27 6
ATOM 2047 CB ASP C 77 16.885 51.884 176.299 1.00 45.75 6
ATOM 2048 CG ASP C 77 18.305 52.212 176.782 1 ,00 48.00 6
ATOM 2049 ODl ASP C 77 18.547 52.181 178.006 1 ,00 49.64
ATOM 2050 OD2 ASP C 77 19.187 52.499 175.936 1 ,00 51.11
ATOM 2051 C ASP C 77 16.426 50.560 178.392 1 ,00 44.35
ATOM 2052 O ASP C 77 16.435 50.769 179.600 1.00 43.90
ATOM 2053 N ASN C 78 16.880 49.432 177.852 ,00 43.82 7
ATOM 2054 CA ASN C 78 17.356 48.320 178.684 ,00 43.36 6
ATOM 2055 CB ASN C 78 17.477 47.028 177.872 1.00 43.33 6 ATOM 2056 CG ASN C 78 16.122 46.486 177.390 1.00 45.05 6
ATOM 2057 ODl ASN C 78 15.049 46.672 178.005 1.00 45.62 8
ATOM 2058 ND2 ASN C 78 16.181 45.775 176.285 1.00 47.40 7
ATOM 2059 C ASN C 78 18.677 48.590 179.377 1.00 42.53 6
ATOM 2060 O ASN C 78 19.008 47.940 180.357 1.00 42.61 8
ATOM 2061 N ASP C 79 19.434 49.540 178.850 1.00 41.94 7
ATOM 2062 CA ASP C 79 20.707 49.933 179.436 1.00 41.54 6
ATOM 2063 CB ASP C 79 21.695 50.269 178.339 1.00 41.73 6
ATOM 2064 CG ASP C 79 22.573 49.110 177.989 1.00 43.28 6
ATOM 2065 ODl ASP C 79 22.293 47.957 178.428 1.00 43.10 8
ATOM 2066 OD2 ASP C 79 23.559 49.362 177.267 1.00 45.59 8
ATOM 2067 C ASP C 79 20.553 51.147 180.307 1.00 41.06 6
ATOM 2068 O ASP C 79 21.523 51.663 180.842 1.00 41.01 8
ATOM 2069 N GLY C 80 19.325 51.637 180.406 1.00 40.69 7
ATOM 2070 CA GLY C 80 19.030 52.793 181.239 1.00 39.86 6
ATOM 2071 C GLY C 80 19.076 54.170 180.603 1.00 39.22 6
ATOM 2072 O GLY C 80 18.754 55.141 181.274 1.00 39.39 8
ATOM 2073 N SER C 81 19.467 54.276 179.332 1.00 38.75 7
ATOM 2074 CA SER C 81 19.492 55.579 178.646 1.00 38.28 6
ATOM 2075 CB SER C 81 20.259 55.510 177.323 1.00 37.96 6
ATOM 2076 OG SER C 81 21.379 54.637 177.408 1.00 38.47 8
ATOM 2077 C SER C 81 18.069 56.060 178.392 1.00 38.05 6
ATOM 2078 O SER C 81 17.218 55.303 177.896 1.00 37.96 8
ATOM 2079 N THR C 82 17.797 57.310 178.755 1.00 37.83 7
ATOM 2080 CA THR C 82 16.532 57.960 178.383 1.00 37.48 6
ATOM 2081 CB THR C 82 16.167 58.998 179.386 1.00 37.32 6
ATOM 2082 OGl THR C 82 17.237 59.947 179.439 1.00 37.28 8
ATOM 2083 CG2 THR C 82 15.924 58.368 180.752 1.00 36.78 6
ATOM 2084 C THR C 82 16.705 58.704 177.070 1.00 37.70 6
ATOM 2085 O THR C 82 17.828 58.966 176.654 1.00 38.11 8
ATOM 2086 N PRO C 83 15.609 59.070 176.405 1.00 37.69 7
ATOM 2087 CA PRO C 83 15.815 59.867 175.195 1.00 37.86 6
ATOM 2088 CB PRO C 83 14.396 60.275 174.814 1.00 37.73 6
ATOM 2089 CG PRO C 83 13.573 59.153 175.293 1.00 37.94 6
ATOM 2090 CD PRO C 83 14.184 58.798 176.628 1.00 37.75 6
ATOM 2091 C PRO C 83 16.742 61.100 175.403 1.00 37.90 6
ATOM 2092 O PRO C 83 17.591 61.400 174.535 1.00 37.89 8
ATOM 2093 N LEU C 84 16.620 61.778 176.542 1.00 37.60 7
ATOM 2094 CA LEU C 84 17.541 62.866 176.845 1.00 37.49 6
ATOM 2095 CB LEU C 84 17.316 63.433 178.247 1.00 37.61 6
ATOM 2096 CG LEU C 84 17.897 64.826 178.492 1.00 37.02 6
ATOM 2097 CDl LEU C 84 17.428 65.798 177.435 1.00 35.89 6
ATOM 2098 CD2 LEU C 84 17.490 65.309 179.872 1.00 38.20 6
ATOM 2099 C LEU C 84 18.998 62.448 176.661 1.00 37.56 6
ATOM 2100 O LEU C 84 19.745 63.154 175.963 1.00 37.67 8
ATOM 2101 N HIS C 85 19.395 61.312 177.254 1.00 37.28 7
ATOM 2102 CA HIS C 85 20.743 60.755 177.008 1.00 37.48 6
ATOM 2103 CB HIS C 85 20.898 59.343 177.594 1.00 38.12 6
ATOM 2104 CG HIS C 85 20.914 59.315 179.085 1.00 40.16 6
ATOM 2105 NDl HIS C 85 19.791 59.568 179.843 1.00 42.29 7
ATOM 2106 CEI HIS C 85 20.105 59.492 181.125 1.00 43.32 6
ATOM 2107 NE2 HIS C 85 21.388 59.191 181.225 1.00 43.15 7
ATOM 2108 CD2 HIS C 85 21.918 59.078 179.962 1.00 41.88 6
ATOM 2109 C HIS C 85 21.083 60.728 175.517 1.00 36.69 6
ATOM 2110 O HIS C 85 22.068 61.328 175.083 1.00 35.87 8
ATOM 2111 N LEU C 86 20.247 60.053 174.737 1.00 36.44 7 ATOM 2112 CA LEU C 86 20.531 59.913 173.332 .00 36.66
ATOM 2113 CB LEU C 86 19.449 59.138 172.587 .00 36.73
ATOM 2114 CG LEU C 86 19.408 57.605 172.678 ,00 36.84
ATOM 2115 CDl LEU C 86 20.722 57.006 173.202 .00 36.68
ATOM 2116 CD2 LEU C 86 18.274 57.188 173.578 1.00 37.43
ATOM 2117 C LEU C 86 20.722 61.262 172.696 00 36.94
ATOM 2118 0 LEU C 86 21.746 61.502 172.047 00 37.14
ATOM 2119 N ALA C 87 19.752 62.152 172.894 1.00 37.20 7
ATOM 2120 CA ALA C 87 19.821 63.482 172.288 .00 37.51 6
ATOM 2121 CB ALA C 87 18.668 64.344 172.745 .00 37.76
ATOM 2122 C ALA C 87 21.150 64.126 172.643 ,00 37.57
ATOM 2123 0 ALA C 87 21.850 64.636 171.760 1.00 37.43
ATOM 2124 N ALA C 88 21.498 64.051 173.933 .00 37.46 7
ATOM 2125 CA ALA C 88 22.762 64.571 174.438 .00 37.43 6
ATOM 2126 CB ALA C 88 22.902 64.283 175.905 1.00 37.42 6
ATOM 2127 C ALA C 88 23.946 63.995 173.674 00 37.29
ATOM 2128 0 ALA C 88 24.728 64.750 173.093 00 37.65
ATOM 2129 N LEU C 89 24.066 62.671 173.656 00 36.76 7
ATOM 2130 CA LEU C 89 25.218 62.039 173.050 1.00 36.55 6
ATOM 2131 CB LEU C 89 25.140 60.541 173.229 ,00 36.40 6
ATOM 2132 CG LEU C 89 25.989 59.583 172.405 .00 36.40 6
ATOM 2133 CDl LEU C 89 27.454 59.833 172.643 .00 36.83 6
ATOM 2134 CD2 LEU C 89 25.633 58.144 172.761 1.00 36.12 6
ATOM 2135 C LEU C 89 25.373 62.418 171.586 .00 37.28 6
ATOM 2136 0 LEU C 89 26.504 62.574 171.114 .00 37.43
ATOM 2137 N PHE C 90 24.264 62.596 170.864 .00 37.79
ATOM 2138 CA PHE C 90 24.385 62.963 169.444 .00 38.27
ATOM 2139 CB PHE C 90 23.380 62.250 168.538 .00 38.44
ATOM 2140 CG PHE C 90 23.384 60.765 168.677 .00 39.28
ATOM 2141 CDl PHE C 90 22.235 60.096 169.066 .00 39.62
ATOM 2142 CEI PHE C 90 22.227 58.726 169.210 .00 38.96
ATOM 2143 CZ PHE C 90 23.369 58.008 168.974 .00 38.72
ATOM 2144 CE2 PHE C 90 24.534 58.667 168.598 .00 39.29
ATOM 2145 CD2 PHE C 90 24.538 60.035 168.453 .00 39.56
ATOM 2146 C PHE C 90 24.282 64.438 169.185 .00 38.58
ATOM 2147 0 PHE C 90 24.317 64.843 168.026 .00 39.24
ATOM 2148 N GLY C 91 24.138 65.241 170.232 .00 38.69 7
ATOM 2149 CA GLY C 91 24.145 66.697 170.075 .00 39.30 6
ATOM 2150 C GLY C 91 22.935 67.331 169.402 .00 39.82 6
ATOM 2151 0 GLY C 91 23.028 68.406 168.813 .00 39.43 8
ATOM 2152 N HIS C 92 21.796 66.666 169.514 .00 40.82 7
ATOM 2153 CA HIS C 92 20.544 67.177 168.996 .00 42.02 6
ATOM 2154 CB HIS C 92 19.609 66.011 168.746 ,00 42.01 6
ATOM 2155 CG HIS C 92 20.167 65.003 167.796 .00 42.13 6
ATOM 2156 NDl HIS C 92 19.855 63.664 167.861 .00 42.74 7
ATOM 2157 CEI HIS C 92 20.490 63.021 166.897 .00 42.66 6
ATOM 2158 NE2 HIS C 92 21.209 63.894 166.215 .00 41.68 7
ATOM 2159 CD2 HIS C 92 21.029 65.139 166.760 .00 41.95 6
ATOM 2160 C HIS C 92 19.920 68.200 169.945 .00 42.92 6
ATOM 2161 0 HIS C 92 18.990 67.900 170.714 .00 42.85
ATOM 2162 N LEU C 93 20.434 69.424 169.875 .00 43.91 7
ATOM 2163 CA LEU C 93 20.141 70.408 170.912 .00 45.07 6
ATOM 2164 CB LEU C 93 20.897 71.727 170.700 .00 45.13 6
ATOM 2165 CG LEU C 93 22.425 71.701 170.509 1.00 46.93 6
ATOM 2166 CDl LEU C 93 23.158 70.530 171.249 1.00 47.92 6
ATOM 2167 CD2 LEU C 93 22.805 71.706 169.024 1.00 48.28 6 ATOM 2168 C LBϋ C 93 18.668 70.656 170.980 1.00 45.47 6
ATOM 2169 0 LEU C 93 18.025 70.358 171.969 1.00 45.32 8
ATOM 2170 N GLU C 94 18.138 71.177 169.891 1.00 46.32 7
ATOM 2171 CA GLU C 94 16.739 71.515 169.819 1.00 47.42 6
ATOM 2172 CB GLU C 94 16.304 71.933 168.390 1.00 47.58 6
ATOM 2173 CG GLU C 94 16.888 71.113 167.234 1.00 50.17 6
ATOM 2174 CD GLU C 94 18.385 70.793 167.392 1.00 53.61 6
ATOM 2175 OEl GLU C 94 18.720 69.646 167.809 1.00 54.04 8
ATOM 2176 0E2 GLU C 94 19.214 71.694 167.108 1.00 54.33 8
ATOM 2177 C GLU C 94 15.896 70.408 170.457 1.00 47.47 6
ATOM 2178 O GLU C 94 14.964 70.715 171.197 1.00 48.02 8
ATOM 2179 N ILE C 95 16.254 69.140 170.261 1.00 47.32 7
ATOM 2180 CA ILE C 95 15.453 68.071 170.874 1.00 47.28 6
ATOM 2181 CB ILE C 95 15.757 66.709 170.272 1.00 47.59 6
ATOM 2182 CGl ILE C 95 15.358 66.718 168.785 1.00 48.24 6
ATOM 2183 CD ILE C 95 14.957 65.358 168.229 1.00 50.27 6
ATOM 2184 CG2 ILE C 95 15.087 65.587 171.120 1.00 46.89 6
ATOM 2185 C ILE C 95 15.613 68.023 172.388 1.00 47.24 6
ATOM 2186 0 ILE C 95 14.632 67.980 173.149 1.00 47.07 8
ATOM 2187 N VAL C 96 16.865 68.040 172.811 1.00 47.19 7
ATOM 2188 CA VAL C 96 17.189 68.213 174.202 1.00 47.32 6
ATOM 2189 CB VAL C 96 18.639 68.677 174.307 1.00 47.43 6
ATOM 2190 CGl VAL C 96 18.906 69.317 175.651 1.00 47.63 6
ATOM 2191 CG2 VAL C 96 19.589 67.505 174.019 1.00 47.60 6
ATOM 2192 C VAL C 96 16.244 69.242 174.843 1.00 47.32 6
ATOM 2193 O VAL C 96 15.580 68.964 175.838 1.00 47.33 8
ATOM 2194 N GLU C 97 16.160 70.417 174.241 1.00 47.32 7
ATOM 2195 CA GLU C 97 15.344 71.476 174.796 1.00 47.47 6
ATOM 2196 CB GLU C 97 15.454 72.731 173.964 1.00 47.78 6
ATOM 2197 CG GLU C 97 16.871 73.053 173.589 1.00 49.63 6
ATOM 2198 CD GLU C 97 17.003 74.461 173.093 1.00 52.37 6
ATOM 2199 OEl GLU C 97 16.365 74.791 172.061 1.00 53.22 8
ATOM 2200 0E2 GLU C 97 17.737 75.238 173.747 1.00 53.08 8
ATOM 2201 C GLU C 97 13.894 71.074 174.910 1.00 47.03 6
ATOM 2202 0 GLU C 97 13.359 71.057 176.008 1.00 47.28 8
ATOM 2203 N VAL C 98 13.258 70.739 173.793 1.00 46.46 7
ATOM 2204 CA VAL C 98 11.863 70.281 173.844 1.00 46.18 6
ATOM 2205 CB VAL C 98 11.257 69.922 172.434 1.00 46.11 6
ATOM 2206 CGl VAL C 98 12.262 70.097 171.333 1.00 46.16 6
ATOM 2207 CG2 VAL C 98 10.622 68.519 172.408 1.00 45.61 6
ATOM 2208 C VAL C 98 11.620 69.166 174.882 1.00 46.03 6
ATOM 2209 0 VAL C 98 10.575 69.159 175.564 1.00 46.08 8
ATOM 2210 N LEU C 99 12.583 68.251 175.014 1.00 45.44 7
ATOM 2211 CA LEU C 99 12.486 67.196 176.014 1.00 44.79 6
ATOM 2212 CB LEU C 99 13.623 66.204 175.860 1.00 44.41 6
ATOM 2213 CG LEU C 99 13.490 65.159 174.761 1.00 43.50 6
ATOM 2214 CDl LEU C 99 14.792 64.418 174.654 1.00 43.91 6
ATOM 2215 CD2 LEU C 99 12.369 64.187 175.061 1.00 42.42 6
ATOM 2216 C LEU C 99 12.467 67.774 177.422 1.00 44.79 6
ATOM 2217 0 LEU C 99 11.629 67.394 178.244 1.00 44.36 8
ATOM 2218 N LEU C 100 13.380 68.708 177.684 1.00 44.88 7
ATOM 2219 CA LEU C 100 13.417 69.424 178.953 1.00 45.06 6
ATOM 2220 CB LEU C 100 14.531 70.459 178.946 1.00 44.71 6
ATOM 2221 CG LEU C 100 15.903 69.824 178.840 1.00 43.97 6
ATOM 2222 CDl LEU C 100 16.958 70.863 178.570 1.00 43.81 6
ATOM 2223 CD2 LEU C 100 16.195 69.073 180.109 1.00 43.51 6 ATOM 2224 C LEU C 100 12.099 70.113 179.206 1.00 45.56
ATOM 2225 0 LEU C 100 11.518 69.970 180.277 1.00 44.98 8
ATOM 2226 N LYS C 101 11.642 70.851 178.191 1.00 46.67 7
ATOM 2227 CA LYS C 101 10.376 71.586 178.223 1.00 48.03 6
ATOM 2228 CB LYS C 101 10.035 72.188 176.844 1.00 47.97 6
ATOM 2229 CG LYS C 101 8.770 73.083 176.818 1.00 48.91 6
ATOM 2230 CD LYS C 101 8.161 73.219 175.416 1.00 49.16 6
ATOM 2231 CE LYS C 101 8.738 74.396 174.640 1.00 51.06 6
ATOM 2232 NZ LYS C 101 8.521 74.238 173.174 1.00 51.85 7
ATOM 2233 C LYS C 101 9.256 70.669 178.683 1.00 48.34 6
ATOM 2234 0 LYS C 101 8.460 71.038 179.533 1.00 48.37 8
ATOM 2235 N HIS C 102 9.211 69.467 178.121 1.00 49.10 7
ATOM 2236 CA HIS C 102 8.221 68.474 178.518 1.00 49.76 6
ATOM 2237 CB HIS C 102 7.949 67.504 177.364 1.00 50.06 6
ATOM 2238 CG HIS C 102 7.093 68.069 176.277 1.00 50.98 6
ATOM 2239 NDl HIS C 102 5.836 67.577 175.990 1.00 51.82 7
ATOM 2240 CEI HIS C 102 5.322 68.253 174.980 1.00 52.14 6
ATOM 2241 NE2 HIS C 102 6.199 69.165 174.602 1.00 52.60 7
ATOM 2242 CD2 HIS C 102 7.317 69.070 175.395 1.00 51.82 6
ATOM 2243 C HIS C 102 8.653 67.694 179.765 1.00 49.77 6
ATOM 2244 0 HIS C 102 8.142 66.603 180.022 1.00 49.90 8
ATOM 2245 N GLY C 103 9.608 68.242 180.516 1.00 49.76 7
ATOM 2246 CA GLY C 103 9.953 67.728 181.839 1.00 49.69 6
ATOM 2247 C GLY C 103 10.832 66.494 181.890 1.00 49.55 6
ATOM 2248 0 GLY C 103 10.753 65.719 182.844 1.00 49.94 8
ATOM 2249 N ALA C 104 11.670 66.293 180.880 1.00 49.09 7
ATOM 2250 CA ALA C 104 12.710 65.275 180.983 1.00 48.39 6
ATOM 2251 CB ALA C 104 13.644 65.325 179.774 1.00 48.65 6
ATOM 2252 C ALA C 104 13.489 65.504 182.276 1.00 47.83 6
ATOM 2253 0 ALA C 104 13.787 66.640 182.645 1.00 47.75 8
ATOM 2254 N ASP C 105 13.786 64.424 182.976 1.00 47.34 7
ATOM 2255 CA ASP C 105 14.571 64.512 184.181 1.00 47.34 6
ATOM 2256 CB ASP C 105 14.344 63.246 185.000 1.00 47.94 6
ATOM 2257 CG ASP C 105 14.988 63.300 186.374 1.00 49.66 6
ATOM 2258 ODl ASP C 105 15.249 64.414 186.894 1.00 52.12 8
ATOM 2259 0D2 ASP C 105 15.219 62.204 186.939 1.00 51.07 8
ATOM 2260 C ASP C 105 16.042 64.658 183.803 1.00 46.72 6
ATOM 2261 0 ASP C 105 16.634 63.731 183.271 1.00 46.93 8
ATOM 2262 N VAL C 106 16.624 65.824 184.059 1.00 45.97 7
ATOM 2263 CA VAL C 106 18.026 66.081 183.721 1.00 45.49 6
ATOM 2264 CB VAL C 106 18.409 67.567 183.938 1.00 45.52 6
ATOM 2265 CGl VAL C 106 17.467 68.211 184.952 1.00 46.22 6
ATOM 2266 CG2 VAL C 106 19.879 67.735 184.373 1.00 44.70 6
ATOM 2267 C VAL C 106 18.923 65.178 184.554 1.00 45.38 6
ATOM 2268 0 VAL C 106 20.049 64.828 184.147 1.00 46.06 8
ATOM 2269 N ASN C 107 18.411 64.772 185.707 1.00 44.49 7
ATOM 2270 CA ASN C 107 19.209 63.989 186.635 1.00 43.88 6
ATOM 2271 CB ASN C 107 18.873 64.376 188.060 1.00 43.93 6
ATOM 2272 CG ASN C 107 19.599 65.601 188.465 1.00 44.00 6
ATOM 2273 ODl ASN C 107 20.613 65.960 187.840 1.00 43.75 8
ATOM 2274 ND2 ASN C 107 19.095 66.284 189.484 1.00 43.61 7
ATOM 2275 C ASN C 107 19.138 62.498 186.457 1.00 43.34 6
ATOM 2276 0 ASN C 107 19.879 61.745 187.096 1.00 43.48 8
ATOM 2277 N ALA C 108 18.242 62.069 185.586 1.00 42.63 7
ATOM 2278 CA ALA C 108 18.106 60.659 185.321 1.00 42.04 6
ATOM 2279 CB ALA C 108 16.959 60.410 184.365 1.00 42.24 6 ATOM 2280 C ALA C 108 19.431 60.101 184.785 1.00 41.75 6
ATOM 2281 O ALA C 108 20.115 60.735 183.940 1.00 41.66 8
ATOM 2282 N GLN C 109 19.794 58.932 185.314 1.00 41.20 7
ATOM 2283 CA GLN C 109 21.062 58.275 184.975 1.00 40.82 6
ATOM 2284 CB GLN C 109 22.000 58.258 186.195 1.00 40.78 6
ATOM 2285 CG GLN C 109 21.313 58.553 187.533 1.00 40.28 6
ATOM 2286 CD GLN C 109 22.289 58.666 188.701 1.00 40.51 6
ATOM 2287 OEl GLN C 109 21.885 58.969 189.822 1.00 41.49 8
ATOM 2288 NE2 GLN C 109 23.570 58.425 188.446 1.00 39.36 7
ATOM 2289 C GLN C 109 20.919 56.877 184.344 1.00 40.48 6
ATOM 2290 0 GLN C 109 20.026 56.110 184.692 1.00 40.71 8
ATOM 2291 N ASP C 110 21.795 56.565 183.397 1.00 40.06 7
ATOM 2292 CA ASP C 110 21.796 55.249 182.768 1.00 40.04 6
ATOM 2293 CB ASP C 110 22.547 55.289 181.444 1.00 40.23 6
ATOM 2294 CG ASP C 110 23.968 55.778 181.604 1.00 41.63 6
ATOM 2295 ODl ASP C 110 24.624 55.436 182.623 1.00 41.18 8
ATOM 2296 0D2 ASP C 110 24.427 56.512 180.699 1.00 44.25 8
ATOM 2297 C ASP C 110 22.457 54.264 183.708 1.00 39.48 6
ATOM 2298 0 ASP C 110 22.767 54.617 184.831 1.00 39.47 8
ATOM 2299 N LYS C 111 22.701 53.050 183.227 1.00 39.02 7
ATOM 2300 CA LYS C 111 23.208 51.961 184.056 1.00 38.58 6
ATOM 2301 CB LYS C 111 23.100 50.624 183.310 1.00 38.76 6
ATOM 2302 CG LYS C 111 24.258 50.323 182.325 1.00 38.60 6
ATOM 2303 CD LYS C 111 23.978 49.119 181.451 1.00 38.59 6
ATOM 2304 CE LYS C 111 25.226 48.269 181.331 1.00 40.61 6
ATOM 2305 NZ LYS C 111 25.109 47.136 180.357 1.00 41.56 7
ATOM 2306 C LYS C 111 24.640 52.172 184.538 1.00 38.35 6
ATOM 2307 O LYS C 111 25.102 51.443 185.401 1.00 38.35 8
ATOM 2308 N PHE C 112 25.348 53.149 183.975 1.00 38.15 7
ATOM 2309 CA PHE C 112 26.703 53.482 184.442 1.00 37.88 6
ATOM 2310 CB PHE C 112 27.620 53.815 183.260 1.00 37.96 6
ATOM 2311 CG PHE C 112 27.489 52.868 182.115 1.00 38.22 6
ATOM 2312 CDl PHE C 112 28.258 51.693 182.073 1.00 38.38 6
ATOM 2313 CEI PHE C 112 28.140 50.791 181.017 1.00 37.81 6
ATOM 2314 CZ PHE C 112 27.231 51.065 179.991 1.00 38.60 6
ATOM 2315 CE2 PHE C 112 26.448 52.238 180.028 1.00 38.16 6
ATOM 2316 CD2 PHE C 112 26.584 53.126 181.087 1.00 37.86 6
ATOM 2317 C PHE C 112 26.663 54.669 185.391 1.00 37.69 6
ATOM 2318 0 PHE C 112 27.697 55.160 185.820 1.00 37.50 8
ATOM 2319 N GLY C 113 25.457 55.138 185.687 1.00 37.67 7
ATOM 2320 CA GLY C 113 25.254 56.335 186.484 1.00 37.58 6
ATOM 2321 C GLY C 113 25.480 57.664 185.775 1.00 37.44 6
ATOM 2322 0 GLY C 113 25.557 58.708 186.437 1.00 37.78 8
ATOM 2323 N LYS C 114 25.589 57.643 184.448 1.00 37.00 7
ATOM 2324 CA LYS C 114 25.865 58.872 183.709 1.00 36.88 6
ATOM 2325 CB LYS C 114 26.584 58.582 182.405 1.00 36.44 6
ATOM 2326 CG LYS C 114 28.069 58.312 182.607 1.00 35.94 6
ATOM 2327 CD LYS C 114 28.843 58.493 181.312 1.00 34.40 6
ATOM 2328 CE LYS C 114 30.312 58.304 181.512 1.00 31.77 6
ATOM 2329 NZ LYS C 114 30.881 59.495 182.125 1.00 32.45 7
ATOM 2330 C LYS C 114 24.594 59.628 183.435 1.00 37.41 6
ATOM 2331 O LYS C 114 23.572 59.024 183.129 1.00 37.84 8
ATOM 2332 N THR C 115 24.649 60.946 183.559 1.00 38.00 7
ATOM 2333 CA THR C 115 23.508 61.796 183.233 1.00 38.74 6
ATOM 2334 CB THR C 115 23.352 62.921 184.254 1.00 38.86 6
ATOM 2335 OGl THR C 115 24.568 63.696 184.316 1.00 38.00 8 ATOM 2336 CG2 THR C 115 23.046 62.324 185.617 00 38.98
ATOM 2337 C THR C 115 23.806 62.443 181.907 00 39.20
ATOM 2338 0 THR C 115 24.978 62.489 181.501 00 39.29
ATOM 2339 N ALA C 116 22.780 62.973 181.239 00 39.35 7
ATOM 2340 CA ALA C 116 23.035 63.736 180.007 00 39.41 6
ATOM 2341 CB ALA C 116 21.764 64.388 179.475 00 39.66 6
ATOM 2342 C ALA C 116 24.153 64.776 180.192 00 39.29 6
ATOM 2343 0 ALA C 116 25.015 64.906 179.324 00 39.10 8
ATOM 2344 N PHE C 117 24.158 65.484 181.328 00 39.22 7
ATOM 2345 CA PHE C 117 25.224 66.456 181.584 00 38.99 6
ATOM 2346 CB PHE C 117 25.097 67.146 182.938 00 38.75 6
ATOM 2347 CG PHE C 117 26.283 68.037 183.270 00 38.22 6
ATOM 2348 CDl PHE C 117 26.400 69.308 182.712 00 38.91 6
ATOM 2349 CEI PHE C 117 27.491 70.132 183.002 1.00 37.81
ATOM 2350 CZ PHE C 117 28.461 69.687 183.846 1.00 37.25
ATOM 2351 CE2 PHE C 117 28.357 68.422 184.402 1.00 36.91
ATOM 2352 CD2 PHE C 117 27.280 67.606 184.117 1.00 36.76 6
ATOM 2353 C PHE C 117 26.605 65.836 181.478 1.00 38.96 6
ATOM 2354 0 PHE C 117 27.509 66.407 180.878 1.00 38.81 8
ATOM 2355 N ASP C 118 26.775 64.675 182.078 00 39.07 7
ATOM 2356 CA ASP C 118 28.040 64.010 181.963 00 39.54 6
ATOM 2357 CB ASP C 118 28.014 62.700 182.722 00 39.96 6
ATOM 2358 CG ASP C 118 27.830 62.904 184.201 00 41.79 6
ATOM 2359 ODl ASP C 118 28.352 63.903 184.749 00 43.06
ATOM 2360 0D2 ASP C 118 27.162 62.055 184.819 00 44.49
ATOM 2361 C ASP C 118 28.344 63.801 180.493 00 39.20 6
ATOM 2362 0 ASP C 118 29.375 64.262 179.996 1.00 39.16 8
ATOM 2363 N ILE C 119 27.416 63.149 179.795 1.00 38.64 7
ATOM 2364 CA ILE C 119 27.554 62.852 178.376 1.00 37.94
ATOM 2365 CB ILE C 119 26.228 62.367 177.807 1.00 37.56
ATOM 2366 CGl ILE C 119 26.032 60.908 178.186 1.00 37.32
ATOM 2367 CD ILE C 119 24.761 60.289 177.639 1.00 38.02
ATOM 2368 CG2 ILE C 119 26.216 62.493 176.324 1.00 37.65
ATOM 2369 C ILE C 119 28.085 64.050 177.593 1.00 37.90
ATOM 2370 0 ILE C 119 29.060 63.939 176.865 1.00 37.62
ATOM 2371 N SER C 120 27.462 65.203 177.783 00 38.22 7
ATOM 2372 CA SER C 120 27.850 66.417 177.067 00 38.94 6
ATOM 2373 CB SER C 120 26.886 67.539 177.388 00 39.23 6
ATOM 2374 OG SER C 120 26.699 67.588 178.792 00 41.18
ATOM 2375 C SER C 120 29.254 66.859 177.409 00 39.07
ATOM 2376 0 SER C 120 29.989 67.304 176.533 00 38.94
ATOM 2377 N ILE C 121 29.610 66.749 178.690 00 39.44 7
ATOM 2378 CA ILE C 121 30.978 66.975 179.130 00 39.57 6
ATOM 2379 CB ILE C 121 31.075 66.847 180.642 1.00 39.30 6
ATOM 2380 CGl ILE C 121 30.477 68.094 181.284 1.00 39.30 6
ATOM 2381 CD ILE C 121 31.284 69.375 181.037 1.00 40.20 6
ATOM 2382 CG2 ILE C 121 32.510 66.589 181.080 1.00 39.02 6
ATOM 2383 C ILE C 121 31.905 65.987 178.444 1.00 40.03 6
ATOM 2384 0 ILE C 121 32.908 66.398 177.863 1.00 39.94
ATOM 2385 N ASP C 122 31.532 64.702 178.487 1.00 40.70 7
ATOM 2386 CA ASP C 122 32.362 63.612 177.955 1.00 41.46 6
ATOM 2387 CB ASP C 122 31.785 62.216 178.227 1.00 41.47 6
ATOM 2388 CG ASP C 122 31.816 61.860 179.689 1.00 42.33
ATOM 2389 ODl ASP C 122 30.866 61.206 180.158 1.00 42.98
ATOM 2390 0D2 ASP C 122 32.774 62.265 180.380 1.00 43.75
ATOM 2391 C ASP C 122 32.645 63.766 176.492 1.00 41.62 ATOM 2392 O ASP C 122 33.742 63.464 176.064 00 42.05
ATOM 2393 N ASN C 123 31.694 64.222 175.698 00 41.91 7
ATOM 2394 CA ASN C 123 32.099 64.491 174.336 00 42.51 6
ATOM 2395 CB ASN C 123 31.347 63.674 173.255 00 42.56 6
ATOM 2396 CG ASN C 123 29.843 63.874 173.264 00 43.22 6
ATOM 2397 ODl ASN C 123 29.340 64.932 173.640 1.00 44.53 8
ATOM 2398 ND2 ASN C 123 29.111 62.853 172.813 ,00 42.66 7
ATOM 2399 C ASN C 123 32.275 65.959 174.052 .00 42.84 6
ATOM 2400 O ASN C 123 32.102 66.416 172.940 .00 42.80 8
ATOM 2401 N GLY C 124 32.651 66.679 175.099 .00 43.71 7
ATOM 2402 CA GLY C 124 33.152 68.041 174.979 .00 44.95 6
ATOM 2403 C GLY C 124 32.221 69.059 174.367 .00 45.71 6
ATOM 2404 O GLY C 124 32.664 70.095 173.931 1.00 45.65 8
ATOM 2405 N ASN C 125 30.928 68.768 174.344 1.00 46.94 7
ATOM 2406 CA ASN C 125 29.949 69.669 173.763 1.00 48.04 6
ATOM 2407 CB ASN C 125 28.818 68.855 173.107 1.00 47.86 6
ATOM 2408 CG ASN C 125 27.621 69.699 172.724 1.00 47.75 6
ATOM 2409 ODl ASN C 125 27.572 70.908 172.967 00 47.92 8
ATOM 2410 ND2 ASN C 125 26.634 69.057 172.130 1.00 47.94 7
ATOM 2411 C ASN C 125 29.452 70.600 174.855 00 49.07 6
ATOM 2412 O ASN C 125 28.439 70.322 175.504 00 49.36
ATOM 2413 N GLU C 126 30.168 71.699 175.082 1.00 50.61 7
ATOM 2414 CA GLU C 126 29.826 72.527 176.249 1.00 52.32 6
ATOM 2415 CB GLU C 126 31.051 73.125 176.981 1.00 52.16 6
ATOM 2416 CG GLU C 126 31.394 74.555 176.620 1.00 53.52 6
ATOM 2417 CD GLU C 126 31.956 74.696 175.214 1.00 54.93 6
ATOM 2418 OEl GLU C 126 33.174 74.947 175.105 1.00 56.03
ATOM 2419 0E2 GLU C 126 31.194 74.558 174.225 1.00 55.11
ATOM 2420 C GLU C 126 28.656 73.503 176.041 1.00 52.80
ATOM 2421 O GLU C 126 28.088 73.983 177.017 1.00 52.93
ATOM 2422 N ASP C 127 28.272 73.756 174.790 ,00 53.62 7
ATOM 2423 CA ASP C 127 27.014 74.453 174.526 .00 54.39 6
ATOM 2424 CB ASP C 127 26.756 74.617 173.019 1.00 54.71 6
ATOM 2425 CG ASP C 127 27.574 75.748 172.397 00 55.52
ATOM 2426 ODl ASP C 127 28.495 76.257 173.079 00 56.85
ATOM 2427 OD2 ASP C 127 27.299 76.123 171.228 00 56.04
ATOM 2428 C ASP C 127 25.885 73.680 175.198 00 54.69
ATOM 2429 0 ASP C 127 25.122 74.261 175.976 1.00 54.92
ATOM 2430 N LEU C 128 25.826 72.372 174.916 1. 00 54.90 7
ATOM 2431 CA LEU C 128 24.866 71.444 175.511 1.00 55.09 6
ATOM 2432 CB LEU C 128 25.130 70.034 175.003 1.00 55.04 6
ATOM 2433 CG LEU C 128 23.934 69.114 174.773 ,00 55.63 6
ATOM 2434 CDl LEU C 128 23.960 67.946 175.733 .00 56.08 6
ATOM 2435 CD2 LEU C 128 22.609 69.862 174.847 ,00 55.55 6
ATOM 2436 C LEU C 128 24.962 71.466 177.017 ,00 55.27 6
ATOM 2437 O LEU C 128 23.951 71.587 177.706 ,00 55.36 8
ATOM 2438 N ALA C 129 26.190 71.371 177.515 ,00 55.68 7
ATOM 2439 CA ALA C 129 26.460 71.434 178.948 ,00 56.41 6
ATOM 2440 CB ALA C 129 27.951 71.398 179.205 ,00 56.27 6
ATOM 2441 C ALA C 129 25.827 72.660 179.617 ,00 57.01 6
ATOM 2442 O ALA C 129 25.137 72.537 180.628 ,00 56.94 8
ATOM 2443 N GLU C 130 26.047 73.838 179.044 ,00 57.83 7
ATOM 2444 CA GLU C 130 25.456 75.049 179.591 ,00 58.73 6
ATOM 2445 CB GLU C 130 26.062 76.299 178.962 ,00 59.17 6
ATOM 2446 CG GLU C 130 27.411 76.674 179.549 ,00 61.40 6
ATOM 2447 CD GLU C 130 28.456 76.967 178.470 1.00 63.99 6 ATOM 2448 OEl GLU C 130 28.172 77.803 177.569 1.00 64.68 8
ATOM 2449 0E2 GLU C 130 29.556 76.352 178.530 1.00 64.72 8
ATOM 2450 C GLU C 130 23.941 75.083 179.478 1.00 58.52 6
ATOM 2451 0 GLU C 130 23.293 75.738 180.285 1.00 58.74 8
ATOM 2452 N ILE C 131 23.360 74.396 178.500 1.00 58.47 7
ATOM 2453 CA ILE C 131 21.909 74.401 178.437 1.00 58.57 6
ATOM 2454 CB ILE C 131 21.297 74.127 177.020 1.00 58.50 6
ATOM 2455 CGl ILE C 131 20.574 72.781 176.978 1.00 58.29 6
ATOM 2456 CD ILE C 131 19.296 72.819 176.189 1.00 58.30 6
ATOM 2457 CG2 ILE C 131 22.318 74.297 175.893 1.00 57.78 6
ATOM 2458 C ILE C 131 21.381 73.441 179.484 1.00 58.97 6
ATOM 2459 0 ILE C 131 20.226 73.514 179.878 1.00 59.06 8
ATOM 2460 N LEU C 132 22.240 72.554 179.955 1.00 59.62 7
ATOM 2461 CA LEU C 132 21.829 71.635 181.000 1.00 60.65 6
ATOM 2462 CB LEU C 132 22.459 70.253 180.777 1.00 60.38 6
ATOM 2463 CG LEU C 132 21.629 69.320 179.874 1.00 59.60 6
ATOM 2464 CDl LEU C 132 22.475 68.387 179.014 1.00 58.29 6
ATOM 2465 CD2 LEU C 132 20.582 68.533 180.681 1.00 58.81 6
ATOM 2466 C LEU C 132 22.082 72.199 182.405 1.00 61.76 6
ATOM 2467 0 LEU C 132 21.358 71.881 183.351 1.00 61.82 8
ATOM 2468 N GLN C 133 23.098 73.055 182.517 1.00 63.20 7
ATOM 2469 CA GLN C 133 23.368 73.828 183.734 1.00 64.65 6
ATOM 2470 CB GLN C 133 24.693 74.594 183.616 1.00 64.54 6
ATOM 2471 CG GLN C 133 25.919 73.732 183.599 1.00 64.14 6
ATOM 2472 CD GLN C 133 25.929 72.737 184.724 1.00 63.49 6
ATOM 2473 OEl GLN C 133 26.983 72.435 185.288 1.00 63.65 8
ATOM 2474 NE2 GLN C 133 24.752 72.214 185.065 1.00 62.66 7
ATOM 2475 C GLN C 133 22.278 74.850 183.999 1.00 66.11 6
ATOM 2476 0 GLN C 133 21.960 75.145 185.151 1.00 66.37 8
ATOM 2477 N LYS C 134 21.724 75.397 182.918 1.00 67.89 7
ATOM 2478 CA LYS C 134 20.731 76.469 182.977 1.00 69.50 6
ATOM 2479 CB LYS C 134 20.417 76.969 181.553 1.00 69.38 6
ATOM 2480 CG LYS C 134 20.526 78.476 181.327 1.00 69.23 6
ATOM 2481 CD LYS C 134 21.972 78.904 181.070 1.00 68.71 6
ATOM 2482 CE LYS C 134 22.099 79.745 179.806 1.00 68.48 6
ATOM 2483 NZ LYS C 134 21.155 80.901 179.749 1.00 68.07 7
ATOM 2484 C LYS C 134 19.446 76.001 183.677 1.00 70.74 6
ATOM 2485 0 LYS C 134 18.473 76.771 183.775 1.00 71.11 8
ATOM 2486 N LEU C 135 19.453 74.751 184.166 1.00 72.01 7
ATOM 2487 CA LEU C 135 18.269 74.145 184.794 1.00 73.28 6
ATOM 2488 CB LEU C 135 17.948 72.771 184.192 1.00 73.24 6
ATOM 2489 CG LEU C 135 17.071 72.844 182.931 1.00 74.03 6
ATOM 2490 CDl LEU C 135 17.255 71.594 182.093 1.00 74.85 6
ATOM 2491 CD2 LEU C 135 15.572 73.129 183.211 1.00 73.66 6
ATOM 2492 C LEU C 135 18.312 74.031 186.308 1.00 74.01 6
ATOM 2493 0 LEU C 135 19.358 73.744 186.890 1.00 74.20 8
ATOM 2494 N ASN C 136 17.153 74.312 186.913 1.00 74.92 7
ATOM 2495 CA ASN C 136 16.761 73.874 188.252 1.00 75.40 6
ATOM 2496 CB ASN C 136 15.236 73.729 188.280 1.00 75.53 6
ATOM 2497 CG ASN C 136 14.652 73.218 186.927 1.00 76.44 6
ATOM 2498 ODl ASN C 136 13.745 73.849 186.366 1.00 77.16 8
ATOM 2499 ND2 ASN C 136 15.175 72.081 186.411 1.00 76.82 7
ATOM 2500 C ASN C 136 17.384 72.536 188.634 1.00 75.59 6
ATOM 2501 0 ASN C 136 17.386 71.574 187.845 1.00 75.85 8
ATOM 2502 N SER D 12 57.072 76.469 149.223 1.00 71.66 7
ATOM 2503 CA SER D 12 57.218 75.497 150.357 1.00 72.01 6 ATOM 2504 CB SER D 12 58.177 76.071 151.421 1.00 72.13
ATOM 2505 OG SER D 12 59.438 76.408 150.868 1.00 72.16
ATOM 2506 C SER D 12 55.865 75.183 151.012 00 71.64
ATOM 2507 0 SER D 12 55.631 74.080 151.579 00 71.37
ATOM 2508 N ASP D 13 55.004 76.196 150.919 00 71.06 7
ATOM 2509 CA ASP D 13 53.670 76.236 151.512 1.00 70.55 6
ATOM 2510 CB ASP D 13 53.358 77.731 151.756 00 71.06 6
ATOM 2511 CG ASP D 13 52.015 77.989 152.458 00 72.21 6
ATOM 2512 ODl ASP D 13 52.045 78.420 153.649 00 73.06
ATOM 2513 0D2 ASP D 13 50.947 77.817 151.802 1.00 71.77
ATOM 2514 C ASP D 13 52.684 75.523 150.545 00 69.48
ATOM 2515 O ASP D 13 51.462 75.430 150.785 00 69.05
ATOM 2516 N LEU D 14 53.254 75.029 149.441 00 68.09 7
ATOM 2517 CA LEU D 14 52.637 74.008 148.609 00 66.41 6
ATOM 2518 CB LEU D 14 53.666 73.437 147.636 00 66.29 6
ATOM 2519 CG LEU D 14 53.966 74.228 146.369 00 65.59 6
ATOM 2520 CDl LEU D 14 55.222 73.727 145.680 00 65.76 6
ATOM 2521 CD2 LEU D 14 52.808 74.103 145.452 00 64.98 6
ATOM 2522 C LEU D 14 52.107 72.890 149.493 1.00 65.51 6
ATOM 2523 O LEU D 14 50.976 72.463 149.319 00 65.77 8
ATOM 2524 N GLY D 15 52.923 72.435 150.449 00 64.23 7
ATOM 2525 CA GLY D 15 52.501 71.453 151.460 00 62.41 6
ATOM 2526 C GLY D 15 51.178 71.709 152.174 1.00 61.18 6
ATOM 2527 0 GLY D 15 50.329 70.828 152.243 00 60.79
ATOM 2528 N LYS D 16 50.994 72.918 152.698 00 60.20 7
ATOM 2529 CA LYS D 16 49.745 73.272 153.382 00 58.81 6
ATOM 2530 CB LYS D 16 49.862 74.629 154.071 00 58.79 6
ATOM 2531 CG LYS D 16 48.662 75.033 154.922 1.00 58.52 6
ATOM 2532 CD LYS D 16 48.936 76.320 155.708 00 58.76
ATOM 2533 CE LYS D 16 47.724 76.754 156.535 00 58.71
ATOM 2534 NZ LYS D 16 48.103 11.121 157.589 00 57.71 7
ATOM 2535 C LYS D 16 48.557 73.242 152.438 00 58.00 6
ATOM 2536 0 LYS D 16 47.454 72.947 152.846 1.00 57.61 8
ATOM 2537 N LYS D 17 48.796 73.536 151.172 1.00 57.54 7
ATOM 2538 CA LYS D 17 47.756 73.458 150.144 00 57.33 6
ATOM 2539 CB LYS D 17 48.242 74.157 148.854 00 57.47 6
ATOM 2540 CG LYS D 17 48.360 75.682 148.918 00 57.59 6
ATOM 2541 CD LYS D 17 47.077 76.337 148.462 00 58.43 6
ATOM 2542 CE LYS D 17 46.732 77.561 149.310 00 60.29 6
ATOM 2543 NZ LYS D 17 46.653 78.874 148.554 00 61.03 7
ATOM 2544 C LYS D 17 47.346 71.995 149.843 00 56.68 6
ATOM 2545 O LYS D 17 46.162 71.648 149.756 00 56.26 8
ATOM 2546 N LEU D 18 48.348 71.147 149.677 00 56.01 7
ATOM 2547 CA LEU D 18 48.114 69.750 149.427 00 55.59 6
ATOM 2548 CB LEU D 18 49.432 69.015 149.255 00 55.04 6
ATOM 2549 CG LEU D 18 49.290 67.529 148.944 00 54.58 6
ATOM 2550 CDl LEU D 18 48.236 67.250 147.865 00 54.03 6
ATOM 2551 CD2 LEU D 18 50.633 66.931 148.538 00 55.07 6
ATOM 2552 C LEU D 18 47.297 69.128 150.550 00 55.76 6
ATOM 2553 0 LEU D 18 46.322 68.403 150.297 00 55.89 8
ATOM 2554 N LEU D 19 47.683 69.423 151.787 00 55.74 7
ATOM 2555 CA LEU D 19 46.954 68.918 152.937 00 55.74 6
ATOM 2556 CB LEU D 19 47.542 69.451 154.244 00 55.23 6
ATOM 2557 CG LEU D 19 48.845 68.723 154.600 .00 54.59 6
ATOM 2558 CDl LEU D 19 49.729 69.448 155.607 .00 53.41 6
ATOM 2559 CD2 LEU D 19 48.542 67.307 155.067 1.00 54.86 6 ATOM 2560 C LEU D 19 45.485 69.257 152.784 1.00 56.26
ATOM 2561 O LEU D 19 44.638 68.355 152.778 1.00 55.97
ATOM 2562 N GLU D 20 45.202 70.547 152.588 1.00 56.94 7
ATOM 2563 CA GLU D 20 43.822 71.035 152.464 .00 58.02 6
ATOM 2564 CB GLU D 20 43.769 72.578 152.421 .00 57.73 6
ATOM 2565 CG GLU D 20 44.234 73.253 153.754 .00 60.07 6
ATOM 2566 CD GLU D 20 44.638 74.769 153.653 1.00 61.13 6
ATOM 2567 OEl GLU D 20 45.124 75.269 152.589 ,00 64.85
ATOM 2568 0E2 GLU D 20 44.488 75.469 154.684 .00 64.45
ATOM 2569 C GLU D 20 43.065 70.370 151.300 1.00 57.32
ATOM 2570 0 GLU D 20 41.883 70.032 151.434 00 57.14
ATOM 2571 N ALA D 21 43.762 70.136 150.189 00 56.99 7
ATOM 2572 CA ALA D 21 43.118 69.578 149.017 1.00 56.48 6
ATOM 2573 CB ALA D 21 43.973 69.769 147.815 .00 56.52 6
ATOM 2574 C ALA D 21 42.822 68.118 149.263 .00 56.48 6
ATOM 2575 O ALA D 21 41.782 67.619 148.845 1.00 56.37 8
ATOM 2576 N ALA D 22 43.723 67.439 149.971 .00 56.56 7
ATOM 2577 CA ALA D 22 43.479 66.051 150.345 .00 56.55 6
ATOM 2578 CB ALA D 22 44.715 65.424 150.925 ,00 56.59 6
ATOM 2579 C ALA D 22 42.276 65.909 151.288 .00 56.59 6
ATOM 2580 0 ALA D 22 41.430 65.070 151.049 .00 56.50 8
ATOM 2581 N ARG D 23 42.173 66.740 152.325 1.00 56.73 7
ATOM 2582 CA ARG D 23 40.974 66.729 153.182 1.00 57.41 6
ATOM 2583 CB ARG D 23 41.049 67.803 154.286 1.00 57.14 6
ATOM 2584 CG ARG D 23 39.795 67.850 155.195 1.00 57.96 6
ATOM 2585 CD ARG D 23 39.749 69.085 156.109 1.00 59.45 6
ATOM 2586 NE ARG D 23 40.494 68.922 157.373 1.00 64.37 7
ATOM 2587 CZ ARG D 23 41.731 69.385 157.623 1.00 65.22 6
ATOM 2588 NHl ARG D 23 42.439 70.068 156.707 1.00 64.16 7
ATOM 2589 NH2 ARG D 23 42.272 69.151 158.812 1.00 64.98 7
ATOM 2590 C ARG D 23 39.690 66.928 152.364 1.00 57.10 6
ATOM 2591 0 ARG D 23 38.664 66.275 152.587 1.00 56.90 8
ATOM 2592 N ALA D 24 39.770 67.836 151.408 .00 57.16 7
ATOM 2593 CA ALA D 24 38.597 68.296 150.720 .00 57.23 6
ATOM 2594 CB ALA D 24 38.868 69.626 150.087 1.00 57.24 6
ATOM 2595 C ALA D 24 38.113 67.306 149.687 .00 57.52 6
ATOM 2596 O ALA D 24 36.926 67.254 149.399 .00 57.76 8
ATOM 2597 N GLY D 25 39.019 66.515 149.131 1.00 57.87 7
ATOM 2598 CA GLY D 25 38.652 65.638 148.028 00 58.24 6
ATOM 2599 C GLY D 25 38.828 66.258 146.647 00 58.65 6
ATOM 2600 O GLY D 25 38.422 65.671 145.653 1.00 58.41 8
ATOM 2601 N GLN D 26 39.449 67.431 146.576 .00 59.14 7
ATOM 2602 CA GLN D 26 39.786 68.038 145.304 .00 60.00 6
ATOM 2603 CB GLN D 26 40.098 69.505 145.513 .00 60.16 6
ATOM 2604 CG GLN D 26 39.250 70.142 146.605 1.00 61.63 6
ATOM 2605 CD GLN D 26 37.923 70.738 146.128 00 64.20 6
ATOM 2606 OEl GLN D 26 37.344 70.323 145.114 00 65.91 8
ATOM 2607 NE2 GLN D 26 37.427 71.719 146.879 1.00 64.88 7
ATOM 2608 C GLN D 26 40.932 67.292 144.596 .00 60.60 6
ATOM 2609 0 GLN D 26 42.117 67.608 144.765 .00 60.40
ATOM 2610 N ASP D 27 40.549 66.291 143.799 .00 61.48 7
ATOM 2611 CA ASP D 27 41.500 65.421 143.102 .00 62.13 6
ATOM 2612 CB ASP D 27 40.830 64.190 142.480 .00 62.51 6
ATOM 2613 CG ASP D 27 39.481 63.858 143.110 .00 64.47 6
ATOM 2614 ODl ASP D 27 39.342 62.777 143.749 1.00 66.51
ATOM 2615 0D2 ASP D 27 38.549 64.682 142.952 1.00 66.12 ATOM 2616 C ASP D 27 42.302 66.159 142.045 1.00 62.16
ATOM 2617 0 ASP D 27 43.477 65.864 141.879 1.00 62.57
ATOM 2618 N ASP D 28 41.694 67.103 141.335 1.00 61.96 7
ATOM 2619 CA ASP D 28 42.454 67.896 140.390 1.00 62.30 6
ATOM 2620 CB ASP D 28 41.548 68.786 139.591 1.00 62.90 6
ATOM 2621 CG ASP D 28 40.866 68.041 138.496 ,00 65.47
ATOM 2622 ODl ASP D 28 41.244 66.857 138.274 .00 67.62
ATOM 2623 0D2 ASP D 28 39.951 68.633 137.867 .00 66.86
ATOM 2624 C ASP D 28 43.452 68.759 141.077 .00 61.98 6
ATOM 2625 0 ASP D 28 44.583 68.863 140.629 .00 62.11 8
ATOM 2626 N GLU D 29 43.011 69.392 142.159 ,00 61.73 7
ATOM 2627 CA GLU D 29 43.860 70.228 142.999 00 61.32 6
ATOM 2628 CB GLU D 29 43.061 70.738 144.204 00 61.59 6
ATOM 2629 CG GLU D 29 42.714 72.205 144.181 00 63.74 6
ATOM 2630 CD GLU D 29 43.975 73.058 144.244 00 68.32 6
ATOM 2631 OEl GLU D 29 44.634 73.193 143.176 00 69.59
ATOM 2632 OE2 GLU D 29 44.318 73.579 145.350 00 69.36
ATOM 2633 C GLU D 29 45.073 69.437 143.467 00 60.51
ATOM 2634 0 GLU D 29 46.201 69.941 143.456 00 60.69
ATOM 2635 N VAL D 30 44.832 68.188 143.858 00 59.25 7
ATOM 2636 CA VAL D 30 45.892 67.313 144.306 00 58.04 6
ATOM 2637 CB VAL D 30 45.315 65.986 144.832 00 57.79 6
ATOM 2638 CGl VAL D 30 46.428 65.005 145.224 00 57.27 6
ATOM 2639 CG2 VAL D 30 44.446 66.260 146.021 00 57.41 6
ATOM 2640 C VAL D 30 46.896 67.106 143.176 .00 57.60 6
ATOM 2641 0 VAL D 30 48.079 67.355 143.333 1 00 57.42 8
ATOM 2642 N ARG D 31 46.386 66.695 142.031 1 00 57.24 7
ATOM 2643 CA ARG D 31 47.159 66.392 140.843 1 00 57.14 6
ATOM 2644 CB ARG D 31 46.153 66.085 139.757 1 00 57.14 6
ATOM 2645 CG ARG D 31 46.359 64.798 139.064 1 00 58.78 6
ATOM 2646 CD ARG D 31 45.099 64.491 138.286 1 00 61.86 6
ATOM 2647 NE ARG D 31 44.077 63.782 139.076 1 00 63.51 7
ATOM 2648 CZ ARG D 31 42.771 63.758 138.777 1 00 63.63 6
ATOM 2649 NHl ARG D 31 42.294 64.425 137.725 1 00 62.62 7
ATOM 2650 NH2 ARG D 31 41.927 63.072 139.540 1 00 64.17 7
ATOM 2651 C ARG D 31 47.989 67.576 140.385 1.00 56.73 6
ATOM 2652 0 ARG D 31 49.127 67.430 139.911 1.00 56.39 8
ATOM 2653 N ILE D 32 47.373 68.749 140.512 ,00 56.50 7
ATOM 2654 CA ILE D 32 47.971 70.008 140.126 ,00 56.15 6
ATOM 2655 CB ILE D 32 46.921 71.142 140.059 ,00 56.07 6
ATOM 2656 CGl ILE D 32 45.991 70.962 138.858 ,00 55.42 6
ATOM 2657 CD ILE D 32 44.830 71.940 138.839 ,00 55.57 6
ATOM 2658 CG2 ILE D 32 47.590 72.487 139.926 ,00 56.57 6
ATOM 2659 C ILE D 32 49.106 70.337 141.083 ,00 56.23
ATOM 2660 0 ILE D 32 50.166 70.757 140.646 .00 56.54
ATOM 2661 N LEU D 33 48.898 70.118 142.379 1.00 56.26
ATOM 2662 CA LEU D 33 49.977 70.265 143.370 1.00 56.10
ATOM 2663 CB LEU D 33 49.409 70.214 144.767 1.00 55.63
ATOM 2664 CG LEU D 33 48.540 71.432 144.996 1.00 55.06
ATOM 2665 CDl LEU D 33 47.580 71.158 146.123 1.00 56.17
ATOM 2666 CD2 LEU D 33 49.414 72.611 145.297 ,00 53.85
ATOM 2667 C LEU D 33 51.102 69.244 143.206 ,00 56.15
ATOM 2668 0 LEU D 33 52.262 69.548 143.385 .00 56.01
ATOM 2669 N MET D 34 50.748 68.031 142.841 .00 56.56 7
ATOM 2670 CA MET D 34 51.736 67.056 142.472 1.00 57.10 6
ATOM 2671 CB MET D 34 51.065 65.756 142.042 1.00 57.30 6 ATOM 2672 CG MET D 34 50.190 65.176 143.142 00 58.41 6
ATOM 2673 SD MET D 34 51.150 64.520 144.521 ,00 62.08 16
ATOM 2674 CE MET D 34 51.913 65.938 145.301 ,00 60.18 6
ATOM 2675 C MET D 34 52.602 67.611 141.369 ,00 57.05 6
ATOM 2676 0 MET D 34 53.819 67.665 141.512 1.00 57.43 8
ATOM 2677 N ALA D 35 51.969 68.044 140.284 ,00 56.82 7
ATOM 2678 CA ALA D 35 52.677 68.571 139.123 ,00 56.49 6
ATOM 2679 CB ALA D 35 51.696 69.124 138.129 ,00 56.34 6
ATOM 2680 C ALA D 35 53.673 69.646 139.523 00 56.33 6
ATOM 2681 0 ALA D 35 54.782 69.673 139.000 ,00 56.69 8
ATOM 2682 N ASN D 36 53.268 70.510 140.458 ,00 55.73 7
ATOM 2683 CA ASN D 36 54.103 71.565 141.007 ,00 54.98 6
ATOM 2684 CB ASN D 36 53.235 72.595 141.649 00 54.62 6
ATOM 2685 CG ASN D 36 52.666 73.508 140.666 ,00 55.34 6
ATOM 2686 ODl ASN D 36 53.399 74.244 140.014 ,00 57.80 8
ATOM 2687 ND2 ASN D 36 51.347 73.483 140.519 ,00 54.88 7
ATOM 2688 C ASN D 36 55.042 71.098 142.067 ,00 54.87 6
ATOM 2689 0 ASN D 36 55.607 71.921 142.786 00 55.18 8
ATOM 2690 N GLY D 37 55.171 69.782 142.192 ,00 54.57 7
ATOM 2691 CA GLY D 37 56.092 69.159 143.128 ,00 54.08 6
ATOM 2692 C GLY D 37 55.829 69.345 144.613 ,00 53.79 6
ATOM 2693 0 GLY D 37 56.765 69.369 145.391 1.00 53.85
ATOM 2694 N ALA D 38 54.568 69.469 145.019 00 53.57 7
ATOM 2695 CA ALA D 38 54.216 69.541 146.440 00 53.06 6
ATOM 2696 CB ALA D 38 52.723 69.626 146.618 00 52.86
ATOM 2697 C ALA D 38 54.738 68.300 147.118 1.00 52.85
ATOM 2698 0 ALA D 38 54.835 67.247 146.473 00 53.01
ATOM 2699 N ASP D 39 55.081 68.425 148.401 00 52.44 7
ATOM 2700 CA ASP D 39 55.623 67.309 149.166 00 52.26 6
ATOM 2701 CB ASP D 39 56.372 67.809 150.393 00 52.02
ATOM 2702 CG ASP D 39 56.714 66.686 151.388 00 53.04
ATOM 2703 ODl ASP D 39 56.710 65.472 151.040 00 52.47
ATOM 2704 0D2 ASP D 39 57.001 67.037 152.548 00 54.96
ATOM 2705 C ASP D 39 54.522 66.343 149.591 00 52.11
ATOM 2706 0 ASP D 39 53.676 66.690 150.427 00 52.33
ATOM 2707 N VAL D 40 54.568 65.123 149.046 00 51.38 7
ATOM 2708 CA VAL D 40 53.517 64.135 149.254 00 50.70 6
ATOM 2709 CB VAL D 40 53.732 62.874 148.342 00 50.57 6
ATOM 2710 CGl VAL D 40 54.702 61.950 148.948 00 50.64 6
ATOM 2711 CG2 VAL D 40 52.451 62.121 148.097 00 50.05 6
ATOM 2712 C VAL D 40 53.422 63.785 150.741 00 50.44 6
ATOM 2713 0 VAL D 40 52.436 63.206 151.196 00 50.33 8
ATOM 2714 N ASN D 41 54.433 64.173 151.506 00 50.12 7
ATOM 2715 CA ASN D 41 54.445 63.833 152.919 00 50.06 6
ATOM 2716 CB ASN D 41 55.639 62.941 153.247 00 49.98 6
ATOM 2717 CG ASN D 41 55.477 61.547 152.697 00 49.62 6
ATOM 2718 ODl ASN D 41 54.365 61.091 152.439 00 50.47 8
ATOM 2719 ND2 ASN D 41 56.584 60.865 152.502 1.00 49.83 7
ATOM 2720 C ASN D 41 54.339 64.973 153.900 00 50.08 6
ATOM 2721 0 ASN D 41 54.575 64.801 155.088 00 50.24
ATOM 2722 N ALA D 42 53.955 66.136 153.412 00 50.00 7
ATOM 2723 CA ALA D 42 53.717 67.262 154.284 00 50.36 6
ATOM 2724 CB ALA D 42 52.917 68.259 153.525 00 50.44 6
ATOM 2725 C ALA D 42 52.970 66.859 155.581 00 50.66 6
ATOM 2726 0 ALA D 42 51.997 66.086 155.496 00 51.10
ATOM 2727 N ASN D 43 53.412 67.351 156.758 1.00 50.17 ATOM 2728 CA ASN D 43 52.612 67.199 158.000 1.00 49.75 6
ATOM 2729 CB ASN D 43 53.467 66.907 159.219 1.00 50.10 6
ATOM 2730 CG ASN D 43 54.285 65.667 159.078 1.00 51.24 6
ATOM 2731 ODl ASN D 43 54.319 65.069 158.000 1.00 53.03 8
ATOM 2732 ND2 ASN D 43 54.980 65.269 160.166 1.00 51.07 7
ATOM 2733 C ASN D 43 51.822 68.432 158.347 1.00 49.34 6
ATOM 2734 0 ASN D 43 52.269 69.538 158.073 1.00 49.80 8
ATOM 2735 N ASP D 44 50.665 68.249 158.975 1.00 48.59 7
ATOM 2736 CA ASP D 44 49.991 69.351 159.642 1.00 48.29 6
ATOM 2737 CB ASP D 44 48.491 69.140 159.620 1.00 48.73 6
ATOM 2738 CG ASP D 44 48.062 67.918 160.408 1.00 51.34 6
ATOM 2739 ODl ASP D 44 48.877 67.308 161.140 1.00 53.22 8
ATOM 2740 0D2 ASP D 44 46.876 67.563 160.298 1.00 54.79 8
ATOM 2741 C ASP D 44 50.535 69.382 161.065 1.00 47.49 6
ATOM 2742 0 ASP D 44 51.431 68.616 161.372 1.00 47.43 8
ATOM 2743 N ARG D 45 50.023 70.233 161.952 1.00 46.84 7
ATOM 2744 CA ARG D 45 50.706 70.332 163.251 1.00 46.04 6
ATOM 2745 CB ARG D 45 50.417 71.600 164.059 1.00 45.97 6
ATOM 2746 CG ARG D 45 49.075 71.701 164.644 1.00 45.40 6
ATOM 2747 CD ARG D 45 49.037 72.816 165.619 1.00 43.85 6
ATOM 2748 NE ARG D 45 48.817 72.309 166.953 1.00 43.16 7
ATOM 2749 CZ ARG D 45 47.688 71.747 167.369 1.00 43.41 6
ATOM 2750 NHl ARG D 45 46.667 71.579 166.555 1.00 44.48 7
ATOM 2751 NH2 ARG D 45 47.579 71.329 168.613 1.00 44.79 7
ATOM 2752 C ARG D 45 50.540 69.121 164.093 1.00 45.37 6
ATOM 2753 0 ARG D 45 51.354 68.888 164.962 1.00 45.16 8
ATOM 2754 N LYS D 46 49.511 68.332 163.832 1.00 44.85 7
ATOM 2755 CA LYS D 46 49.412 67.077 164.535 1.00 44.82 6
ATOM 2756 CB LYS D 46 48.093 66.936 165.275 1.00 44.58 6
ATOM 2757 CG LYS D 46 47.004 67.704 164.632 1.00 47.35 6
ATOM 2758 CD LYS D 46 45.649 67.019 164.834 1.00 52.56 6
ATOM 2759 CE LYS D 46 44.959 67.475 166.138 1.00 53.29 6
ATOM 2760 NZ LYS D 46 45.855 67.391 167.329 1.00 53.75 7
ATOM 2761 C LYS D 46 49.759 65.878 163.643 1.00 44.52 6
ATOM 2762 0 LYS D 46 49.085 64.841 163.681 1.00 44.87 8
ATOM 2763 N GLY D 47 50.838 66.033 162.867 1.00 44.00 7
ATOM 2764 CA GLY D 47 51.527 64.936 162.185 1.00 43.24 6
ATOM 2765 C GLY D 47 50.797 64.191 161.082 1.00 43.13 6
ATOM 2766 0 GLY D 47 51.317 63.211 160.536 1.00 43.35 8
ATOM 2767 N ASN D 48 49.592 64.630 160.750 1.00 42.76 7
ATOM 2768 CA ASN D 48 48.877 64.046 159.643 1.00 42.83 6
ATOM 2769 CB ASN D 48 47.467 64.600 159.611 1.00 43.56 6
ATOM 2770 CG ASN D 48 46.596 64.019 160.720 1.00 47.03 6
ATOM 2771 ODl ASN D 48 46.662 62.790 161.032 1.00 50.61 8
ATOM 2772 ND2 ASN D 48 45.782 64.886 161.344 1.00 48.47 7
ATOM 2773 C ASN D 48 49.568 64.303 158.325 1.00 42.22 6
ATOM 2774 0 ASN D 48 50.169 65.342 158.144 1.00 42.65 8
ATOM 2775 N THR D 49 49.513 63.347 157.416 1.00 41.68 7
ATOM 2776 CA THR D 49 49.959 63.581 156.057 1.00 41.50 6
ATOM 2777 CB THR D 49 50.777 62.403 155.517 1.00 41.96 6
ATOM 2778 OGl THR D 49 49.956 61.221 155.443 1.00 41.45 8
ATOM 2779 CG2 THR D 49 52.039 62.166 156.362 1.00 42.52 6
ATOM 2780 C THR D 49 48.743 63.717 155.162 1.00 41.13 6
ATOM 2781 0 THR D 49 47.621 63.473 155.591 1.00 41.16 8
ATOM 2782 N PRO D 50 48.956 64.100 153.905 1.00 40.74 7
ATOM 2783 CA PRO D 50 47.848 64.047 152.975 1.00 40.47 6 ATOM 2784 CB PRO D 50 48.507 64.273 151.632 00 40.26
ATOM 2785 CG PRO D 50 49.719 65.051 151.962 00 40.72
ATOM 2786 CD PRO D 50 50.190 64.592 153.281 00 40.54
ATOM 2787 C PRO D 50 47.216 62.675 152.978 00 40.30
ATOM 2788 0 PRO D 50 45.981 62.588 152.989 00 40.43
ATOM 2789 N LEU D 51 48.031 61.613 152.991 00 39.72 7
ATOM 2790 CA LEU D 51 47.459 60.272 152.922 00 39.50 6
ATOM 2791 CB LEU D 51 48.498 59.178 152.655 00 39.61 6
ATOM 2792 CG LEU D 51 48.005 57.711 152.693 00 39.41 6
ATOM 2793 CDl LEU D 51 47.220 57.340 151.464 00 38.04 6
ATOM 2794 CD2 LEU D 51 49.126 56.692 152.932 1.00 39.18 6
ATOM 2795 C LEU D 51 46.615 59.971 154.154 00 39.58 6
ATOM 2796 O LEU D 51 45.551 59.383 154.022 00 39.70
ATOM 2797 N HIS D 52 47.063 60.389 155.334 00 39.49
ATOM 2798 CA HIS D 52 46.198 60.367 156.501 00 39.72
ATOM 2799 CB HIS D 52 46.792 61.139 157.664 1.00 39.89 6
ATOM 2800 CG HIS D 52 47.821 60.384 158.438 00 42.02 6
ATOM 2801 NDl HIS D 52 49.143 60.111 158.500 00 43.64 7
ATOM 2802 CEI HIS D 52 49.815 59.933 159.261 1.00 44.05 6
ATOM 2803 NE2 HIS D 52 48.978 59.005 159.694 00 43.73 7
ATOM 2804 CD2 HIS D 52 47.724 59.267 159.197 00 43.38
ATOM 2805 C HIS D 52 44.871 61.017 156.172 1.00 39.71
ATOM 2806 0 HIS D 52 43.827 60.372 156.258 00 39.97
ATOM 2807 N LEU D 53 44.886 62.292 155.795 00 39.54 7
ATOM 2808 CA LEU D 53 43.622 63.000 155.682 00 39.69 6
ATOM 2809 CB LEU D 53 43.801 64.482 155.395 00 39.80 6
ATOM 2810 CG LEU D 53 44.704 65.268 156.330 00 40.31 6
ATOM 2811 CDl LEU D 53 44.856 66.684 155.821 00 41.23 6
ATOM 2812 CD2 LEU D 53 44.162 65.251 157.754 00 41.39 6
ATOM 2813 C LEU D 53 42.760 62.368 154.626 00 39.96 6
ATOM 2814 O LEU D 53 41.546 62.239 154.817 00 40.69 8
ATOM 2815 N ALA D 54 43.370 61.949 153.526 00 39.83 7
ATOM 2816 CA ALA D 54 42.590 61.323 152.474 00 40.18 6
ATOM 2817 CB ALA D 54 43.438 61.085 151.280 00 40.73 6
ATOM 2818 C ALA D 54 41.937 60.022 152.963 00 40.43 6
ATOM 2819 O ALA D 54 40.779 59.734 152.637 00 40.45 8
ATOM 2820 N ALA D 55 42.675 59.247 153.755 00 40.53 7
ATOM 2821 CA ALA D 55 42.098 58.085 154.427 00 40.76 6
ATOM 2822 CB ALA D 55 43.144 57.367 155.255 00 40.58 6
ATOM 2823 C ALA D 55 40.962 58.548 155.312 1.00 41.05 6
ATOM 2824 0 ALA D 55 39.850 58.050 155.209 00 41.23
ATOM 2825 N ASP D 56 41.256 59.528 156.161 00 41.19 7
ATOM 2826 CA ASP D 56 40.314 60.038 157.130 00 41.51 6
ATOM 2827 CB ASP D 56 40.938 61.226 157.874 00 41.73 6
ATOM 2828 CG ASP D 56 40.240 61.512 159.199 00 43.95 6
ATOM 2829 ODl ASP D 56 39.016 61.797 159.198 00 46.40
ATOM 2830 0D2 ASP D 56 40.905 61.454 160.260 00 46.26
ATOM 2831 C ASP D 56 38.942 60.394 156.534 00 41.43
ATOM 2832 0 ASP D 56 37.928 60.204 157.200 00 41.20
ATOM 2833 N TYR D 57 38.917 60.882 155.286 00 41.74 7
ATOM 2834 CA TYR D 57 37.680 61.416 154.640 00 42.19 6
ATOM 2835 CB TYR D 57 37.930 62.869 154.209 00 41.96 6
ATOM 2836 CG TYR D 57 38.023 63.787 155.379 00 41.76 6
ATOM 2837 CDl TYR D 57 39.115 63.738 156.230 1.00 41.22 6
ATOM 2838 CEI TYR D 57 39.200 64.562 157.336 1.00 41.61 6
ATOM 2839 CZ TYR D 57 38.186 65.460 157.601 1.00 42.46 6 ATOM 2840 OH TYR D 57 38.294 66.277 158.703 00 43.34
ATOM 2841 CE2 TYR D 57 37.072 65.531 156.773 00 42.25
ATOM 2842 CD2 TYR D 57 36.998 64.685 155.668 00 42.19
ATOM 2843 C TYR D 57 37.206 60.585 153.433 00 42.47
ATOM 2844 0 TYR D 57 36.822 61.132 152.411 00 42.33
ATOM 2845 N ASP D 58 37.185 59.267 153.587 00 43.05 7
ATOM 2846 CA ASP D 58 37.600 58.402 152.491 00 43.89 6
ATOM 2847 CB ASP D 58 37.034 56.984 152.575 00 43.92 6
ATOM 2848 CG ASP D 58 35.583 56.954 152.365 00 44.00 6
ATOM 2849 ODl ASP D 58 35.018 58.054 152.376 00 44.16
ATOM 2850 0D2 ASP D 58 35.015 55.863 152.174 1.00 44.65
ATOM 2851 C ASP D 58 37.481 59.024 151.103 00 44.35
ATOM 2852 0 ASP D 58 36.404 59.294 150.583 00 43.98
ATOM 2853 N HIS D 59 38.656 59.241 150.541 00 45.45 7
ATOM 2854 CA HIS D 59 38.826 59.765 149.223 00 46.45 6
ATOM 2855 CB HIS D 59 39.527 61.111 149.332 00 46.36 6
ATOM 2856 CG HIS D 59 38.633 62.201 149.837 00 47.07 6
ATOM 2857 NDl HIS D 59 37.352 62.387 149.369 00 47.38 7
ATOM 2858 CEI HIS D 59 36.801 63.417 149.986 00 47.75 6
ATOM 2859 NE2 HIS D 59 37.680 63.913 150.835 1.00 47.98 7
ATOM 2860 CD2 HIS D 59 38.835 63.170 150.761 1.00 48.40 6
ATOM 2861 C HIS D 59 39.661 58.742 148.492 1.00 46.98 6
ATOM 2862 0 HIS D 59 40.877 58.879 148.377 1.00 47.24 8
ATOM 2863 N LEU D 60 38.989 57.703 148.019 1.00 47.63 7
ATOM 2864 CA LEU D 60 39.667 56.527 147.508 1. 00 48.47 6
ATOM 2865 CB LEU D 60 38.676 55.559 146.854 1.00 48.69 6
ATOM 2866 CG LEU D 60 39.214 54.183 146.452 1.00 47.75 6
ATOM 2867 CDl LEU D 60 39.881 53.552 147.639 1.00 47.41 6
ATOM 2868 CD2 LEU D 60 38.104 53.270 145.940 1.00 48.12 6
ATOM 2869 C LEU D 60 40.709 56.889 146.497 1.00 49.37 6
ATOM 2870 0 LEU D 60 41.850 56.479 146.629 1.00 49.75 8
ATOM 2871 N GLU D 61 40.306 57.645 145.479 1.00 50.35 7
ATOM 2872 CA GLU D 61 41.176 57.927 144.327 1.00 51.65 6
ATOM 2873 CB GLU D 61 40.435 58.503 143.096 1.00 52.16 6
ATOM 2874 CG GLU D 61 39.328 59.530 143.409 1.00 57.83 6
ATOM 2875 CD GLU D 61 38.344 59.058 144.527 1.00 64.50 6
ATOM 2876 OEl GLU D 61 38.537 59.433 145.741 1.00 65.38
ATOM 2877 0E2 GLU D 61 37.403 58.284 144.178 1.00 66.25
ATOM 2878 C GLU D 61 42.343 58.770 144.764 1.00 51.09
ATOM 2879 0 GLU D 61 43.487 58.403 144.476 1.00 51.37
ATOM 2880 N ILE D 62 42.076 59.847 145.509 1.00 50.59 7
ATOM 2881 CA ILE D 62 43.175 60.640 146.082 1.00 50.05 6
ATOM 2882 CB ILE D 62 42.717 61.735 147.046 1.00 49.93 6
ATOM 2883 CGl ILE D 62 41.946 62.832 146.297 1.00 49.95 6
ATOM 2884 CD ILE D 62 41.808 64.172 147.092 .00 49.66 6
ATOM 2885 CG2 ILE D 62 43.924 62.312 147.791 .00 48.28 6
ATOM 2886 C ILE D 62 44.175 59.747 146.815 1.00 50.09 6
ATOM 2887 0 ILE D 62 45.391 59.902 146.649 1.00 50.31 8
ATOM 2888 N VAL D 63 43.668 58.800 147.601 1, 00 49.72 7
ATOM 2889 CA VAL D 63 44.549 57.879 148.292 1.00 49.62 6
ATOM 2890 CB VAL D 63 43.788 56.814 149.086 1.00 49.10 6
ATOM 2891 CGl VAL D 63 44.723 55.739 149.554 1.00 48.31 6
ATOM 2892 CG2 VAL D 63 43.131 57.425 150.267 1.00 48.71 6
ATOM 2893 C VAL D 63 45.472 57.232 147.280 1.00 50.33 6
ATOM 2894 0 VAL D 63 46.689 57.192 147.472 1.00 50.30
ATOM 2895 N GLU D 64 44.901 56.765 146.178 1.00 51.16 ATOM 2896 CA GLU D 64 45.698 56.058 145.197 1.00 52.39 6
ATOM 2897 CB GLU D 64 44.801 55.356 144.206 1.00 52.50 6
ATOM 2898 CG GLU D 64 45.290 53.947 143.915 1.00 55.95 6
ATOM 2899 CD GLU D 64 44.135 52.950 143.750 1.00 60.39 6
ATOM 2900 OEl GLU D 64 42.954 53.396 143.883 1.00 60.76 8
ATOM 2901 0E2 GLU D 64 44.416 51.734 143.493 1.00 61.33 8
ATOM 2902 C GLU D 64 46.721 56.977 144.510 1.00 52.50 6
ATOM 2903 0 GLU D 64 47.905 56.620 144.337 1.00 52.42 8
ATOM 2904 N VAL D 65 46.263 58.176 144.163 1.00 52.54 7
ATOM 2905 CA VAL D 65 47.125 59.190 143.589 1.00 52.40 6
ATOM 2906 CB VAL D 65 46.357 60.472 143.341 1.00 52.04 6
ATOM 2907 CGl VAL D 65 47.193 61.419 142.502 1.00 52.15 6
ATOM 2908 CG2 VAL D 65 45.076 60.159 142.633 1.00 52.36 6
ATOM 2909 C VAL D 65 48.324 59.474 144.487 1.00 52.53 6
ATOM 2910 0 VAL D 65 49.448 59.577 144.001 1.00 52.55 8
ATOM 2911 N LEU D 66 48.082 59.588 145.790 1.00 52.55 7
ATOM 2912 CA LEU D 66 49.143 59.858 146.743 1.00 53.00 6
ATOM 2913 CB LEU D 66 48.532 60.018 148.107 1.00 52.74 6
ATOM 2914 CG LEU D 66 47.829 61.338 148.317 1.00 53.72 6
ATOM 2915 CDl LEU D 66 46.841 61.194 149.482 1.00 55.52 6
ATOM 2916 CD2 LEU D 66 48.835 62.454 148.564 1.00 52.65 6
ATOM 2917 C LEU D 66 50.176 58.735 146.799 1.00 53.53 6
ATOM 2918 0 LEU D 66 51.393 58.957 146.875 1.00 53.43 8
ATOM 2919 N LEU D 67 49.665 57.513 146.770 1.00 53.94 7
ATOM 2920 CA LEU D 67 50.513 56.359 146.841 1.00 54.00 6
ATOM 2921 CB LEU D 67 49.678 55.106 147.103 1.00 54.17 6
ATOM 2922 CG LEU D 67 48.995 55.003 148.479 1.00 54.11 6
ATOM 2923 CDl LEU D 67 47.983 53.882 148.478 1.00 54.74 6
ATOM 2924 CD2 LEU D 67 49.991 54.797 149.624 1.00 54.00 6
ATOM 2925 C LEU D 67 51.307 56.268 145.558 1.00 54.02 6
ATOM 2926 0 LEU D 67 52.473 55.913 145.612 1.00 54.06 8
ATOM 2927 N LYS D 68 50.679 56.622 144.428 1.00 54.02 7
ATOM 2928 CA LYS D 68 51.336 56.647 143.118 1.00 54.25 6
ATOM 2929 CB LYS D 68 50.390 57.142 142.022 1.00 54.43 6
ATOM 2930 CG LYS D 68 49.465 56.086 141.426 1.00 55.79 6
ATOM 2931 CD LYS D 68 48.256 56.748 140.659 1.00 56.44 6
ATOM 2932 CE LYS D 68 47.367 55.737 139.825 1.00 57.51 6
ATOM 2933 NZ LYS D 68 46.472 54.817 140.634 1.00 57.53 7
ATOM 2934 C LYS D 68 52.526 57.565 143.160 1.00 53.49 6
ATOM 2935 0 LYS D 68 53.503 57.319 142.492 1.00 53.46 8
ATOM 2936 N HIS D 69 52.438 58.625 143.952 1.00 53.09 7
ATOM 2937 CA HIS D 69 53.504 59.614 144.009 1.00 52.93 6
ATOM 2938 CB HIS D 69 52.931 61.029 143.973 1.00 53.08 6
ATOM 2939 CG HIS D 69 52.352 61.391 142.650 1.00 53.21 6
ATOM 2940 NDl HIS D 69 53.114 61.461 141.506 1.00 53.80 7
ATOM 2941 CEI HIS D 69 52.343 61.772 140.481 1.00 53.87 6
ATOM 2942 NE2 HIS D 69 51.104 61.892 140.919 1.00 54.69 7
ATOM 2943 CD2 HIS D 69 51.083 61.660 142.274 1.00 54.11 6
ATOM 2944 C HIS D 69 54.387 59.398 145.225 1.00 52.81 6
ATOM 2945 0 HIS D 69 55.193 60.258 145.610 1.00 52.71 8
ATOM 2946 N GLY D 70 54.204 58.237 145.835 1.00 52.60 7
ATOM 2947 CA GLY D 70 55.108 57.749 146.853 1.00 52.10 6
ATOM 2948 C GLY D 70 54.890 58.330 148.222 1.00 51.92 6
ATOM 2949 0 GLY D 70 55.850 58.600 148.922 1.00 52.00 8
ATOM 2950 N ALA D 71 53.635 58.531 148.615 1.00 51.78 7
ATOM 2951 CA ALA D 71 53.336 58.858 150.004 1.00 51.36 6 ATOM 2952 CB ALA D 71 51.844 59.052 150.195 1.00 51.20 6
ATOM 2953 C ALA D 71 53.832 57.700 150.858 1.00 51.12 6
ATOM 2954 O ALA D 71 53.669 56.542 150.476 1.00 51.47 8
ATOM 2955 N ASP D 72 54.465 57.997 151.987 1.00 50.60 7
ATOM 2956 CA ASP D 72 54.756 56.961 152.970 1.00 50.14 6
ATOM 2957 CB ASP D 72 55.608 57.529 154.093 1.00 50.09 6
ATOM 2958 CG ASP D 72 55.697 56.599 155.271 1.00 51.04 6
ATOM 2959 ODl ASP D 72 54.796 55.751 155.420 1.00 52.00 8
ATOM 2960 OD2 ASP D 72 56.671 56.693 156.045 1.00 52.95 8
ATOM 2961 C ASP D 72 53.450 56.360 153.535 1.00 49.61 6
ATOM 2962 O ASP D 72 52.676 57.051 154.208 1.00 49.73 8
ATOM 2963 N VAL D 73 53.217 55.077 153.266 1.00 48.82 7
ATOM 2964 CA VAL D 73 51.958 54.439 153.652 1.00 48.30 6
ATOM 2965 CB VAL D 73 51.732 53.077 152.950 1.00 48.21 6
ATOM 2966 CGl VAL D 73 52.632 52.002 153.532 1.00 47.33 6
ATOM 2967 CG2 VAL D 73 50.278 52.653 153.073 1.00 47.25 6
ATOM 2968 C VAL D 73 51.809 54.244 155.158 1.00 48.27 6
ATOM 2969 0 VAL D 73 50.706 54.279 155.681 1.00 48.46 8
ATOM 2970 N ASN D 74 52.915 54.013 155.848 1.00 48.08 7
ATOM 2971 CA ASN D 74 52.874 53.768 157.288 1.00 47.92 6
ATOM 2972 CB ASN D 74 53.873 52.686 157.667 1.00 48.30 6
ATOM 2973 CG ASN D 74 53.529 51.373 157.083 1.00 48.84 6
ATOM 2974 ODl ASN D 74 52.379 50.958 157.106 1.00 51.13 8
ATOM 2975 ND2 ASN D 74 54.521 50.702 156.540 1.00 49.72 7
ATOM 2976 C ASN D 74 53.184 55.019 158.102 1.00 47.63 6
ATOM 2977 O ASN D 74 53.726 54.936 159.221 1.00 47.50 8
ATOM 2978 N ALA D 75 52.866 56.178 157.540 1.00 46.96 7
ATOM 2979 CA ALA D 75 53.193 57.397 158.215 1.00 46.80 6
ATOM 2980 CB ALA D 75 52.831 58.567 157.342 1.00 46.83 6
ATOM 2981 C ALA D 75 52.403 57.393 159.513 1.00 46.91 6
ATOM 2982 O ALA D 75 51.207 57.064 159.490 1.00 47.21 8
ATOM 2983 N HIS D 76 53.077 57.688 160.633 1.00 46.60 7
ATOM 2984 CA HIS D 76 52.419 57.883 161.926 1.00 46.36 6
ATOM 2985 CB HIS D 76 53.392 57.508 163.031 1.00 46.65 6
ATOM 2986 CG HIS D 76 53.740 56.055 163.071 1.00 48.58 6
ATOM 2987 NDl HIS D 76 53.021 55.135 163.807 1.00 50.60 7
ATOM 2988 CEI HIS D 76 53.551 53.933 163.661 1.00 49.68 6
ATOM 2989 NE2 HIS D 76 54.590 54.038 162.854 1.00 51.06 7
ATOM 2990 CD2 HIS D 76 54.733 55.356 162.474 1.00 50.44 6
ATOM 2991 C HIS D 76 52.033 59.364 162.068 1.00 45.97 6
ATOM 2992 O HIS D 76 52.771 60.222 161.613 1.00 45.86 8
ATOM 2993 N ASP D 77 50.885 59.690 162.667 1.00 45.68 7
ATOM 2994 CA ASP D 77 50.619 61.100 163.054 1.00 45.23 6
ATOM 2995 CB ASP D 77 49.129 61.412 163.245 1.00 45.55 6
ATOM 2996 CG ASP D 77 48.507 60.627 164.409 1.00 48.44 6
ATOM 2997 ODl ASP D 77 49.190 59.684 164.885 1.00 51.41 8
ATOM 2998 OD2 ASP D 77 47.347 60.922 164.848 1.00 50.65 8
ATOM 2999 C ASP D 77 51.371 61.240 164.346 1.00 44.37 6
ATOM 3000 0 ASP D 77 52.162 60.369 164.667 1.00 44.16 8
ATOM 3001 N ASN D 78 51.156 62.292 165.118 1.00 43.90 7
ATOM 3002 CA ASN D 78 51.989 62.401 166.343 1.00 43.50 6
ATOM 3003 CB ASN D 78 52.547 63.819 166.645 1.00 43.72 6
ATOM 3004 CG ASN D 78 51.574 64.922 166.295 1.00 45.22 6
ATOM 3005 ODl ASN D 78 51.854 66.108 166.466 1.00 44.24 8
ATOM 3006 ND2 ASN D 78 50.399 64.528 165.812 1.00 49.16 7
ATOM 3007 C ASN D 78 51.416 61.709 167.552 1.00 42.45 6 ATOM 3008 O ASN D 78 52.060 61.656 168.579 00 42.53
ATOM 3009 N ASP D 79 50.233 61.139 167.389 00 41.68 7
ATOM 3010 CA ASP D 79 49.670 60.209 168.346 00 41.40 6
ATOM 3011 CB ASP D 79 48.182 60.472 168.500 00 41.62 6
ATOM 3012 CG ASP D 79 47.888 61.535 169.535 00 43.66 6
ATOM 3013 ODl ASP D 79 48.727 61.741 170.429 00 45.21
ATOM 3014 OD2 ASP D 79 46.810 62.165 169.477 00 47.28
ATOM 3015 C ASP D 79 49.899 58.770 167.903 00 41.08
ATOM 3016 O ASP D 79 49.467 57.831 168.576 00 41.15
ATOM 3017 N GLY D 80 50.552 58.601 166.752 00 40.54 7
ATOM 3018 CA GLY D 80 50.996 57.294 166.299 00 39.71 6
ATOM 3019 C GLY D 80 50.060 56.566 165.382 00 39.20 6
ATOM 3020 O GLY D 80 50.347 55.449 164.991 1.00 39.64
ATOM 3021 N SER D 81 48.940 57.176 165.033 1.00 38.75 7
ATOM 3022 CA SER D 81 47.964 56.516 164.162 1.00 38.59 6
ATOM 3023 CB SER D 81 46.602 57.193 164.241 1.00 39.27 6
ATOM 3024 OG SER D 81 46.353 57.795 165.520 1.00 41.92
ATOM 3025 C SER D 81 48.420 56.583 162.738 1.00 37.93
ATOM 3026 O SER D 81 48.828 57.630 162.270 1.00 37.74
ATOM 3027 N THR D 82 48.364 55.453 162.055 1.00 37.77 7
ATOM 3028 CA THR D 82 48.639 55.399 160.623 .00 37.54 6
ATOM 3029 CB THR D 82 49.116 54.041 160.249 .00 37.08 6
ATOM 3030 OGl THR D 82 47.991 53.158 160.272 .00 37.19 8
ATOM 3031 CG2 THR D 82 50.154 53.580 161.237 .00 36.45 6
ATOM 3032 C THR D 82 47.351 55.645 159, 815 .00 38.09 6
ATOM 3033 O THR D 82 46.215 55.645 160, 374 .00 38.23
ATOM 3034 N PRO D 83 47.498 55.881 158.495 .00 38.05 7
ATOM 3035 CA PRO D 83 46.265 55.952 157.700 00 38.02 6
ATOM 3036 CB PRO D 83 46.782 56.078 156.272 00 38.07 6
ATOM 3037 CG PRO D 83 48.092 56.784 156, 453 00 38.03 6
ATOM 3038 CD PRO D 83 48.691 56.149 157, 677 00 37.77
ATOM 3039 C PRO D 83 45.423 54.697 157, 886 00 37.86
ATOM 3040 O PRO D 83 44.215 54.808 158, 095 00 37.83
ATOM 3041 N LEU D 84 46.067 53.529 157, 879 00 37.61 7
ATOM 3042 CA LEU D 84 45.374 52.289 158, 223 00 37.48 6
ATOM 3043 CB LEU D 84 46.339 51.132 158, 394 00 37.41 6
ATOM 3044 CG LEU D 84 45.679 49.761 158 573 00 36.97 6
ATOM 3045 CDl LEU D 84 44.628 49.434 157, 529 00 35.15 6
ATOM 3046 CD2 LEU D 84 46.764 48.672 158, 576 00 39.04 6
ATOM 3047 C LEU D 84 44.486 52.396 159, 459 00 37.59 6
ATOM 3048 O LEU D 84 43.285 52.115 159, 363 00 37.85 8
ATOM 3049 N HIS D 85 45.037 52.822 160, 599 00 37.28 7
ATOM 3050 CA HIS D 85 44.171 53.056 161, 778 00 37.54 6
ATOM 3051 CB HIS D 85 44.882 53.735 162, 947 00 38.21 6
ATOM 3052 CG HIS D 85 46.001 52.936 163, 544 00 40.87 6
ATOM 3053 NDl HIS D 85 47.314 53.057 163 124 1.00 42.17 7
ATOM 3054 CEI HIS D 85 48.077 52.245 163 835 00 42.82 6
ATOM 3055 NE2 HIS D 85 47.311 51.603 164, 703 00 43.90 7
ATOM 3056 CD2 HIS D 85 46.009 52.026 164, 550 00 43.00 6
ATOM 3057 C HIS D 85 42.971 53.908 161, 408 00 36.73 6
ATOM 3058 O HIS D 85 41.835 53.550 161, 669 00 36.06 8
ATOM 3059 N LEU D 86 43.227 55.034 160, 771 00 36.74 7
ATOM 3060 CA LEU D 86 42.134 55.950 160, 516 00 36.96 6
ATOM 3061 CB LEU D 86 42.615 57.268 159, 872 00 36.99 6
ATOM 3062 CG LEU D 86 42.840 58.501 160, 779 1.00 34.96 6
ATOM 3063 CDl LEU D 86 43.116 58.165 162, 216 1.00 32.53 6 ATOM 3064 CD2 LEU D 86 43.955 59.356 160.230 00 34.13 6
ATOM 3065 C LEU D 86 41.052 55.243 159.721 00 37.09 6
ATOM 3066 O LEU D 86 39.871 55.271 160.120 00 37.43 8
ATOM 3067 N ALA D 87 41.448 54.557 158.650 1.00 37.16 7
ATOM 3068 CA ALA D 87 40.444 53.946 157.763 .00 37.64 6
ATOM 3069 CB ALA D 87 41.076 53.314 156.536 .00 37.78 6
ATOM 3070 C ALA D 87 39.651 52.921 158.551 ,00 37.69 6
ATOM 3071 O ALA D 87 38.411 52.815 158.411 .00 37.37 8
ATOM 3072 N ALA D 88 40.376 52.201 159.410 .00 37.56 7
ATOM 3073 CA ALA D 88 39.749 51.188 160.243 1.00 37.61 6
ATOM 3074 CB ALA D 88 40.781 50.387 161.050 .00 37.41 6
ATOM 3075 C ALA D 88 38.714 51.846 161.149 .00 37.40 6
ATOM 3076 O ALA D 88 37.527 51.485 161.095 1.00 38.05
ATOM 3077 N LEU D 89 39.139 52.833 161.931 00 36.74 7
ATOM 3078 CA LEU D 89 38.235 53.494 162.842 00 36.75 6
ATOM 3079 CB LEU D 89 38.909 54.685 163.482 1.00 36.79 6
ATOM 3080 CG LEU D 89 38.059 55.434 164.505 00 36.19 6
ATOM 3081 CDl LEU D 89 37.824 54.647 165.793 00 34.74 6
ATOM 3082 CD2 LEU D 89 38.754 56.719 164.804 00 36.48
ATOM 3083 C LEU D 89 36.952 53.951 162.170 00 37.38
ATOM 3084 O LEU D 89 35.858 53.746 162.709 00 37.43
ATOM 3085 N PHE D 90 37.081 54.544 160.986 00 37.87 7
ATOM 3086 CA PHE D 90 35.917 55.046 160.280 1.00 38.27 6
ATOM 3087 CB PHE D 90 36.303 56.278 159.496 1.00 38.20 6
ATOM 3088 CG PHE D 90 36.814 57.400 160.359 1.00 39.63 6
ATOM 3089 CDl PHE D 90 38.054 57.992 160.105 1 .00 40.65 6
ATOM 3090 CEI PHE D 90 38.531 59.042 160.897 1.00 39.96 6
ATOM 3091 CZ PHE D 90 37.777 59.493 161.969 1.00 39.62 6
ATOM 3092 CE2 PHE D 90 36.535 58.909 162.241 1.00 39.71 6
ATOM 3093 CD2 PHE D 90 36.063 57.869 161.436 1.00 40.30 6
ATOM 3094 C PHE D 90 35.244 54.016 159.380 1.00 38.64 6
ATOM 3095 O PHE D 90 34.197 54.301 158.790 1.00 39.21 8
ATOM 3096 N GLY D 91 35.836 52.828 159.274 1.00 38.84 7
ATOM 3097 CA GLY D 91 35.289 51.769 158.433 1.00 39.45 6
ATOM 3098 C GLY D 91 35.266 52.052 156.937 1.00 40.00 6
ATOM 3099 O GLY D 91 34.398 51.577 156.229 1.00 39.86 8
ATOM 3100 N HIS D 92 36.220 52.834 156.461 ,00 40.94 7
ATOM 3101 CA HIS D 92 36.468 52.984 155.037 .00 42.19 6
ATOM 3102 CB HIS D 92 37.366 54.189 154.806 .00 42.71 6
ATOM 3103 CG HIS D 92 36.897 55.458 155.462 ,00 43.31 6
ATOM 3104 NDl HIS D 92 35.574 55.849 155.490 ,00 43.59 7
ATOM 3105 CEI HIS D 92 35.477 57.024 156.089 1.00 42.74 6
ATOM 3106 NE2 HIS D 92 36.690 57.417 156.436 00 41.57 7
ATOM 3107 CD2 HIS D 92 37.595 56.458 156.059 00 42.53 6
ATOM 3108 C HIS D 92 37.166 51.737 154.460 00 42.99 6
ATOM 3109 O HIS D 92 38.397 51.701 154.299 00 42.57 8
ATOM 3110 N LEU D 93 36.351 50.727 154.156 00 44.14 7
ATOM 3111 CA LEU D 93 36.795 49.395 153.731 00 45.21 6
ATOM 3112 CB LEU D 93 35.558 48.545 153.413 00 44.98 6
ATOM 3113 CG LEU D 93 34.916 47.793 154.584 00 46.49 6
ATOM 3114 CDl LEU D 93 35.654 46.509 154.779 00 48.48 6
ATOM 3115 CD2 LEU D 93 34.850 48.546 155.950 00 47.77 6
ATOM 3116 C LEU D 93 37.727 49.446 152.516 1.00 45.79 6
ATOM 3117 O LEU D 93 38.927 49.136 152.619 .00 45.73 8
ATOM 3118 N GLU D 94 37.168 49.864 151.379 .00 46.38 7
ATOM 3119 CA GLU D 94 37.913 49.977 150.137 1.00 47.32 6 ATOM 3120 CB GLU D 94 37.209 50.875 149.123 1.00 47.87
ATOM 3121 CG GLU D 94 35.773 50.480 148.792 1.00 50.66
ATOM 3122 CD GLU D 94 34.732 51.000 149.811 1.00 54.51
ATOM 3123 OEl GLU D 94 35.085 51.411 150.978 1.00 55.30
ATOM 3124 OE2 GLU D 94 33.541 50.987 149.409 1.00 54.82
ATOM 3125 C GLU D 94 39.265 50.566 150.401 1.00 47.27
ATOM 3126 O GLU D 94 40.253 50.051 149.909 1.00 47.63
ATOM 3127 N ILE D 95 39.325 51.642 151.181 1.00 47.25 7
ATOM 3128 CA ILE D 95 40.631 52.247 151.471 1.00 46.95 6
ATOM 3129 CB ILE D 95 40.528 53.622 152.125 .00 46.49 6
ATOM 3130 CGl ILE D 95 39.704 54.544 151.232 .00 47.00 6
ATOM 3131 CD ILE D 95 40.035 56.039 151.322 1.00 48.34 6
ATOM 3132 CG2 ILE D 95 41.903 54.159 152.380 .00 44.86 6
ATOM 3133 C ILE D 95 41.566 51.319 152.273 .00 47.05 6
ATOM 3134 O ILE D 95 42.729 51.117 151.899 .00 46.91 8
ATOM 3135 N VAL D 96 41.055 50.742 153.354 .00 46.95 7
ATOM 3136 CA VAL D 96 41.851 49.807 154.114 1.00 47.05 6
ATOM 3137 CB VAL D 96 41.031 49.076 155.184 .00 46.86 6
ATOM 3138 CGl VAL D 96 41.793 47.913 155.710 ,00 46.56 6
ATOM 3139 CG2 VAL D 96 40.733 49.989 156.328 1.00 47.17 6
ATOM 3140 C VAL D 96 42.474 48.807 153.144 00 47.44 6
ATOM 3141 0 VAL D 96 43.675 48.499 153.229 00 47.52 8
ATOM 3142 N GLU D 97 41.671 48.319 152.199 1.00 47.60 7
ATOM 3143 CA GLU D 97 42.181 47.344 151.253 00 47.52 6
ATOM 3144 CB GLU D 97 41.073 46.733 150.430 00 47.27 6
ATOM 3145 CG GLU D 97 41.194 45.235 150.425 1.00 50.37
ATOM 3146 CD GLU D 97 39.832 44.502 150.587 1 .00 55.38
ATOM 3147 OEl GLU D 97 38.785 45.211 150.696 1.00 56.20
ATOM 3148 0E2 GLU D 97 39.812 43.220 150.609 1.00 55.45
ATOM 3149 C GLU D 97 43.302 47.945 150.411 1.00 47.00
ATOM 3150 0 GLU D 97 44.446 47.523 150.532 1.00 47.32
ATOM 3151 N VAL D 98 43.021 48.975 149.628 1.00 46.38 7
ATOM 3152 CA VAL D 98 44.094 49.545 148.812 1.00 46.13 6
ATOM 3153 CB VAL D 98 43.635 50.735 147.907 1.00 45.79 6
ATOM 3154 CGl VAL D 98 42.442 51.371 148.476 00 45.71 6
ATOM 3155 CG2 VAL D 98 44.743 51.749 147.692 00 44.99 6
ATOM 3156 C VAL D 98 45.351 49.845 149.643 00 46.05 6
ATOM 3157 0 VAL D 98 46.478 49.618 149.170 1.00 46.27 8
ATOM 3158 N LEU D 99 45.166 50.314 150.876 00 45.49 7
ATOM 3159 CA LEU D 99 46.320 50.560 151.757 00 45.07 6
ATOM 3160 CB LEU D 99 45.876 51.144 153.102 1.00 44.73 6
ATOM 3161 CG LEU D 99 45.508 52.622 153.075 1.00 43.54 6
ATOM 3162 CDl LEU D 99 44.580 52.958 154.231 1.00 44.41 6
ATOM 3163 CD2 LEU D 99 46.762 53.445 153.158 1.00 42.12 6
ATOM 3164 C LEU D 99 47.149 49.283 151.958 1.00 44.90 6
ATOM 3165 0 LEU D 99 48.377 49.258 151.774 1.00 44.16
ATOM 3166 N LEU D 100 46.442 48.219 152.305 1.00 44.97 7
ATOM 3167 CA LEU D 100 47.074 46.956 152.548 1.00 45.14 6
ATOM 3168 CB LEU D 100 46.018 45.915 152.916 1 .00 44.84 6
ATOM 3169 CG LEU D 100 45.452 46.176 154.310 1.00 44.24 6
ATOM 3170 CDl LEU D 100 44.266 45.300 154.603 1.00 43.26 6
ATOM 3171 CD2 LEU D 100 46.552 46.013 155.385 1.00 43.69
ATOM 3172 C LEU D 100 47.826 46.599 151.301 1.00 45.54
ATOM 3173 0 LEU D 100 49.012 46.298 151.363 1.00 44.84
ATOM 3174 N LYS D 101 47.117 46.699 150.177 1.00 46.62 7
ATOM 3175 CA LYS D 101 47.627 46.356 148.877 1.00 47.97 6 ATOM 3176 CB LYS D 101 46.657 46.811 147.780 1.00 48.24 6
ATOM 3177 CG LYS D 101 46.956 46.186 146.374 1.00 51.29 6
ATOM 3178 CD LYS D 101 46.738 47.169 145.188 1.00 54.07 6
ATOM 3179 CE LYS D 101 45.236 47.457 144.939 1.00 56.15 6
ATOM 3180 NZ LYS D 101 44.935 48.939 144.795 1.00 57.79 7
ATOM 3181 C LYS D 101 48.960 47.041 148.710 1.00 48.35 6
ATOM 3182 0 LYS D 101 49.917 46.452 148.233 1.00 48.54 8
ATOM 3183 N HIS D 102 49.037 48.289 149.126 1.00 49.10 7
ATOM 3184 CA HIS D 102 50.278 48.997 148.973 1.00 49.83 6
ATOM 3185 CB HIS D 102 50.026 50.453 148.615 1.00 50.28 6
ATOM 3186 CG HIS D 102 49.568 50.634 147.207 1.00 52.47 6
ATOM 3187 NDl HIS D 102 49.607 51.849 146.560 1.00 54.04 7
ATOM 3188 CEI HIS D 102 49.133 51.707 145.334 1.00 55.43 6
ATOM 3189 NE2 HIS D 102 48.813 50.435 145.156 1.00 56.22 7
ATOM 3190 CD2 HIS D 102 49.080 49.741 146.310 1.00 54.07 6
ATOM 3191 C HIS D 102 51.117 48.856 150.214 1.00 49.85 6
ATOM 3192 0 HIS D 102 51.895 49.750 150.542 1.00 50.07 8
ATOM 3193 N GLY D 103 50.946 47.736 150.910 1.00 49.92 7
ATOM 3194 CA GLY D 103 51.864 47.331 151.990 1.00 49.79 6
ATOM 3195 C GLY D 103 51.776 48.053 153.329 1.00 49.60 6
ATOM 3196 0 GLY D 103 52.767 48.136 154.057 1.00 49.71 8
ATOM 3197 N ALA D 104 50.594 48.585 153.643 1.00 49.21 7
ATOM 3198 CA ALA D 104 50.295 49.116 154.959 1.00 48.27 6
ATOM 3199 CB ALA D 104 48.817 49.457 155.057 1.00 48.63 6
ATOM 3200 C ALA D 104 50.609 48.041 155.938 1.00 47.70 6
ATOM 3201 0 ALA D 104 50.172 46.904 155.778 1.00 47.90 8
ATOM 3202 N ASP D 105 51.378 48.393 156.947 1.00 47.30 7
ATOM 3203 CA ASP D 105 51.674 47.449 158.009 1.00 47.43 6
ATOM 3204 CB ASP D 105 52.836 47.943 158.859 1.00 47.65 6
ATOM 3205 CG ASP D 105 53.146 46.995 159.980 1.00 49.35 6
ATOM 3206 ODl ASP D 105 52.416 45.990 160.093 1.00 52.31 8
ATOM 3207 0D2 ASP D 105 54.101 47.236 160.747 1.00 50.89 8
ATOM 3208 C ASP D 105 50.454 47.179 158.902 1.00 46.81 6
ATOM 3209 0 ASP D 105 50.028 48.051 159.658 1.00 47.03 8
ATOM 3210 N VAL D 106 49.908 45.971 158.829 1.00 45.98 7
ATOM 3211 CA VAL D 106 48.718 45.650 159.603 1.00 45.54 6
ATOM 3212 CB VAL D 106 48.139 44.282 159.178 1.00 45.57 6
ATOM 3213 CGl VAL D 106 49.185 43.177 159.333 1.00 45.17 6
ATOM 3214 CG2 VAL D 106 46.848 43.957 159.943 1.00 44.74 6
ATOM 3215 C VAL D 106 49.037 45.659 161.105 1.00 45.38 6
ATOM 3216 0 VAL D 106 48.164 45.842 161.959 1.00 46.00 8
ATOM 3217 N ASN D 107 50.305 45.468 161.411 1.00 44.44 7
ATOM 3218 CA ASN D 107 50.727 45.272 162.769 1.00 43.82 6
ATOM 3219 CB ASN D 107 51.978 44.409 162.790 1.00 43.96 6
ATOM 3220 CG ASN D 107 51.667 42.965 162.783 1.00 43.63 6
ATOM 3221 ODl ASN D 107 50.552 42.559 163.102 1.00 45.40 8
ATOM 3222 ND2 ASN D 107 52.645 42.167 162.437 1.00 42.98 7
ATOM 3223 C ASN D 107 51.070 46.553 163.438 1.00 43.38 6
ATOM 3224 0 ASN D 107 51.303 46.562 164.643 1.00 43.78 8
ATOM 3225 N ALA D 108 51.149 47.622 162.654 1.00 42.64 7
ATOM 3226 CA ALA D 108 51.585 48.921 163.145 1.00 41.86 6
ATOM 3227 CB ALA D 108 51.520 49.926 162.033 1.00 41.89 6
ATOM 3228 C ALA D 108 50.684 49.337 164.275 1.00 41.55 6
ATOM 3229 0 ALA D 108 49.448 49.162 164.186 1.00 41.65 8
ATOM 3230 N GLN D 109 51.286 49.864 165.344 1.00 41.02 7
ATOM 3231 CA GLN D 109 50.483 50.349 166.484 1.00 40.85 6 ATOM 3232 CB GLN D 109 50.621 49.461 167.717 00 40.51 6
ATOM 3233 CG GLN D 109 51.932 48.751 167.878 00 40.99 6
ATOM 3234 CD GLN D 109 52.040 48.087 169.243 00 41.68 6
ATOM 3235 OEl GLN D 109 52.939 48.401 170.005 00 42.71 8
ATOM 3236 NE2 GLN D 109 51.097 47.199 169.575 00 42.04 7
ATOM 3237 C GLN D 109 50.641 51.825 166.851 00 40.50 6
ATOM 3238 O GLN D 109 51.721 52.374 166.752 00 40.77
ATOM 3239 N ASP D 110 49.548 52.461 167.260 00 40.06 7
ATOM 3240 CA ASP D 110 49.587 53.849 167.666 00 39.99 6
ATOM 3241 CB ASP D 110 48.196 54.441 167.600 00 40.69
ATOM 3242 CG ASP D 110 47.228 53.757 168.554 00 42.12
ATOM 3243 ODl ASP D 110 47.674 53.154 169.561 00 42.18
ATOM 3244 0D2 ASP D 110 46.009 53.833 168.298 00 44.73
ATOM 3245 C ASP D 110 50.067 53.888 169.091 00 39.64
ATOM 3246 0 ASP D 110 50.463 52.859 169.637 00 39.93
ATOM 3247 N LYS D 111 49.977 55.053 169.722 00 39.12 7
ATOM 3248 CA LYS D 111 50.610 55.272 171.027 1.00 38.69 6
ATOM 3249 CB LYS D 111 50.677 56.767 171.365 00 38.75 6
ATOM 3250 CG LYS D 111 49.407 57.380 171.880 00 38.85 6
ATOM 3251 CD LYS D 111 49.560 58.871 172.150 1.00 39.40 6
ATOM 3252 CE LYS D 111 48.660 59.273 173.329 1.00 41.93 6
ATOM 3253 NZ LYS D 111 48.289 60.728 173.381 1.00 43.00 7
ATOM 3254 C LYS D 111 49.991 54.504 172.172 1.00 38.32 6
ATOM 3255 0 LYS D 111 50.566 54.449 173.241 1.00 38.35 8
ATOM 3256 N PHE D 112 48.811 53.930 171.947 1.00 38.20 7
ATOM 3257 CA PHE D 112 48.149 53.047 172.912 1.00 37.90 6
ATOM 3258 CB PHE D 112 46.650 53.254 172.835 1.00 37.59 6
ATOM 3259 CG PHE D 112 46.236 54.650 173.009 1.00 38.01 6
ATOM 3260 CDl PHE D 112 45.931 55.138 174.267 1.00 38.14 6
ATOM 3261 CEI PHE D 112 45.527 56.467 174.430 1.00 38.84 6
ATOM 3262 CZ PHE D 112 45.429 57.328 173.323 1.00 38.07 6
ATOM 3263 CE2 PHE D 112 45.722 56.850 172.063 00 38.90 6
ATOM 3264 CD2 PHE D 112 46.124 55.498 171.904 00 39.25 6
ATOM 3265 C PHE D 112 48.432 51.575 172.590 1.00 37.78 6
ATOM 3266 0 PHE D 112 47.815 50.666 173.137 1.00 37.67 8
ATOM 3267 N GLY D 113 49.332 51.341 171.652 1.00 37.75 7
ATOM 3268 CA GLY D 113 49.599 49.997 171.200 00 37.64 6
ATOM 3269 C GLY D 113 48.435 49.293 170.528 ,00 37.60 6
ATOM 3270 0 GLY D 113 48.449 48.061 170.443 00 38.12 8
ATOM 3271 N LYS D 114 47.436 50.040 170.049 00 37.15 7
ATOM 3272 CA LYS D 114 46.343 49.433 169.285 ,00 36.68 6
ATOM 3273 CB LYS D 114 45.053 50.239 169.374 00 36.20 6
ATOM 3274 CG LYS D 114 44.621 50.644 170.746 ,00 34.82 6
ATOM 3275 CD LYS D 114 43.126 50.756 170.808 00 31.61 6
ATOM 3276 CE LYS D 114 42.525 49.461 171.278 00 30.65 6
ATOM 3277 NZ LYS D 114 42.300 49.489 172.731 ,00 31.39 7
ATOM 3278 C LYS D 114 46.728 49.385 167.835 00 37.20 6
ATOM 3279 0 LYS D 114 47.293 50.332 167.303 00 37.31 8
ATOM 3280 N THR D 115 46.404 48.277 167.190 ,00 38.07 7
ATOM 3281 CA THR D 115 46.512 48.164 165.730 00 38.81 6
ATOM 3282 CB THR D 115 47.098 46.797 165.282 ,00 39.00 6
ATOM 3283 OGl THR D 115 46.073 45.782 165.327 00 38.89
ATOM 3284 CG2 THR D 115 48.278 46.395 166.150 00 38.82 6
ATOM 3285 C THR D 115 45.126 48.293 165.082 ,00 39.25 6
ATOM 3286 0 THR D 115 44.063 48.239 165.761 00 39.14
ATOM 3287 N ALA D 116 45.133 48.433 163.760 1.00 39.29 ATOM 3288 CA ALA D 116 43.871 48.480 163.051 .00 39.43
ATOM 3289 CB ALA D 116 44.100 48.402 161.581 ,00 39.57 6
ATOM 3290 C ALA D 116 42.962 47.341 163.529 ,00 39.35 6
ATOM 3291 0 ALA D 116 41.785 47.556 163.872 ,00 39.21
ATOM 3292 N PHE D 117 43.529 46.143 163.602 .00 39.13 7
ATOM 3293 CA PHE D 117 42.756 45.006 164.014 .00 39.14 6
ATOM 3294 CB PHE D 117 43.622 43.785 164.124 ,00 39.19 6
ATOM 3295 CG PHE D 117 42.847 42.559 164.482 .00 39.34 6
ATOM 3296 CDl PHE D 117 42.051 41.926 163.530 ,00 39.36 6
ATOM 3297 CEI PHE D 117 41.338 40.799 163.848 1.00 38.22 6
ATOM 3298 CZ PHE D 117 41.410 40.285 165.126 00 38.31 6
ATOM 3299 CE2 PHE D 117 42.179 40.912 166.084 00 37.14 6
ATOM 3300 CD2 PHE D 117 42.885 42.050 165.766 00 37.40 6
ATOM 3301 C PHE D 117 42.002 45.189 165.327 00 39.31 6
ATOM 3302 0 PHE D 117 40.805 44.869 165.388 1.00 39.25 8
ATOM 3303 N ASP D 118 42.676 45.687 166.369 ,00 39.30 7
ATOM 3304 CA ASP D 118 41.955 45.995 167.609 .00 39.79 6
ATOM 3305 CB ASP D 118 42.823 46.614 168.685 ,00 40.66 6
ATOM 3306 CG ASP D 118 44.248 46.129 168.638 1.00 43.93
ATOM 3307 ODl ASP D 118 44.709 45.438 169.599 1.00 46.69
ATOM 3308 0D2 ASP D 118 44.905 46.448 167.623 1.00 46.66
ATOM 3309 C ASP D 118 40.834 46.964 167.314 1.00 39.28
ATOM 3310 0 ASP D 118 39.685 46.656 167.624 1.00 39.00
ATOM 3311 N ILE D 119 41.165 48.111 166.695 1 ,00 38.74 7
ATOM 3312 CA ILE D 119 40.158 49.134 166.348 1.00 38.04 6
ATOM 3313 CB ILE D 119 40.655 50.167 165.331 1.00 37.88 6
ATOM 3314 CGl ILE D 119 41.790 50.981 165.904 00 37.76 6
ATOM 3315 CD ILE D 119 42.035 52.231 165.105 1.00 39.40 6
ATOM 3316 CG2 ILE D 119 39.563 51.122 164.936 .00 36.31 6
ATOM 3317 C ILE D 119 38.918 48.476 165.773 .00 38.04 6
ATOM 3318 O ILE D 119 37.818 48.756 166.251 1.00 37.85
ATOM 3319 N SER D 120 39.102 47.594 164.783 00 38.01 7
ATOM 3320 CA SER D 120 37.981 46.879 164.149 00 38.88 6
ATOM 3321 CB SER D 120 38.455 45.917 163.061 1.00 38.86 6
ATOM 3322 OG SER D 120 39.324 44.953 163.615 00 40.23
ATOM 3323 C SER D 120 37.163 46.086 165.152 00 39.11
ATOM 3324 O SER D 120 35.920 46.130 165.142 00 39.19
ATOM 3325 N ILE D 121 37.860 45.359 166.020 00 39.36 7
ATOM 3326 CA ILE D 121 37.187 44.658 167.108 00 39.54 6
ATOM 3327 CB ILE D 121 38.147 43.791 167.947 00 39.27 6
ATOM 3328 CGl ILE D 121 38.940 42.817 167.067 00 39.46 6
ATOM 3329 CD ILE D 121 38.308 41.475 166.842 00 39.04 6
ATOM 3330 CG2 ILE D 121 37.380 43.063 169.017 00 38.50 6
ATOM 3331 C ILE D 121 36.497 45.648 168.042 00 40.04 6
ATOM 3332 0 ILE D 121 35.374 45.421 168.424 00 40.19 8
ATOM 3333 N ASP D 122 37.172 46.742 168.390 00 40.72 7
ATOM 3334 CA ASP D 122 36.672 47.688 169.376 00 41.41 6
ATOM 3335 CB ASP D 122 37.685 48.782 169.650 00 41.82 6
ATOM 3336 CG ASP D 122 38.892 48.278 170.407 1.00 44.06 6
ATOM 3337 ODl ASP D 122 38.835 47.186 171.051 ,00 45.13
ATOM 3338 0D2 ASP D 122 39.911 48.993 170.342 ,00 46.51
ATOM 3339 C ASP D 122 35.407 48.339 168.934 .00 41.66
ATOM 3340 0 ASP D 122 34.514 48.571 169.741 1.00 42.06
ATOM 3341 N ASN D 123 35.295 48.665 167.662 ,00 42.04 7
ATOM 3342 CA ASN D 123 34.003 49.166 167.261 .00 42.54 6
ATOM 3343 CB ASN D 123 34.075 50.565 166.638 1.00 42.09 6 ATOM 3344 CG ASN D 123 35.046 50.646 165.537 00 41.28
ATOM 3345 ODl ASN D 123 35.365 49.636 164.930 00 41.88
ATOM 3346 ND2 ASN D 123 35.524 51.844 165.249 00 39.46 7
ATOM 3347 C ASN D 123 33.222 48.132 166.464 00 43.06 6
ATOM 3348 0 ASN D 123 32.422 48.466 165.602 00 43.33 8
ATOM 3349 N GLY D 124 33.466 46.867 166.789 00 43.87 7
ATOM 3350 CA GLY D 124 32.633 45.741 166.348 00 45.09 6
ATOM 3351 C GLY D 124 32.368 45.593 164.858 00 45.73 6
ATOM 3352 0 GLY D 124 31.375 45.019 164.455 00 45.73
ATOM 3353 N ASN D 125 33.251 46.128 164.038 1.00 46.74 7
ATOM 3354 CA ASN D 125 33.127 45.991 162.611 1.00 47.72 6
ATOM 3355 CB ASN D 125 33.801 47.166 161.910 1.00 47.53 6
ATOM 3356 CG ASN D 125 33.739 47.066 160.416 1.00 46.64
ATOM 3357 ODl ASN D 125 33.200 46.121 159.872 1.00 46.94
ATOM 3358 ND2 ASN D 125 34.294 48.047 159.741 1.00 46.95 7
ATOM 3359 C ASN D 125 33.784 44.701 162.215 1.00 48.87 6
ATOM 3360 0 ASN D 125 34.970 44.667 161.901 1.00 49.09
ATOM 3361 N GLU D 126 32.992 43.639 162.238 1 .00 50.50 7
ATOM 3362 CA GLU D 126 33.447 42.277 161.980 1.00 52.59 6
ATOM 3363 CB GLU D 126 32.290 41.321 162.268 1.00 52.18 6
ATOM. 3364 CG GLU D 126 32.679 39.846 162.309 1.00 54.34
ATOM 3365 CD GLU D 126 31.454 38.932 162.234 00 55.49
ATOM 3366 OEl GLU D 126 31.509 37.855 161.569 00 58.43
ATOM 3367 0E2 GLU D 126 30.416 39.306 162.841 00 59.24
ATOM 3368 C GLU D 126 33.951 42.045 160.550 1.00 52.89
ATOM 3369 0 GLU D 126 34.895 41.287 160.333 00 53.13
ATOM 3370 N ASP D 127 33.294 42.676 159.578 00 53.67 7
ATOM 3371 CA ASP D 127 33.741 42.651 158.185 00 54.21 6
ATOM 3372 CB ASP D 127 32.923 43.612 157.337 1.00 54.22
ATOM 3373 CG ASP D 127 31.630 43.013 156.867 1.00 55.59
ATOM 3374 ODl ASP D 127 31.512 41.772 156.897 1.00 58.23
ATOM 3375 0D2 ASP D 127 30.722 43.770 156.457 1.00 56.87
ATOM 3376 C ASP D 127 35.191 43.043 158.060 1.00 54.52
ATOM 3377 0 ASP D 127 35.989 42.266 157.555 1 00 55.01
ATOM 3378 N LEU D 128 35.516 44.253 158.515 1 00 54.66 7
ATOM 3379 CA LEU D 128 36.875 44.754 158.558 1 00 54.89 6
ATOM 3380 CB LEU D 128 36.942 46.009 159.399 1 00 55.14 6
ATOM 3381 CG LEU D 128 38.054 47.049 159.209 1 00 55.58 6
ATOM 3382 CDl LEU D 128 38.414 47.709 160.527 1 00 54.76 6
ATOM 3383 CD2 LEU D 128 39.286 46.495 158.561 1 00 56.13 6
ATOM 3384 C LEU D 128 37.792 43.755 159.206 1 00 55.21 6
ATOM 3385 0 LEU D 128 38.806 43.390 158.628 1 00 55.31 8
ATOM 3386 N ALA D 129 37.438 43.323 160.413 1 00 55.68 7
ATOM 3387 CA ALA D 129 38.233 42.348 161.158 1 00 56.33 6
ATOM 3388 CB ALA D 129 37.463 41.856 162.340 1 00 56.44 6
ATOM 3389 C ALA D 129 38.666 41.181 160.294 1 00 56.73 6
ATOM 3390 0 ALA D 129 39.834 40.849 160.229 1 00 56.57 8
ATOM 3391 N GLU D 130 37.697 40.595 159.612 1 00 57.71 7
ATOM 3392 CA GLU D 130 37.891 39.482 158.699 1 00 58.84 6
ATOM 3393 CB GLU D 130 36.549 39.088 158.086 1 00 58.91 6
ATOM 3394 CG GLU D 130 36.326 37.580 157.875 1 00 60.78 6
ATOM 3395 CD GLU D 130 34.915 37.246 157.329 1 00 61.28 6
ATOM 3396 OEl GLU D 130 34.605 36.036 157.168 1 00 63.77
ATOM 3397 OE2 GLU D 130 34.114 38.185 157.060 1 00 63.59
ATOM 3398 C GLU D 130 38.815 39.850 157.574 1 00 58.34
ATOM 3399 0 GLU D 130 39.571 39.031 157.107 1.00 58.65 ATOM 3400 N ILE D 131 38.750 41.073 157.098 1.00 58.35 7
ATOM 3401 CA ILE D 131 39.672 41.412 156.042 1.00 58.43 6
ATOM 3402 CB ILE D 131 39.202 42.551 155.099 1.00 58.03 6
ATOM 3403 CGl ILE D 131 40.244 43.640 155.041 1.00 57.11 6
ATOM 3404 CD ILE D 131 40.041 44.549 153.922 1.00 57.22 6
ATOM 3405 CG2 ILE D 131 37.883 43.136 155.513 1.00 57.47 6
ATOM 3406 C ILE D 131 41.077 41.609 156.579 1.00 58.96 6
ATOM 3407 O ILE D 131 42.036 41.410 155.845 1.00 59.08 8
ATOM 3408 N LEU D 132 41.200 41.967 157.857 1.00 59.64 7
ATOM 3409 CA LEU D 132 42.525 42.078 158.485 1.00 60.48 6
ATOM 3410 CB LEU D 132 42.537 43.048 159.664 1.00 59.77 6
ATOM 3411 CG LEU D 132 42.123 44.505 159.427 1.00 58.68 6
ATOM 3412 CDl LEU D 132 41.962 45.279 160.734 1.00 56.21 6
ATOM 3413 CD2 LEU D 132 43.092 45.215 158.517 1.00 58.25 6
ATOM 3414 C LEU D 132 43.106 40.728 158.915 1.00 61.74 6
ATOM 3415 O LEU D 132 44.325 40.564 158.889 1.00 61.96 8
ATOM 3416 N GLN D 133 42.252 39.769 159.297 1.00 62.98 7
ATOM 3417 CA GLN D 133 42.714 38.421 159.632 1.00 64.24 6
ATOM 3418 CB GLN D 133 41.629 37.568 160.269 1.00 63.46 6
ATOM 3419 CG GLN D 133 40.606 38.347 161.010 1.00 63.49 6
ATOM 3420 CD GLN D 133 40.125 37.696 162.295 1.00 62.49 6
ATOM 3421 OEl GLN D 133 38.944 37.366 162.422 1.00 61.70 8
ATOM 3422 NE2 GLN D 133 41.025 37.559 163.274 1.00 61.16 7
ATOM 3423 C GLN D 133 43.196 37.722 158.391 1.00 65.87 6
ATOM 3424 0 GLN D 133 44.056 36.862 158.462 1.00 66.34 8
ATOM 3425 N LYS D 134 42.637 38.098 157.247 1.00 67.88 7
ATOM 3426 CA LYS D 134 42.958 37.479 155.968 1.00 69.45 6
ATOM 3427 CB LYS D 134 41.982 37.949 154.899 1.00 69.50 6
ATOM 3428 CG LYS D 134 40.880 36.954 154.655 1.00 69.74 6
ATOM 3429 CD LYS D 134 40.247 37.167 153.282 1.00 70.46 6
ATOM 3430 CE LYS D 134 39.081 36.219 153.101 1.00 69.53 6
ATOM 3431 NZ LYS D 134 38.315 36.185 154.378 1.00 68.46 7
ATOM 3432 C LYS D 134 44.380 37.758 155.516 1.00 70.59 6
ATOM 3433 O LYS D 134 44.776 37.378 154.419 1.00 71.05 8
ATOM 3434 N LEU D 135 45.161 38.419 156.352 1.00 71.76 7
ATOM 3435 CA LEU D 135 46.517 38.729 155.952 1.00 73.04 6
ATOM 3436 CB LEU D 135 46.817 40.200 156.190 1.00 72.80 6
ATOM 3437 CG LEU D 135 45.845 41.222 155.624 1.00 73.19 6
ATOM 3438 CDl LEU D 135 46.683 42.401 155.235 1.00 73.35 6
ATOM 3439 CD2 LEU D 135 45.045 40.723 154.417 1.00 73.25 6
ATOM 3440 C LEU D 135 47.585 37.880 156.630 1.00 73.90 6
ATOM 3441 O LEU D 135 47.401 37.401 157.750 1.00 74.12 8
ATOM 3442 N ASN D 136 48.698 37.697 155.917 1.00 74.85 7
ATOM 3443 CA ASN D 136 49.983 37.279 156.506 1.00 75.36 6
ATOM 3444 CB ASN D 136 51.157 37.643 155.572 1.00 75.34 6
ATOM 3445 CG ASN D 136 51.405 36.607 154.495 1.00 75.68 6
ATOM 3446 ODl ASN D 136 52.547 36.392 154.085 1.00 76.30 8
ATOM 3447 ND2 ASN D 136 50.343 35.961 154.026 1.00 76.17 7
ATOM 3448 C ASN D 136 50.223 37.945 157.869 1.00 75.50 6
ATOM 3449 0 ASN D 136 50.143 39.172 158.017 1.00 75.57 8
ATOM 3450 OXT ASN D 136 50.494 37.277 158.867 1.00 75.61 8
ATOM 3451 0 HOH W 1 39.138 62.572 162.958 1.00 35.50 8
ATOM 3452 0 HOH W 2 23.650 56.588 178.179 1.00 14.86 8
ATOM 3453 0 HOH W 3 29.968 72.539 172.433 1.00 39.04 8
ATOM 3454 0 HOH W 4 15.687 58.071 156.392 1.00 42.72 8
ATOM 3455 0 HOH W 5 53.222 71.911 156.097 1.00 17.44 8 ATOM 3456 0 HOH W 7 7.516 45.583 169.214 1.00 27.95 8
ATOM 3457 0 HOH W 8 21.763 70.506 166.534 1.00 52.40 8
ATOM 3458 0 HOH W 9 40.935 72.205 154.010 1.00 52.17 8
ATOM 3459 0 HOH W 10 25.966 55.823 176.389 1.00 33.09 8
ATOM 3460 0 HOH W 11 22.985 68.007 186.404 1.00 31.73 8
ATOM 3461 0 HOH W 12 19.448 80.405 148.664 1.00 55.55 8
ATOM 3462 O HOH W 13 45.407 70.720 157.818 1.00 51.51 8
ATOM 3463 O HOH W 14 63.737 34.018 250.378 1.00 32.05 8
ATOM 3464 0 HOH W 15 47.212 38.556 218.411 1.00 49.21 8
ATOM 3465 O HOH W 16 15.743 67.512 164.830 1.00 48.95 8
ATOM 3466 0 HOH W 17 22.476 54.851 168.024 1.00 38.77 8
ATOM 3467 0 HOH W 18 41.039 72.232 147.406 1.00 42.02 8
ATOM 3468 O HOH W 19 19.457 49.799 183.166 1.00 51.67 8
ATOM 3469 O HOH W 20 50.654 61.154 152.546 1.00 50.46 8
ATOM 3470 0 HOH W 21 49.970 57.246 176.606 1.00 41.58 8
ATOM 3471 0 HOH W 22 15.170 61.276 178.334 1.00 54.81 8
ATOM 3472 O HOH W 23 50.212 50.934 189.517 1.00 60.63 8
ATOM 3473 0 HOH W 24 21.739 52.101 175.735 1.00 60.72 8
ATOM 3474 0 HOH W 25 33.393 54.787 148.401 1.00 52.56 8
ATOM 3475 O HOH W 26 15.340 61.743 143.921 1.00 71.13 8
ATOM 3476 O HOH W 27 45.833 67.108 136.296 1.00 58.98 8
ATOM 3477 03 GOL W 50 44.951 55.236 166.054 1.00 42.03 8
ATOM 3478 C3 GOL W 50 43.576 55.492 166.281 1.00 44.24 6
ATOM 3479 C2 GOL W 50 43.379 55.849 167.742 1.00 46.17 6
ATOM 3480 02 GOL W 50 43.678 54.769 168.615 1.00 45.85 8
ATOM 3481 Cl GOL W 50 41.926 56.188 167.959 1.00 47.57 6
ATOM 3482 01 GOL W 50 41.639 55.649 169.238 1.00 52.52 8

Claims

REVENDICATIONS
1. Cristal du domaine CC2-LZ de NEMO de mammifère, caractérisé par la séquence d'acides aminés SEQ ID NO.3 du domaine CC2-LZ ou les variants de ladite séquence d'acides aminés.
2. Cristal du domaine CC2-LZ de NEMO de mammifère, caractérisé par la séquence d'acides aminés SEQ ID NO.4 du domaine CC2-LZ ou les variants de ladite séquence d'acides aminés.
3. Cristal du domaine CC2-LZ de NEMO de mammifère selon l'une des revendications 1 ou 2, caractérisé en ce que le cristal possède les paramètres de maille suivants : - a=b=63.5 ± 5 A ;
- c=437.5 ± 5 A ; et
- α=β=γ=90°; et en ce que le cristal a un groupe d'espace ΨA%2^λ.
4. Cristal selon la revendication 3, caractérisé en ce qu'il possède les coordonnées cristallographiques décrites dans le tableau 1.
5. Cristal selon la revendication 3, caractérisé en ce qu'il comprend le domaine CC2-LZ de NEMO de mammifère et au moins une ankyrine ou un fragment de celle-ci capable de stabiliser le complexe
6. Cristal selon la revendication 5, caractérisé en ce qu'il comprend une ankyrine 1D5.
7. Cristal selon l'une des revendications 1 à 6, caractérisé par sa structure tridimensionnelle obtenue par diffraction des rayons X, ladite structure tridimensionnelle étant représentée figures 2 et 3.
8. Cristal selon l'une des revendications 1 à 7, caractérisé en ce que la protéine
CC2-LZ comprend la mutation Ala316Pro (A316P) et/ou la mutation Phe305Ala (F305A).
9. Cristal selon l'une des revendications 2 à 7, caractérisé en ce que la protéine CC2-LZ comprend la mutation Ala323Pro (A323P) et/ou la mutation Phe312Ala
(F312A).
10. Procédé de cristallisation du domaine CC2-LZ de NEMO de mammifère, caractérisé en ce que le procédé comprend les étapes suivantes : - incubation d'au moins une ankyrine ou d'un fragment d'ankyrine et du domaine CC2-LZ ;
- co-cristallisation du complexe protéique ankyrine ou d'un fragment d'ankyrine/CC2-LZ par culture des cristaux par diffusion de vapeur.
11. Cristal produit par le procédé selon la revendication 10.
12. Structure tridimensionnelle du domaine CC2-LZ de NEMO de mammifère ayant les coordonnées cristallographiques du tableau 1.
13. Procédé de détermination de la structure tridimensionnelle du cristal du domaine CC2-LZ de NEMO selon l'une des revendications 1 à 9, caractérisé en ce que le procédé comprend les étapes suivantes :
- obtention d'un cristal de la protéine CC2-LZ ;
- exposition du cristal aux rayons X ; - collecte des données de diffraction aux rayons X ; - utilisation de ces données pour calculer la carte de densité électronique dudit cristal ;
- construction et affinement du modèle à partir de la carte de densité électronique.
14. Méthode d'identification de composés capables de se lier au domaine CC2- LZ de NEMO, caractérisée en ce qu'elle utilise les coordonnées cristallographiques obtenues à partir du cristal selon l'une des revendications 1 à 9.
15. Peptide identifié par la méthode selon la revendication 14, caractérisé en ce qu'il se lie au domaine CC2-LZ de NEMO.
16. Peptide PH4 identifié par la méthode selon la revendication 14, caractérisé par la séquence en acides aminés SEQ ID NO.6.
17. Peptide P8RD identifié par la méthode selon la revendication 14, caractérisé par la séquence en acides aminés SEQ ID NO.7.
18. Méthode d'identification de composés impliqués dans la dimérisation de
NEMO ou l'interaction de NEMO avec les chaînes polyubiquitines entre un peptide selon l'une des revendications 15 à 17 et le domaine CC2-LZ de NEMO, caractérisée en ce qu'elle comprend les étapes suivantes :
- la mise en contact dudit peptide et dudit domaine CC2-LZ de NEMO ; - l'ajout du composé à tester ;
- la mesure de la polarisation de fluorescence en présence du composé à tester ;
- la comparaison de ladite mesure en l'absence du composé à tester.
19. Méthode de conception de composés capables de se lier au domaine CC2-
LZ de NEMO, caractérisée en ce qu'elle utilise la structure tridimensionnelle du domaine CC2-LZ de NEMO obtenue à partir des coordonnées cristallographiques du cristal selon l'une des revendications 1 à 9.
20. Composé identifié selon une méthode selon l'une des revendications 18 ou 19, caractérisé en ce qu'il inhibe la dimérisation du domaine CC2-LZ de NEMO ou inhibe l'interaction du domaine CC2-LZ de NEMO avec les chaînes polyubiquitines.
PCT/FR2009/000127 2008-02-05 2009-02-05 Structure cristalline du domaine cc2-lz de nemo Ceased WO2009115664A2 (fr)

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EP09722579A EP2240513A2 (fr) 2008-02-05 2009-02-05 Structure cristalline du domaine cc2-lz de nemo
CA2713884A CA2713884A1 (fr) 2008-02-05 2009-02-05 Structure cristalline du domaine cc2-lz de nemo
JP2010545522A JP5529759B2 (ja) 2008-02-05 2009-02-05 Ｎｅｍｏのｃｃ２−ｌｚドメインの結晶構造
EA201001228A EA020189B1 (ru) 2008-02-05 2009-02-05 Кристаллическая структура сс2-lz домена nemo
AU2009227090A AU2009227090B2 (en) 2008-02-05 2009-02-05 Crystalline structure of the CC2-LZ domain of NEMO
US12/735,671 US8440790B2 (en) 2008-02-05 2009-02-05 Crystal structure of the CCZ-LZ domain of NEMO

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ATE476443T1 (de) * 2003-02-27 2010-08-15 Max Planck Gesellschaft Kristallstruktur des ternären komplexes aus 14-3- 3, fusicoccin und plasma-membran atpase und methoden zum design neuer herbizide
KR20060090714A (ko) * 2003-09-24 2006-08-14 앵스띠뛰 파스퇴르 Ｎｅｍｏ 올리고머화를 차단하기 위한 펩티드에 의한ｎｆ―ｋａｐｐａｂ 활성의 선택적 억제

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CA2713884A1 (fr) 2009-09-24
FR2927080A1 (fr) 2009-08-07
EP2240513A2 (fr) 2010-10-20
AU2009227090A1 (en) 2009-09-24
JP5529759B2 (ja) 2014-06-25
AR070555A1 (es) 2010-04-21
AU2009227090B2 (en) 2012-05-03
EA020189B1 (ru) 2014-09-30
JP2011516405A (ja) 2011-05-26

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