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TW200815028A - Conjugation process - Google Patents

Conjugation process Download PDF

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Publication number
TW200815028A
TW200815028A TW096111419A TW96111419A TW200815028A TW 200815028 A TW200815028 A TW 200815028A TW 096111419 A TW096111419 A TW 096111419A TW 96111419 A TW96111419 A TW 96111419A TW 200815028 A TW200815028 A TW 200815028A
Authority
TW
Taiwan
Prior art keywords
asn
ala
thr
lys
asp
Prior art date
Application number
TW096111419A
Other languages
English (en)
Other versions
TWI425951B (zh
Inventor
Ralph Leon Biemans
Pierre Duvivier
Tomas Maira-Litran
Original Assignee
Glaxosmithkline Biolog Sa
Brigham & Womens Hospital
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB0606416A external-priority patent/GB0606416D0/en
Priority claimed from GB0606417A external-priority patent/GB0606417D0/en
Application filed by Glaxosmithkline Biolog Sa, Brigham & Womens Hospital filed Critical Glaxosmithkline Biolog Sa
Publication of TW200815028A publication Critical patent/TW200815028A/zh
Application granted granted Critical
Publication of TWI425951B publication Critical patent/TWI425951B/zh

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/085Staphylococcus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6415Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/643Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/646Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55544Bacterial toxins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55555Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55572Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55577Saponins; Quil A; QS21; ISCOMS
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/60Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031Proteins
    • A61K2039/6037Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00Drug, bio-affecting and body treating compositions
    • Y10S424/831Drug, bio-affecting and body treating compositions involving capsular polysaccharide of bacterium, e.g. polyribosyl ribitol phosphate

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Toxicology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Peptides Or Proteins (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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200815028 九、發明說明: 【發明所屬之技術領域】 本發明係關於共軛領域且提供一種使PNAG與載體蛋白 共軛之方法。可進一步調配PNAG-載體蛋白共軛物以提供 疫苗。本發明亦包括PNAG-載體蛋白共軛物、包含pNAG_ ▲載體蛋白共軛物之疫苗及其在治療中之用途。 ^ 【先前技術】 近年來,社區獲得性及醫院獲得性感染數量隨著血管内 _ 裝置使用增加而增加。醫院獲得性(醫院)感染為發病率及 死亡率之主要因素,更尤其在美國,醫院獲得性感染每年 感染兩百萬以上患者。根據大量研究,約6%之美國患者 在其住院期間獲得感染。據估計,1992年美國之經濟負擔 超過 45億美元(Emori及 Gaynes,1993,Clin· Microbiol. Rev· 6; 428)。最常見感染為尿道感染(UTI佔感染之33%)、接著 為肺炎(15.5%)、手術部位感染(14.8%)及原發性血流感染 (13%)(Emori 及 Gaynes,1993, Clin. Microbiol. Rev. 6; Φ 428)。 金黃色葡萄球菌“Mrews)、凝固酶陰性葡 萄球菌(Coagulase-negative Staphylococci,主要為表皮葡 W . 萄球菌{Staphylococcus epidermidis))、腸球菌 spp)、大腸桿菌(五co//)及綠腹桿菌 aerwghosa)為主要醫院病原體。雖然彼等病 原體幾乎引起相同數量之感染,但其可產生之病症之嚴重 程度與耐抗生素性分離物之頻率平衡了對金黃色葡萄球菌 119629.doc 200815028 及表皮葡萄球菌之此等級,纟中金黃色葡萄球菌及表皮葡 萄球菌為最顯著醫院病原體。 金黃色葡萄球菌為具有顯著發病率及死亡率之醫院感染 的最常見原因(Romero-Vivas 等人 1995,infect. Dis 21. 1417)。其為骨髓炎、心内膜炎、膿毒性關節炎、肺炎、 膿腫及中毒性休克症候群之某些病例之起因。 表皮葡萄球菌為正常皮膚共生體,其亦為造成植入醫學 裝置感染及外科手術部位感染之原因的重要伺機性病原 體。經表皮葡萄球菌感染之醫學裝置包括心臟起搏器、腦 脊髓液分流器、持續性攜帶式腹膜透析導管、矯形術裝置 及人工心臟瓣膜。 用抗生素處理金黃色葡萄球菌及表皮葡萄球菌感染,其 中盤尼西林(penicillin)為供選擇藥物,而萬古黴素 (vancomycin)用於耐二甲氧苯青黴素分離物。自2〇世紀八 十年代以來,顯示廣泛耐抗生素性之葡萄球菌株之百分比 已曰漸盛行(Panlilo 等人 1992,lnfect· control· H〇Sp. Epidemiol. 13; 582),此對有效抗菌治療構成威脅。此 外,近來耐萬古黴素之金黃色葡萄球菌株之出現已引起耐 二甲氧苯青黴素之表皮葡萄球菌出現且蔓延之恐慌,因為 其無法得到有效治療。 已研究在陰性免疫療法中使用抗葡萄球菌抗原之抗體的 另一種方法。包括投與多株抗血清之療法處於發展中(WQ 00/15238、WO 00/12132),用抗脂磷壁酸之單株抗體處理 亦在發展中(WO 98/57994)。 119629.doc 200815028 另一種方法為使用活性疫苗接種以產生抗葡萄球菌之免 疫反應。已鑑別包括為疫苗組份之若干候選物。此等包括 聚N-乙醯化葡糖胺(PNAG),其為在葡萄球菌(例如金黃色 葡萄球菌及表皮葡萄球菌)中發現之表面多醣。此抗原尤 其在呈去乙醯化形式(dPNAG)之情況下已顯示其產生調理 ‘ 素免疫反應(WO 04/43405)。WO 04/43405揭示使用有機氰 . 化劑四氟硼酸1-氰基-4-二曱基胺基吡錠(CDAP)使PNAG與 載體蛋白共軛及藉由用戊二醛活化載體蛋白接著還原胺化 _ 來使dPNAG與載體蛋白共軛。 所述CDAP共軛不適於與dPNAG共同使用,因為經活化 之dPNAG可與dPNAG上之NH2基團反應使得若使用CDAP 化學處理則存在dPNAG交聯之風險。所述用於共軛dPNAG 之方法具有缺點,其使用戊二醛處理作為第一步以將醛基 引至載體蛋白上。因為戊二醛之不同分枝可導致不同結 果’所以戊二醛處理往往使得再生不可靠。戊二醛處理亦 可導致載體蛋白交聯。 需要避免使用戊二醛之使去乙醯化PNAG與載體蛋白共 輛之其他方法以最大程度使用PNAG作為疫苗組份。 . 【發明内容】 本發明之第一態樣提供一種使N_乙醯化少於40%之 PNAG與载體蛋白共輕之方法,該方法包·含以下步驟: a) 藉由添加包含順丁烯二醯亞胺基之鍵聯劑來活化 PNAG以形成活化之PNAG ; b) 藉由添加包含魏基之鍵聯劑來活化載體蛋白以形成活 119629.doc 200815028 化之載體蛋白;及 C)使活化之PNAG與活化之載體蛋白反應以形成PNAG-載體蛋白共軛物;或 a)藉由添加包含髄基之鍵聯劑來活化PNAG以形成活化 之PNAG ; • b)藉由添加包含順丁烯二醯亞胺基之鍵聯劑來活化載體 . 蛋白以形成活化之載體蛋白;及 c)使活化之PNAG與活化之載體蛋白反應以形成PNAG- • 載體蛋白共軛物;或 a) 藉由添加包含Μ基之鍵聯劑來活化PNAG以形成活化 之PNAG ; b) 藉由添加包含巯基之鍵聯劑來活化載體蛋白以形成活 化之載體蛋白;及 c) 使活化之PNAG與活化之載體蛋白反應以形成PNAG-載體蛋白共輊物。 本發明之第二態樣提供一種製造疫苗之方法,該方法包 • 含進行本發明之共軛方法且添加合併PNAG-載體蛋白共軛 物與醫藥學上可接受之賦形劑之另一步驟。 \ 本發明之第三態樣提供可藉由本發明之方法獲得之 PNAG-載體蛋白共軛物。 本發明之第四態樣提供PNAG-載體蛋白共軛物,其中 PNAG少於40% N-乙醯化且PNAG與載體蛋白藉由包含鍵 結硫原子之順丁烯二醯亞胺基或鍵結硫原子之硫原子的鍵 聯劑接合。 119629.doc 200815028 本發明之第五悲樣提供N-乙醯化少於40%之活化 PNAG,其中PNAG共價鍵結包含順丁烯二醯亞胺基之鍵聯 劑。 本發明之第六態樣提供包含可由本發明之方法獲得之 PNAG·載體蛋白共輛物之疫苗。 本發明之另一態樣提供用於治療或預防葡萄球菌疾病之 本發明之PNAG-載體蛋白共軛物。 本發明之另一態樣提供本發明之pnag—載體蛋白共軛物 之用途,其係用於製備供治療或預防葡萄球菌疾病之疫 苗。 本發明之另一態樣提供一種治療或預防葡萄球菌疾病之 方法,其包含將本發明之疫苗投與人類或動物患者之步 驟。 【實施方式】 本發明描述一種用於使N-乙醯化少於4 〇、3 5、3 0、20、 15、10或5%之PNAG與載體蛋白共輛之方法,該方法包含 以下步驟: a) 藉由添加包含順丁烯二醯亞胺基之鍵聯劑來活化ρΝΑ(} 以形成活化之PNAG ; b) 藉由添加包含疏基之鍵聯劑來活化載體蛋白以形成活化 載體蛋白;及 c) 使活化之PNAG與活化之載體蛋白反應以形成pnag-載 體蛋白共輛物。 作為本發明之獨立態樣,本發明描述一種用於使乙醯 119629.doc 200815028 化少於40、35、30、20、15、10或5%之PNAG與載體蛋白 共軛之方法,該方法包含以下步驟: a) 藉由添加包含順丁烯二醯亞胺基之鍵聯劑來活化載體蛋 白以形成活化之載體蛋白; b) 藉由添加包含巯基之鍵聯劑來活化PNAG以形成活化之 , PNAG ;及 . c)使活化之PNAG與活化之載體蛋白反應以形成PNAG-载 體蛋白共軛物。 _ 作為本發明之獨立態樣,本發明描述一種用於使N-乙醯 化少於40、35、30、20、15、10或5%之PNAG與載體蛋白 共軛之方法,該方法包含以下步驟: a) 藉由添加包含巯基之鍵聯劑來活化載體蛋白以形成活化 之載體蛋白; b) 藉由添加包含Μ基之鍵聯劑來活化PNAG以形成活化之 PNAG ;及 c) 使活化之PNAG與活化之載體蛋白反應以形成PNAG-載 ® 體蛋白共軛物。 術語 PNAG 包含 dPNAG及 PNAG。PNAG 少於 40、35、 30、25、20、15、10、5、2或 1% N-乙醯化使得 PNAG 主要 呈去乙醯形式。PNAG之去乙醯化抗原決定基可引起能介 導調理素殺死革蘭氏陽性細菌(Gram positive bacteria)(例 如金黃色葡萄球菌及/或表皮葡萄球菌)之抗體。在一實施 例中,PNAG未經0-丁二醯化或在少於25、20、15、10、 5、2、1或0.1 %之殘基上經0-丁二醯化。 I19629.doc -11- 200815028 PNAG可為不同大小,自超過400 kDa至75與400 kDa之 間、至10與75 kDa之間、至由最多30個重複單元構成之寡 醣變化。任何大小之PNAG多醣或募醣可用於本發明之方 法中,例如超過40、50、60、80、100或200 kDa或在40-400 kDa、50-350 kDa、40-300 kDa、60-300 kDa、50-250 kDa、60-200 kDa、70-150 kDa或 80-120 kDa之間。大小調 整可藉由此項技術中已知之任何方法、例如藉由微流化、 超音波照射或藉由化學分解(WO 03/53462、EP497524、 EP497525)來達成。 在一實施例中,藉由化學處理天然多醣使PNAG去乙醯 基化以形成dPNAG。例如,用鹼性溶液處理天然PNAG使 得pH值升至10以上。例如,用0.1-5 Μ、0.2-4 Μ、0.3-3 Μ、0·5-2 Μ、0.75-1.5 Μ、約 1.5 Μ、約 2 Μ、約 5 Μ或約 1 Μ 之 NaOH、ΚΟΗ 或 ΝΗ4ΟΗ 處理 PNAG。在 20-100、25-80、 3 0-60或3 0-50或3 5-45°C之溫度下處理歷時至少10或30分鐘 或 1、2、3、4、5、10、15、20 或 24小時。dPNAG可如 WO 04/43405中所述來製備。 共軛為PNAG與載體蛋白之共價偶合。其可為直接或間 接的,併入與活化PNAG及活化載體蛋白之順丁烯二醯亞 胺基及巯基反應之另一交聯化合物。 術語鍵聯劑係指在已完成之共軛物中共價連接PNAG與 載體蛋白之分子。鍵聯劑可源於用於共軛反應中之兩個分 子之共價鍵結。或者,鍵聯劑可來源於用於共軛反應(例 如在來自載體蛋白之半胱胺酸殘基之髄基與活化PNAG上 119629.doc -12- 200815028 之順丁稀二醯亞胺基或魏基反應之情況下)中之單個分 子。 在第一實施例之一態樣中,在步驟a)期間包含順丁嫦二 醯亞胺基之鍵聯劑連接PNAG上之胺基。 在第二實施例之一態樣中,在步驟b)期間包含順丁烯二 醯亞胺基之鍵聯劑連接載體蛋白上之胺基。
在一實施例中,鍵聯劑包含衍生自選自由BMPS、 EMCS、GMBS、MBS、LC-SMCC、SMCC、SMPB、 SMPH、磺基-EMCS、磺基-MBS、磺基-SMCC、確基-GMBS及石黃基-SMPB組成之群之化合物的順丁稀二酿亞胺 基。 在一實施例中,包含順丁烯二醯亞胺基之鍵聯劑具有5_ 10、6-8、10-20、12-17、約7、約10或約15埃之間隔長 度0 在一實施例中’在步驟a)期間,PNAG與包含順丁婦二 醢亞胺基之鍵聯劑的重量/重量比率為1:2〇_2〇:ι、 I··1、、1··5·5:1、1:2_2:1、1:1.5_15:1 或約 h 1:10。 、、、勺思謂數字應在所提供之數字之1 〇%内。 在-實施例中’藉由添加包含順丁浠二酿亞胺基 劑活化PNAG或載體蛋白的步驟在6.0-9.0、6.0_8.5、7 5_ 8’5、6·5-7·5 或約 7.〇?il8(^pH 值下進行。 … 在一實施例中,在步驟小叫期間, 連接載體蛋白上之脖其.^ μ基之鍵%劑 之^基。在一實施例中,在步驟b)期間, 119629.doc -13- 200815028 包含巯基之鍵聯劑連接pnag上之胺基。 在一實施例中,鍵聯劑包含衍生自或可衍生自選自由 SPDP、LC-SPDP、SMPT、LC-SMPT、磺基-SPDP、磺基-SMPT、磺基-LC-SMPT、磺基-LC-SPDP及N-乙醯基同型 半胱胺酸硫内酯組成之群之化合物的髓基。 在一實施例中,包含Μ基之鍵聯劑具有4-25、5-10、6-8、10-20、13-17、5-20、約7或約15埃之間隔長度。 在PNAG藉由添加第一鍵聯劑來活化且載體蛋白藉由添 加第二鍵聯劑來活化之實施例中,第一及第二鍵聯劑視情 況分別衍生自或可衍生自GMBS及SPDP、GMBS及LC· SPDP、磺基-GMBS 及 SPDP、磺基-GMBS 及 LC-SPDP、 SPDP及 GMBS、SPDP及磺基-GMBS ; LC-SPDP及 GMBS ; 或 LC-SPDP及磺基-GMBS。 在PNAG藉由添加包含巯基之第一鍵聯劑來活化且載體 蛋白藉由添加包含酼基之第二鍵聯劑來活化之實施例中, 第一及第二鍵聯劑可相同或不同。例如,第一及第二鍵聯 劑可分別衍生自或可衍生自SPDP及SPDP ; SPDP及LC-SPDP ; SPDP 及 SMPT ; SDPDILC-SMPT、LC-SPDP 及 SDPD、LC-SPDP 及 LC-SPDP ; LC-SPDP 及 SMPT、LC-SDPD 及 LC-SMPT ; SMPT 及 SPDP ; SMPT 及 LC-SPDP ; SMPT 及 SMPT ; SMPT 及 LC-SMPT ; LC-SMPT 及 SPDP ; LC-SMPT 及 LC-SDPD、LC-SMPT 及 SMPT 或 LC-SMPT 及 LC-SMPT 〇 在一實施例中,在藉由添加包含巯基之鍵聯劑來活化載 119629.doc -14- 200815028 騎基之鍵聯劑與載體蛋白之重量/ 體蛋白之步驟期間,包含 重量比率為100:14 10:1 ' 50:1.2:1 > 50:1 ·100、1:1-1:100、100:1-1:1、1〇〇:1_ -20* 1 、20:1-3:1、15:1-5:1 或約 1〇:1 在一實施例中,藉由沃丄 疋人 *力17包含魏基之鍵聯劑來活化載體 蛋白之步驟在6.0-9.〇、7nQn /.0-9.0、7·5-8·5 或約 8.0之 pH值下 進行。 在一實施例中,在舟職、 乂驟勾期間,活化PNAG與活化載體 蛋白之重量/重量比率為 午马1〇:1-1:1〇、9:1-1:5、8:1_1:2、7:1- 1:1、5:1 -1:1 或約 2: j。 在貝知例中,步驟〇在6 〇 9 〇、6 〇一8 〇、6 5_7 $或約 7·〇之pH值下進行。 在實施例中’步驟c)完成後PNAG與載體蛋白之間的 鍵聯劑長度為 5-40、ίο,、12-25、1(M5、15_25、2〇_ 25、20-30、25-30、30-40、約 14、約 23、約 28或約 30埃。 在貝施例中,本發明之方法包含用半胱胺酸阻斷過量 順丁烯二醯亞胺基之另一步驟d)。 在一實施例中,載體蛋白係選自由下列各物組成之群: 破傷風類毒素、白喉類毒素、CRM197、rEPA、蛋白D、 SitC/MntC/唾液結合蛋白、EbhA、EbhB、彈性蛋白結合蛋 白(EbpS)、EFB(FIB)、SBI、ClfA、SdrC、SdrG、SdrH、 脂肪酶 GehD、SasA、FnbA、FnbB、Cna、ClfB、FbpA、 Npase、IsaA/PisA、SsaA、EPB、SSP-1、SSP-2、HBP、 玻璃連接蛋白、金纖維蛋白原結合蛋白、凝固酶、Fig、 MAP、IsdA、IsdB、HarA、SitC、α毒素(Hla)、α毒素 119629.doc -15- 200815028 H35R突變體、MRPII及自溶素或其片段。 目前用於偶合多醣或寡醣免疫原之載體蛋白之實例包括 白喉及破傷風類毒素(DT、DT CRM197及TT)、透孔螺如 藍蛋白(KLH)、綠膿桿菌外蛋白α(γΕΡΑ)及經純化之結核菌 素蛋白衍生物(PPD)、自流行性感冒嗜血桿菌丨丑此所叩以/似 ~/^e^zzae)之蛋白D、肺炎球菌溶血素或以上之任一者之 片段。適用片段包括包含T輔助抗原決定基之片段。詳言 之,蛋白D片段較佳含有蛋白之N末端1/3。蛋白D為自流 行性感冒嗜血桿菌之IgD結合蛋白(EP 〇 594 61〇 。 用於本發明之方法中之另—載體蛋白為單個葡萄球菌蛋 白或其片段或包含至少或確切丨、2、3或4個或4個以上葡 萄球菌蛋白(例如選自以下所揭示之彼等或其片段)之融合 蛋白。 在一實施例中,a毒素用作載體蛋白。因為共軛方法大 大減少或移除毒性,所以可使天·然形式來與多醣共輕。因 為殘餘毒性較低,所以經遺傳去毒之a毒素(諸如出狐⑽ 或His 35 Arg變異體)較佳用作載體。或者藉由用交聯劑甲 搭或戊二搭處理來化學上將《毒素去毒。經遺傳去毒之《毒 素視情況較佳藉由用交聯劑甲醛或戊二醛處理 毒以進一步減少毒性。 子 在一實施例中’本發明之方法包含合併PNag_載體蛋白 共軛物與視情況包含佐劑之醫荜學 呆予上了接文之賦形劑的另 一步驟。 雖然適合佐劑包括I呂鶊,按‘ g备 堵如虱乳化銘凝膠(釁)或磷酸 119629.doc -16 - 200815028 鋁,但亦可為鈣鹽、鎂鹽、鐵鹽或鋅鹽,或可為醯化酪胺 酸或醯化糖、陽離子或陰離子衍生之多醣或聚磷腈之不溶 懸浮液。 在一實施例中,佐劑為TH1或TH2型反應之較佳誘導 劑。高含量之Thl型細胞因子傾向於促進細胞介導之對特 定抗原之免疫反應的誘發,而高含量之Th2型細胞因子傾 向於促進對該抗原之體液免疫反應之誘發。 重要的是記得Thl與Th2型免疫反應之區別並非絕對。事 實上,個體忍受描述為主要Thl或主要Th2之免疫反應。然 而,根據藉由 Mosmann 及 Coffman(Mosmann,T.R.及 Coffman, R.L. (1989) ΤΉ1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology, 7,第 145-173 頁)在鼠科動物CD4 +ve T細胞純系中所述,常便於考慮細 胞因子總科。傳統上,Thl型反應與藉由T-淋巴細胞產生 INF-γ及IL-2細胞因子相關。常與Thl型免疫反應之誘發直 接相關的其他細胞因子未由T細胞產生,諸如IL-12。相比 之下’ Th2型反應與11-4、IL-5、IL_6、IL-10之分泌相關。 促進主要Thl反應之適合佐劑系統包括:單磷醯脂A或其 衍生物,尤其3-去-0-醯化單磷醯脂A(3D-MPL)(其製備參 見GB 2220211 A);及單磷醯脂A(較佳3-去-0-醯化單磷醯 脂A)與鋁鹽(例如磷酸鋁或氫氧化鋁)或水包油乳液之組 合。在該等組合中,抗原及3D-MPL含於相同微粒結構 中,使得抗原及免疫刺激信號更有效傳遞。研究表明3D- 119629.doc -17- 200815028 MPL能進一步增強吸附礬之抗原的免疫原性[Thoelen等 人.Vaccine (1998) 16:708-14; EP 689454_B1]。 增強系統包括單磷醯脂A與皂素衍生物之組合,尤其如
WO 94/00153中所揭示之qS21與3D-MPL之組合,或如WO 96/33739中所揭示用膽固醇中止qS21之較少反應原性組合 物。包括QS21、3D-MPL及生育酚於水包油之乳液中之尤 其有效佐劑調配物描述於W〇 95/17210中。視情況而言, 疫苗額外包含皂素,更佳qS21。調配物亦可包含水包油乳
液及生育酚(WO 95/17210)。本發明亦提供一種製造疫苗 调配物之方法,該方法包含將本發明之pNAG共軛物與醫 藥學上可接受之賦形劑(諸如3D-MPL)—起混合。含有寡核 苷酉夂之未甲基化之CpG (w〇 96/〇2555)亦為thi反應之較 佳誘發劑且適用於本發明。佐劑視情況形成脂質體結構或 ISCOM結構。 QS21 :固醇之重量比通常為約1:1〇〇至1:1。在一實施例 中,存在過量固醇,QS21:固醇之重量比為至少Μ。對 人類投藥而言,QS21及固醇通常以每次給藥約工吨至約 l〇〇pg或約10μ§至約5〇吨之範圍存在於疫苗中。 :旨:體視情況含有中性脂質’例如磷脂酿膽鹼(視情況 在室溫下為非結晶體)’例如蛋黃翻醢膽驗、二油酿鱗 脂醯膽驗或雙月桂絲磷脂膽驗。脂質體亦可含有帶電 月曰=—〜加月曰質體由餘和脂質構成之脂質體-QS21結構 的系‘疋性。在此蓉姑俄 寺狀况下、電脂質之量視情況為1-20重 量% ’視情況為5·10重量%1醇與磷脂之比率為旧 119629.doc -18- 200815028 (mol/mol),視情況為 20-25%。 在一實施例中,佐劑含有MPL (3-去醯基之單磷醯脂A, 亦稱為 3D-MPL)。自 GB 2 220 211 (Ribi)已知 3D-MPL 為具 有4、5或6醯化鏈之3種類型去_0_醯化單磷醯脂A之混合物 且其藉由 Ribi Immunochem,Montana 製造(WO 92/ 116556) 〇 在一實施例中,佐劑含有最初在無MPL下製備之脂質 體,接著將MPL視情況以100 nm微粒添加至脂質體中。因 此,MPL不含在微脂粒膜内(稱為MPL在外.)。MPL含在微 脂粒膜内(稱為MPL在内)之組合物亦形成本發明之態樣。 抗原可含在微脂粒膜内或含在微脂粒膜外。視情況可溶抗 原在外且疏水性或脂抗原含在膜内或膜外。 在一實施例中,本發明之方法包含合併PNAG-載體蛋白 共軛物與額外抗原之另一步驟。在一實施例中,添加1、 2、3、4、5、6、7、8、9或10個額外抗原。在一實施例 中,額外抗原包含細菌多醣或寡醣。 該等抗原之實例包括來自5型及/或8型金黃色葡萄球菌 之莢膜多醣或募醣。 在人體中引起感染之大部分金黃色葡萄球菌株含有5型 或8型多醣。約60%人類菌株為8型的且約30%為5型的。5 型及8型莢膜多醣抗原之結構描述於Moreau等人 Carbohydrate Res· 201; 285 (1990)及 Fournier 等人 Infect· Immun· 45; 87 (1984)中。兩者在其重複單元中均具有 FucNAcp以及可用以弓j入魏基之ManNAcA 〇 119629.doc -19- 200815028 近來(Jones Carbohydrate Research 340, 1097-1106 (2005)) NMR光譜分析修改了此等莢膜多醣之結構: 5型 —4)_P-E|-ManNAcA-(l—4)-a-L-FucNAc(30Ac)-(l —3)-β_ D-FucNAc-( 1 —> • 8型 - ->3)-P-D-ManNAcA(40Ac)-(l-^3)-a-L-FucNAc(l-^3)-a- D-FucNAc(l —> _ 使用熟練技術者熟知之方法可自合適金黃色葡萄球菌株 萃取多醣,例如US 6294177中所述。舉例而言,ATCC 12902為5型金黃色葡萄球菌株,且ATCC 12605為8型金黃 色葡萄球菌株。 多醣可為天然大小或可例如藉由微流化、超音波照射或 藉由化學處理來調整大小。寡醣亦可用於本發明之方法 中〇
視情況使本發明之方法中所用之5型及8型多醣與可為以 ® 上所述之彼等載體蛋白的任何載體蛋白共輛(例如使用US 4372945、US 4474757、US 4356170、US 4830852 或 WO . 95/08348之任一者中所揭示之方法)或其可為未經共軛的。 在一實施例中,額外抗原包含自US 6294177&Fattom& Guidry Am. J. Vet. Res. 60: 530 (1999)中所述之金黃色葡 萄球菌之336抗原。 在一實施例中,336抗原為天然大小或可例如藉由微流 化、超音波照射或藉由化學處理調整大小之多醣。亦可使 119629.doc •20- 200815028 〜用來源於336抗原之寡醣。使用任何已知之共軛方法(例如 US 4372945 - US 4474757 > US 4356170 - US 4830852 或 WO 95/08348中所述之彼等方法)使336抗原較佳與載體蛋 白共輛或其可為未經共辄的。 表皮葡萄球菌之菌株ATCC-31432、SE-360及SE-10特徵 • 在於三種不同莢膜類型,分別為I、II及III型(Ichiman及 . Yoshida 1981,J· Appl· Bacteriol. 51; 229)。萃取自表皮葡
萄球菌之每一血·清型之莢膜多醣構成I型、II型及III型多 _ 醣。多醣可藉由若干方法來萃取,該等方法包括US 4197290 中所述或如 Ichiman 等人 1991,J· Appl· Bacteriol· 71; 176中所述之方法。
在本發明之一實施例中,額外抗原包含自表皮葡萄球菌 之I型及/或II型及/或III型多醣或寡醣。多醣可為天然大小 或可(例如)籍由微流化、超音波照射或化學分解調整大 小。額外抗原亦可包括自表皮葡萄球菌株萃取之寡醣。此 等多醣或寡醣未經共軛或較佳使用任何已知之共軛方法 _ (例如 US 4372945、US 4474757、US 4356170、US 4830852或WO 95/08348中所述之方法)共軛。 ' 在一實施例中,額外抗原包含葡萄球菌蛋白或其片段。 • 例如自金黃色葡萄球菌或表皮葡萄球菌之蛋白。本發明之 某些實施例含有自金黃色葡萄球菌及表皮葡萄球菌之蛋 白。舉例而言,額外抗原為分離蛋白,其包含至少85%、 較佳至少90°/。、更佳至少95%、最佳至少97-99%或準確與 序列表中任一序列之胺基酸序列相同的胺基酸序列。 119629.doc -21- 200815028 田蛋白在本文中特別提及之情況下,可提及天然或重組 之全長蛋白或視情況任何信號序列已被移除之成熟蛋白。 蛋白可直接自葡萄球菌株分離或藉由重組DNA技術產生。 蛋白之免疫原性片段可併入本發明之免疫原性組合物。此 等片段為包含連續取自蛋白之胺基酸序列之至少〗〇個胺基 酸、至少20個胺基酸、至少3〇個胺基酸、至少4〇個胺基 酸、至少50個胺基酸或至少1〇〇個胺基酸之片段。此外, 該等免疫原性片段通常與抵抗葡萄球菌蛋白而產生之抗體 或與藉由經葡萄球菌感染之哺乳動物宿主所產生之抗體免 疫反應或含有T細胞抗原決定基。免疫原性片段亦包括當 以有效劑量投與時(單獨或作為結合載體之半抗原)引起2 抗葡萄球菌感染之保護免疫反應(視情況抵抗金黃色葡萄 球菌及/或表皮葡萄球菌感染)之片段。該免疫原性片段可 包括(例如)缺乏N末端前導序列及/或跨膜域及/或〇末端錨 定域之蛋白。在-實施例中,本發明之方法中所用之免疫 原性片段實質上包含蛋白之所有胞外域 其與選自序列表
片段。或者本發明亦包括葡萄球菌蛋白或其片 同蛋白内之 段之個別融 119629.doc •22- 200815028 合蛋白作為具有異種序列之融合蛋白,諸如τ細胞抗原決 定基或純化標籤之供應者,例如β-半乳糖甘酶、麩胱甘肽-S-轉移酶、綠色螢光蛋白(GFP) '抗原決定基標籤(諸如 FLAG、myc標籤、聚組胺酸或諸如流感病毒紅血球凝集素 之病毒表面蛋白)或細菌蛋白(諸如破傷風類毒素、白喉類 - 毒素、CRM197)。 , 額外抗原視情況包含葡萄球菌胞外組份結合蛋白或葡萄 球菌轉運體蛋白或葡萄球菌毒素或毒性調節劑。額外抗原 _ 視情況包含至少或確切1、2、3、4、5或6種葡萄球菌蛋 白。胞外組份結合蛋白之實例為昆布胺酸(laminin)受體、 SitC/MntC/唾液結合蛋白、EbhA、EbhB、彈性蛋白結合蛋 白(EbpS)、EFB(FIB)、SBI、自溶素、ClfA、SdrC、 SdrG、SdrH、脂肪酶 GehD、SasA、FnbA、FnbB、Cna、 ClfB、FbpA、Npase、IsaA/PisA、SsaA、EPB、SSP-1、 SSP_2、HBP、玻璃連結蛋白、血纖維蛋白原結合蛋白、 凝固酶、:Fig及MAP。葡萄球菌轉運體蛋白之實例為免疫 ® 優勢ABC轉運體、IsdA、IsdB、Mg2+轉運體、SitC及
Ni ABC轉運體。葡萄球菌毒素或毒性調控劑之實例為α ’ 毒素(Hla)、α毒素H35R突變體及RNA III活化蛋白 . (RAP)。 * 本發明之另一態樣為藉由本發明之方法可獲得或所獲得 之PNAG-載體蛋白共軛物。 本發明之PNAG-載體蛋白共軛物包含N-乙醯化少於40% 之PNAG,且PNAG與載體蛋白藉由包含鍵結硫原子之順丁 119629.doc -23- 200815028 烯二醯亞胺基之鍵聯劑接合。 在一實施例中,順丁烯二‘亞胺基位於PNAG與硫原子 之間。或者順丁婦二醯亞胺基位於載體蛋白與硫原子之 間。 在一實施例中,PNAG-載體蛋白共軛物具有結構:
其中R1及R2獨立選自視情況經取代之芳族鏈或脂肪鏈或 一鍵。在一實施例中,R1為C1-C6烷基、C2-C5烷基、C3-C4烷基、C2烷基、C3烷基、C4烷基或C5烷基。在一實施 例中,R2為C1-C6烷基、C2-C5烷基、C3-C4烷基、C2烷 基、C3烷基、C4烷基或C5烷基。
在一實施例中,本發明之PNAG-载體蛋白共軛物具有結 構·· 載體蛋白
PNAG 其中R1及R2獨立選自視情況經取代之芳族鏈或脂肪鏈或 一鍵。在一實施例中,R1為C1-C6烷基、C2-C5烷基、C3- 119629.doc -24- 200815028 C4烷基、C2烷基、C3烷基、C4烷基或C5烷基。在一實施 例中,R2為C1-C6烷基、C2-C5烷基、C3-C4烷基、C2烷 基、C3烷基、C4烷基或C5烷基。 本發明之另一態樣為PNAG-載體蛋白共軛物,其中 PNAG少於40% N-乙醯化,且PNAG與載體蛋白藉由包含 鍵結硫原子之硫原子之鍵聯劑接合。 在一實施例中,PNAG-載體蛋白共軛物具有結構:
PNAG、
N 、載體蛋白
其中R1及R2獨立選自視情況經取代之芳族鏈或脂肪鏈或 一鍵。在一實施例中,R1為C1-C6烷基、C2-C5烷基、C3-C4烷基、C2烷基、C3烷基、C4烷基或C5烷基。在一實施 例中,R2為C1-C6烷基、C2-C5烷基、C3-C4烷基、C2烷 基、C3烷基、C4烷基或C5烷基。 在一實施例中,PNAG-載體蛋白共軛物具有結構:
本發明之另一態樣為N-乙醯化少於40%之活化PNAG, 其中PNAG共價鍵結包含順丁烯二醯亞胺基之鍵聯劑。在 一實施例中,順丁烯二醯亞胺基鍵聯劑包含衍生自或可衍 119629.doc -25- 200815028 生自選自由 BMPS、EMCS、GMBS、MBS、LC-SMCC、 SMCC、SMPB、SMPH、磺基-EMCS、磺基-MBS、磺基-SMCC、磺基-GMBS及磺基-SMPB組成之群之化合物。 在一實施例中,活化PNAG具有結構:
其中R1係選自視情況經取代之芳族鏈或脂肪鏈或一鍵。在 一實施例中,R1為C1-C6烷基、C2-C5烷基、C3-C4烷基、 C2烷基、C3烧基、C4烷基或C5烷基。在一實施例中,鍵 聯劑長5-4〇、1〇-30、12-25、10-15、15-25、20-25、20-30、25-30、30-40、約 14、約 23、約 28 或約 30埃。 藉由本發明之方法製成之PNAG-載體蛋白共軛物及疫苗 製劑可藉助於經由全身途徑或黏膜途徑投與該疫苗用以保 護或治療易受感染之哺乳動物。此等投藥可包括經由肌肉 内、腹膜内、皮内或皮下途徑注射;或經由黏膜投與口腔/ 食道、啤吸道、泌尿生殖道。雖然本發明之疫苗可以單一 劑量投與,但其組份亦可在相同時間或不同時間共投藥。 對共投藥而言,可選Thl佐劑可存在於任何或所有不同 投藥中,然而若其與疫苗之細菌蛋白組份組合存在則較 佳。除單一投藥途徑外,可使用兩種不同投藥途徑。例 如,多醣可經肌肉内(或皮内)投與且細菌蛋白可鼻内(或皮 内)投與。此外,對預致敏劑量而言本發明之疫苗可肌肉 119629.doc -26- 200815028 内投與’且對加強劑量而言可鼻内投與。 選擇各疫苗中共輛抗原之量為誘發無典型疫苗中顯著、 不利副作用之免疫保護反應之量。該量視使用何種特定免 疫原及其如何呈現而變。一般而言,預期各劑量包含〇 100 多釀,較佳〇 ^50吨多醣共輛物,較佳〇 11〇叩, 更佳1-10 ,其中1至5吨為更佳範圍。 疫田中蛋白抗原含量通常在1-1〇〇 pg、較佳5_5〇叩之範 圍内敢通韦在5-25 pg之範圍内。在最初疫苗接種後,受 檢者可接收一或若干次充分間隔之加強免疫。 疫田製備一般描述於Vaccine Design ("The subunit and adjuvant approach”(Powell M.F· & Newman 1VLJ·編)(1995) Plenum Press New York)中。用脂質體封裝係描述於 Fullerton之美國專利第4,235,877號。 本發明之疫苗可儲存於溶液中或經凍乾。溶液較佳在糖 (諸如蔗糖、海藻糖或乳糖)存在下凍乾。疫苗經凍乾且在 使用前臨時再生仍更佳。凍乾可導致吏穩定組合物(疫苗) 且在3D-MPL存在下及以鋁為主之佐劑缺乏下可能導致更 高抗體力價。 在各情況下本發明者期望本文之術語”包含"視情況可用 術語’’由·.·組成”代替。 本專利說明書内所引用之所有文獻或專利申請案均以引 用的方式併入本文中。 為更好地理解本發明而提出以下實例。此等實例僅為達 成說明之目的,且不應解釋為以任何方式限制本發明之範 119629.doc -27- 200815028 實例 實例1 PNAG-TT共軛物之製備 dPNAG如WO 04/43405中所述來製備。在Super〇se 6管 柱上進一步純化dPNAG。 dPNAG活化 . 將 dpNAG(12 mg)溶於 300 μΐ 5 M HC1+300 μΐ 5 μ
NaOH+1700 μΐ lxPBS (pH值7·0)中,且將_值調節至 # 7·0。經由0·22 μηι過濾器過濾樣品且將ρΗ值再次調節至 7.0。將12 mg GMBS添加於200 μΐ DMSO中,且在室溫下 在黑暗中緩慢攪拌樣品2小時。用0·5 M NaOH將ΡΗ值保持 在7.0。使用經lxPBS、10 mM EDTA (pH值7.0)緩衝液平衡 之脫鹽管柱(PD10管柱)移除過量GMBS,且使用Centricon 10 KDa MWCO濃縮裝置濃縮樣品。 TT活化 將破傷風類毒素(ΤΤ)(6·5 mg; 195 μΐ儲備溶液)添加至 _ 1105 μΐ含有 10 mM EDTA之 lxPBS (pH值 8.0)中。將 13〇 SPDP (DMSO中6.2 mg/ml)添加至蛋白溶液中,且在室溫下 > 在黑暗中缓慢攪拌樣品1小時。使用〇·5 Μ NaOH將pH值保 ^ 持在8·0。使用經lxPBS、10 mM EDTA (pH值8·〇)緩衝液平 < 衡之脫鹽管柱(PD10管柱)移除過量SPDP,且使用
Centricon 10 KDa MWCO 濃縮樣品至 1.3 ml。將 〇 65 DTT (lxPBS、10 mM EDTA (pH 值 8·0)緩衝液中 23 mg/ml) 添加至1·3 ml經SPDP活化之TT中。將樣品在室溫下黑暗+ 119629.doc -28- 200815028 培育30分鐘。使用〇·5 M NaOH將pH值保持在8·0。使用經 IxPBS、1〇 mM EDTA (pH值7.0)緩衝液平衡之脫鹽管柱 (PD10管柱)移除過量dtt,且使用Centricon 10 KDa MWCO濃縮裝置濃縮樣品至〇.6 ml。 將經 GMBS活化之Dpnag (0.6 ml)+SH-SPDP-TT (0·6 ml) 混合且在室溫下黑暗中緩慢攪拌2小時。在1〇() μ1 lxPBS、1〇 mM EDTA (pH值7.0)中用3 mg半胱胺酸阻斷過 量順丁烯二醯亞胺,歷時30分鐘。在以lxPBS、10 mM EDTA (pH值7.0)作為電泳緩衝液之1 mi/min之sUper〇se 6管 柱上層析樣品。使用Bradford檢定測試溶離份之蛋白。將 含有共輛物之溶離份彙集且使用Spectra/gel吸附劑濃縮至 25 ml。測試最終共軛物之多醣及蛋白組成。 dPNAG-TT組合物 dPNAG : 153.37 μβ/ηι1(46.3%) ΤΤ : 178.06 Mg/mi(53.7%) 實例2 dPNAG之活化及偶合 dPNAG-ΤΤ共軛物
使用下文所述之方法產生以下共軛物: dPNAG-ΤΤΟΙΟ : dPNAG_S_GMBS+經 DTT 處理之 TT-LC-SPDP
dPNAG-TTOll ·· dPNAG-S-GMBS+經 DTT 處理之 TT-LC· SPDP
dPNAG-TT012 : dPNAG-S-GMBS +經DTT處理之TT-SPDP 119629.doc -29- 200815028
dPNAG-TT014 : dPNAG-SPDP+經DTT處理之TT-SPDP dPNAG-TT017 :經 DTT處理之 dPNAG-SPDP+TT-LC-SPDP dPNAG-TT019 : dPNAG-S-GMBS+經DTT處理之TT-SPDP dPNAG-TT020 : dPNAG-S-GMBS+經DTT處理之TT-SPDP dPNAG - 將1 g PNAG以20 mg/ml之濃度溶於5 N HC1中,且培育1 , 小時。接著用5 N NaOH中和。在5 μπι膜上淨化溶液且在
Sephacryl S400HR上純化。彙集對應於”介質分子大小” _ (參見 Infection and Immunity,70: 4433-4440 (2002))之相關 溶離份且在去N-乙醯化處理前濃縮。 將溶液在1 M NaOH下調節且在37°C下放置24小時。中 和後,使產物經受透析及濃縮。 dPNAG活化
將S-GMBS(N-(y-順丁烯二醯亞胺基丁醯氧基)磺基丁二 酿亞胺,Pierce)添加至〇·2 M NaCl中之dPNAG (S-GMBS/PS (w/w)比率:1:1)中且在室溫下於pH值7.0(使用1 • M NaOH調節pH值)下培育2 h。藉由在使用PBS、10 mM
EDTA、50 mM NaCl (pH值7·2)作為溶離緩衝液而流動速率 ’ 固定在60 ml/h之Toyopearl HW-40F純化來移除過量GMBS , 及副產物。根據光學密度(UV=206 nm)選擇溶離池且接著 在 Vivaspin管 3000 MWCO或 Amicon Ultra 10,〇〇〇 MWCO上 濃縮。 偶合 混合經GMBS活化之dPNAG及經DTT還原之ΤΤ-SPDP且 119629.doc -30- 200815028 在室溫下攪拌。根據所用條件,在20-120 min後藉由添加 半胱胺酸(在pH值8.0之磷酸鈉緩衝液中4 mg/ml)來中止反 應,歷時30分鐘。在5 μπι過濾、器上淨化共輛物且注射於 Sephacryl S300HR樹脂(ΧΚ16/100)上以供純化。在流動速 率固定於30 ml/h之200 mM NaCl中實現溶離。藉由己_胺 ; 及藉由蛋白劑量來分析溶離份。將相關溶離份彙集且在 . 〇·22 μιη Sterivex上過濾。測試最終共軛物之多醣(己醣胺 劑量)及蛋白組合物(Lowry劑量)。 共軛物 N-乙醯化 程度% [dPNAG] mg/ml [TT] mg/ml PS範圍 (mg) 偶合時間 (min) dPNAG-TT 010 10* 15 15 30 120 dPNAG-TT Oil 10* 12 24 20 120 dPNAG-TT 012 10* 17.5 35 22 80 dPNAG-TT 019 34 5 10 10 20 dPNAG-TT 020 34 2 2 10 20 *在共軛中所用之部分上未進行但在先前部分上藉由NMr ⑩ __ 使用相同去-N-乙醯化方法評估。 共輛物 In.TT/PS 比率(w/w) F.TT/PS 比率(w/w) 產率 PS rec (%) 過濾 產率(%) dPNAG-ΤΤΟΙΟ 1/1 L86/1 43 99 dPNAG-TTOll 2/1 2.86/1 56 99 dPNAG-TT012 2/1 2.29/1 61 108~ dPNAG-TT019 2/1 1.45/1 81 97 dPNAG-TT020 1/1 0.89/1 82 109 dPNAG-SPDP : 將溶於DMSO(二甲亞砜,Merck)中之5倍莫耳過量之 SPDP (N- 丁 -—酿亞胺基-3 -(2· ^比唆基二硫基)丙酸酿,μw · 312.4,Pierce)添加至 100 mg以 5 mg/ml於 100 mM磷酸納(ρΗ 119629.doc -31 - 200815028 值 7·2)中之 dPNAG中。在 SephacrylS100HR(XK16/40)上純 化前,在Amicon Ultra 10,000 MWCO (以 3000 rpm 離心 28 min)上將反應混合物濃縮至土 6 ml。在流動速率固定在60 ml/h之pH值7.4之磷酸鹽緩衝液中實現溶離。彙集相關溶 離份(在 206 nm下讀出)且在 Amicon Ultra 10,000 MWCO(以 3000 rpm離心30分鐘)上濃縮至1.1 ml。 TT-SPDP : 將溶於DMSO(二曱亞砜,Merck)中之15倍莫耳過量之 SPDP(Pierce)添加至1 g於100 mM磷酸鈉(pH值7·2)中之TT (50 mg/ml)中,且在室溫下培育80 min。接著將產物注射 至Sephacryl S100HR (XK16/40)上且在流動速率固定在60 ml/h之 100 mM 乙酸鈉(pH值 5.6)、100 mM NaCl、1 mM EDTA中溶離。根據光學密度(UV=280 nm)選擇溶離池且接 著在 Amicon Ultra 10,000 MWCO (以 3000 rpm離心 75 min) 濃縮至19.6 ml。 TT-LC-SPDP產生為 TT-SPDP但使用 LC-SPDP(丁 二醯亞 胺基6·[3-(2-ϋ比咬基二硫基)-丙醯胺基]己酸醋,Pierce)及 60 min培育時間。
TT_SH 或 TT-LC-SH 將 DTT 添加至 TT-SPDP 或 TT-LC-SPDP 中,DTT/TT 比率 (mg/mg)為〇·7/1。室溫下2 h後,釋放吡啶-2·硫酮接著為其 在343 nm下之特徵吸收。藉由凝膠過濾、(PD-10,Amersham) 自過量DTT純化經硫醇化之蛋白。在Amicon Ultra 10,000 MWCO上濃縮後,藉由Lowry劑量評估蛋白含量。 119629.doc -32- 200815028 dPNAG-SPDP+TT_SH或 TT-LC-SH (dPNAG-TT0l4及 016) 在室溫下在連續攪拌下且在最初TT/PS比率(w/w)為2/1 下實施偶合。 將dPNAG與TT-SH混合以獲得20 mg/ml之最終PS濃度及 40 mg/ml之最終蛋白濃度。30 min後,藉由添加2-破代乙 酸胺(Merck)來中止未經反應之魏基。 將dPNAG與TT-LC-SH混合以獲得10 mg/ml之最終ps濃 度及20 mg/ml之最終蛋白濃度。75 min後,藉由添加2-破 代乙醯胺(Merck)來中止未經反應之酼基。 接著使用5 μπι Minisart過濾器淨化共軛物且將共軛物注 射於Sephacryl S300HR (XK16/100)上。在流動速率固定於 30 rnl/h之200 mM NaCl中實現溶離。 藉由己醣胺及藉由蛋白劑量來分析溶離份。將相關溶離 份囊集且在〇·22 μιη Sterivex上過滤。 所得共輛物具有2.18 (TT-SH)及2.24 (TT-LC-SH)之最終 TT/PS 比率(w/w) 〇 dPNAG硫醇化 將 11.6 mg DTT(1,4-二硫蘇糠醇,Boerhinger Mannheim, MW : 154·24)添加至 16.5 mg dPNAG-SPDP中。在室溫下 2 h後,釋放吡啶-2-硫酮接著為其在343 rim下之特徵吸收。 藉由凝膠過濾(Toyopearl HW40F)自過量DTT純化經硫醇化 之PS且接著在Amicon Ultra 10,000 MWCO上濃縮至860 μΐ 0 dPNAG-SH+TT-SPDP(dPNAG-TT017) 119629.doc -33- 200815028 在室溫下在連續攪拌下且在最初ΤΤ/PS比率(w/w)4 t 下實施偶合。 將dPNAG與TT-SPDP混合以獲得7.73 mg/ml之最終Ps c曲 度及13·3 mg/ml之最終蛋白濃度。90 min後,藉由添加之 峨代乙酸胺(Merck)來中止未經反應之魏基。 ' 接著使用5 μπι Minisart過濾、器淨化共轆物且將共輛物、、主 . 射於Sephacryl S300HR(XK16/100)上。在流動速率固定於 30 ml/h之200 mM NaCl中實現溶離。 # 藉由己醣胺及藉由蛋白劑量來分析溶離份。將相關溶離 份彙集且在0.22 μπι Sterivex上過濾。 所得共輛物具有2.74之最終丁17?8比率(\¥~)。 實例3 金黃色葡萄球菌dPNAG-TT共輛物之免疫原性 以0·3 pg之醣劑量為30隻小鼠之組皮下預防注射無佐劑 或與3D-MPL佐劑合併之金黃色葡萄球菌dPNAG_TT共軛 物。在第0、14及28天,小鼠接收三種預防注射。在第41 _ 天,自小鼠收集血清,且藉由ELISA測試各血清樣品以分 析抗PNAG之免疫反應。10隻小鼠之群用於對照組中且為 • 此等小,鼠預防注射生理食鹽水。 抗PNAG之ELISA ·· 將與稀釋於磷酸鹽緩衝生理食鹽水(PBS)中之甲基化 HSA (2_5 pg/ml)混合之經純化PNAG (2.5 pg/ml)在高結合 微量滴定盤(Nunc Maxisorp)上於4°C下塗佈隔夜。 室溫下,在攪動下將培養盤用1%之PBS_BSA阻斷30 119629.doc -34- 200815028 min。將小鼠抗血清預先稀釋1/100,接著進一步在微定量 盤中進行兩倍稀釋且在37°C下培育1小時。洗滌後,使用 Jackson ImnumoLaboratories Inc之在 PBS-BSA 0.2%-tween 0.05%中稀釋1:5000倍之過氧化酶共輒之affinipure山羊抗 小鼠IgG (H+L)(ref: 115_03 5-0Ό3)來偵測結合鼠科動物抗 體。在室溫下在攪動下培育偵測抗體歷時30 min。在室溫 下在黑暗中使用每10 ml pH值4 · 5 0 · 1Μ檸樣酸鹽緩衝液4 mg OPD (Sigma)+5 μΐ Η202歷時15分鐘形成顏色。用50 μΐ HC1中止反應,且相對於650 nm在490 nm下讀出光學密 度。 結果(表1中所示)展示為彙集血清之中點力價。針對個 別血清分析,在30個樣品(1〇個為對照組)之中點力價上計 算 GMT 〇 表1 共輛物 抗PNAG中 點力償未吸收 抗PNAG中 點力償佐劑A dPNAG-TTOlO 1371 28465 dPNAG-TTOll 1133 40899 dPNAG-TT019 425 13429 dPNAG-TT020 656 10080 dPNAG-TT014 342 9806 dPNAG-TT017 203 8094 dPNAG-TT012 398 40509 dPNAG-TT016 719 7937 對照 50 50 119629.doc -35· 200815028 序列表 <ll〇> 1.比利時商葛蘭素史密斯克藍生物品公司 2.美國布萊翰婦女醫院 <120>共軛方法 <130>VB61918 <140〉096111419 <141〉2007-03-30 <150> 60/787,587 ; 0606416.6 ; 0606417.4 ; 60/787,249 <151> 2006-03-30 ; 2006-03-30 ; 2006-03-30 ; 2006-03-30 <160> 164 <170> FastSEQ for Windows Version 4.0
<210〉 1 <211〉 533 <212> PRT <213>葡萄球菌 <400〉 1
Leu Arg Phe Gly Asp Arg Lys Leu 10 15 Thr Glu Gly Asn Cys Tyr Gly Leu 25 30 Ser Thr Phe Leu Lys lie Leu Ser 45 His Val Ser Leu Gly Lys Asn Glu 60 His Tyr Ala Tyr Glu Asp Glu Arg 75 80 His Glu Arg Leu Tyr Glu Val Met 90 95 Lys Pro Asp Phe Ser Asp Glu Asp 105 110 Gly Glu Phe Ala Glu Met Asn Gly 125 Asn Leu Leu Ser Gly Leu Gly lie 140 Met Ala Glu Leu Glu Asn Asn Gin 155 160 Ser Leu Phe Gly Glu Pro Asp Val 170 175 Gly Leu Asp lie Pro Ala lie Ser 185 190 Phe Asp Asn Thr Val He Val Val 205 Asn Val Cys Thr His lie Ala Asp 220 Tyr Val Gly Asn Tyr Asp Phe Trp 235 240 Lys Met Ala Gin Glu Gin Asn Lys 250 255 Leu Gin Asp Phe He Ala Arg Phe 265 270 Gin Ala Thr Ser Arg Lys Lys Gin 285 He Gin Pro Ser Ser Arg Arg Tyr 300 Arg Glu lie Gly Asn Asp Leu Leu 315 320 lie Asp Gly Glu Lys Val Leu Asp 330 335 Asn Asp Lys Ala lie Leu lie Gly 345 350 Leu Leu Lys lie Leu Ala Gly Glu 365 Lys Trp Gly Val Thr Thr Ser Leu 380 Glu Phe Phe Glu Gly Val Asn Met 395 400 Tyr Ala Pro Glu Asp Glu Gin Thr 410 415 Gly Arg Met Leu Phe Ser Gly Glu
Met Leu Gin Val Thr Asp Val Ser 1 5
Phe Glu Asp Val Asn lie Lys Phe 20 lie Gly Ala Asn Gly Ala Gly Lys 35 40
Gly Glu Leu Asp Ser Gin Thr Gly 50 55
Arg Leu Ala Val Leu Lys Gin Asp 65 70
Val Leu Asp Val Val lie Lys Gly 85
Lys Glu Lys Asp Glu lie Tyr Met 100
Gly lie Arg Ala Ala Glu Leu Glu 115 120
Trp Asn Ala Glu Ala Asp Ala Ala 130 135
Asp Pro Thr Leu His Asp Lys Lys 145 150
Lys lie Lys Val Leu Leu Ala Gin 165
Leu Leu Leu Asp Glu Pro Thr Asn 180
Trp Leu Glu Asp Phe Leu lie Asn 195 200
Ser His Asp Arg His Phe Leu Asn 210 215
Leu Asp Phe Gly Lys He Lys Val 225 230
Tyr Gin Ser Ser Gin Leu Ala Gin 245
Lys Lys Glu Glu Lys Met Lys Glu 260
Ser Ala Asn Ala Ser Lys Ser Lys 275 280
Leu Glu Lys lie Glu Leu Asp Asp 290 295
Pro Phe Val Lys Phe Thr Pro Glu 305 310 lie Val Gin Asn Leu Ser Lys Thr 325
Asn Val Ser Phe Thr Met Asn Pro 340
Asp Ser Glu lie Ala Lys Thr Thr 355 360
Met Glu Pro Asp Glu Gly Ser Phe 370 375
Ser Tyr Phe Pro Lys Asp Asn Ser 385 390
Asn Leu Val Asp Trp Leu Arg Gin 405
Glu Thr Phe Leu Arg Gly Phe Leu 119629-序列表.doc 200815028 420 425 430
Glu Val Lys Lys Lys Ala Ser Val Leu Ser Gly Gly Glu Lys Val Arg 435 440 445
Cys Met Leu Ser Lys Met Met Leu Ser Ser Ala Asn Val Leu Leu Leu 450 455 460
Asp Glu Pro Thr Asn His Leu Asp Leu Glu Ser lie Thr Ala Val Asn 465 470 475 480
Asp Gly Leu Lys Ser Phe Lys Gly Ser lie lie Phe Thr Ser Tyr Asp 485 490 495
Phe Glu Phe lie Asn Thr lie Ala Asn Arg Val lie Asp Leu Asn Lys 500 505 510
Gin Gly Giy Val Ser Lys Glu lie Pro Tyr Glu Glu Tyr Leu Gin Glu 515 520 525 lie Gly Val Leu Lys 530
<210〉 2 <211> 535 <212> PRT <213〉葡萄球菌 <400> 2
Met Leu Gin Val Thr Asp Val Ser Leu Arg Phe Gly Asp Arg Lys Leu 1 5 10 15
Phe Glu Asp Val Asn lie Lys Phe Thr Glu Gly Asn Cys Tyr Gly Leu 20 25 30 lie Gly Ala Asn Gly Ala Gly Lys Ser Thr Phe Leu Lys lie Leu Ser 35 40 45
Gly Glu lie Asp Ser Gin Thr Gly His Val Ser Leu Gly Lys Asp Glu 50 55 60
Arg Ley Ala Val Leu Lys Gin Asp His Phe Ala Tyr Glu Asp Glu Arg 65 70 75 80
Val Leu Asp Val Val He Lys Gly His Glu Arg Leu Tyr Gin Val Met 85 90 95
Lys Glu Lys Asp Glu lie Tyr Met Lys Pro Asp Phe Ser Asp Glu Asp 100 105 110
Gly lie Arg Ala Ala Glu Leu Glu Gly Glu Phe Ala Glu Met Asn Gly 115 120 125
Trp Asn Ala Glu Ala Asp Ala Ala Asn Leu Leu Ser Gly Leu Gly lie 130 135 140
Glu Pro Asp Leu His Asp Lys Asn Met Ser Glu Leu Glu Asn Asn Gin 145 150 155 160
Lys Val Lys Val Leu Leu Ala Gin Ser Leu Phe Gly Asp Pro Asp Val 165 170 175
Leu Leu Leu Asp Glu Pro Thr Asn Gly Leu Asp lie Pro Ala lie Ser 180 185 190
Trp Leu Glu Asp Phe Leu He Asn Phe Glu Asn Thr Val He Val Val 195 200 205
Ser His Asp Arg His Phe Leu Asn Asn Yal Cys Thr His lie Ala Asp 210 215 220
Leu Asp Phe Gly Lys lie Lys Leu Tyr Val Gly Asn Tyr Asp Phe Trp 225 230 235 240
Tyr Gin Ser Ser Gin Leu Ala Gin Lys Met Ala Gin Glu Gin Asn Lys 245 250 255
Lys Lys Glu Glu Lys Met Lys Glu Leu Gin Asp Phe lie Ala Arg Phe 260 265 270
Ser Ala Asn Ala Ser Lys Ser Lys Gin Ala Thr Ser Arg Lys Lys Gin 275 280 285
Leu Glu Lys lie Glu Leu Asp Asp He Gin Pro Ser Ser Arg Arg Tyr 290 295 300
Pro Tyr Val Lys Phe Thr Pro Glu Arg Glu lie Gly Asn Asp Leu Leu 305 310 315 320
Thr Val Glu Asn Leu Ser Lys Thr lie Asp Gly Glu Lys Val Leu Asp 325 330 335
Asn Val Ser Phe Thr Met Asn Pro Asn Asp Lys Ala lie Leu Val Gly 340 345 350
Asp Ser Glu lie Ala Lys Thr Thr Leu Leu Lys lie Leu Ala Gly Glu 355 360 365
Met Glu Pro Asp Glu Gly Thr Phe Lys Trp Gly Val Thr Thr Ser Leu 370 375 380
Ser Tyr Phe Pro Lys Asp Asn Ser Glu Phe Phe Asp Gly Val Asp Met 385 390 395 400
Asn Leu Val Glu Trp Leu Arg Gin Tyr Ala Fro Glu Asp Glu Gin Thr 405 410 415 -2· 119629-序列表.doc 200815028
Glu Thr Phe Leu Arg Gly Phe Leu Gly Arg Met Leu Phe Ser Gly Glu 420 425 430
Glu Val Lys Lys Lys Ala Ser Val Leu Ser Gly Gly Glu Lys Val Arg •435 440 445
Cys Met Leu Ser Lys Met Met Leu Ser Ser Ala Asn Val Leu Leu Leu 450 455 460
Asp Glu Pro Thr Asn His Leu Asp Leu Glu Ser lie Thr Ala Val Asn 465 470 475 480
Asp Gly Leu Lys Ser Phe Lys Gly Ser He lie Phe Thr Ser Tyr Asp 485 490 495
Phe Glu Fhe He Asn Thr He Ala Asn Arg Val lie Asp Leu Asn Gin 500 505 510
Ala Gly Ala Leu Ser Lys Glu Val Pro Tyr Glu Glu Tyr Leu Gin Glu 515 520 525 lie Gly Val Leu Gin Asn Asn 530 535
〈210〉 3 <211〉 434 <212> PRT <213>葡萄球菌 <400> 3
Met Pro He He Thr Asp Val Tyr Ala Arg Glu Val Leu Asp Ser Arg 1 5 10 15
Gly Asn Pro Thr Val Glu Val Glu Val Leu Thr Glu Ser Gly Ala Phe 20 25 30
Gly Arg Ala Leu Val Pro Ser Gly Ala Ser Thr Gly Glu His Glu Ala 35 40 45
Val Glu Leu Arg Asp Gly Asp Lys Ser Arg Tyr Leu Gly Lys Gly Val 50 55 60
Thr Lys Ala Val Glu Asn Val Asn Glu lie He Ala Pro Glu lie lie 65 70 75 80
Glu Gly Glu Phe Ser Val Leu Asp Gin Val Ser He Asp Lys Met Met 85 90 95 lie Ala Leu Asp Gly Thr Pro Asn Lys Gly Lys Leu Gly Ala Asn Ala 100 105 110 lie Leu Gly Val Ser lie Ala Val Ala Arg Ala Ala Ala Asp Leu Leu 115 120 125
Gly Gin Pro Leu Tyr Lys Tyr Leu Gly Gly Phe Asn Gly Lys Gin Leu 130 135 140
Pro Val Pro Met Met Asn He Val Asn Gly Gly Ser His Ser Asp Ala 145 150 155 160
Pro He Ala Phe Gin Glu Phe Met lie Leu Pro Val Gly Ala Thr Thr 165 170 175
Phe Lys Glu Ser Leu Arg Trp Gly Thr Glu He Phe His Asn Leu Lys 180 185 190
Ser He Leu Ser Lys Arg Gly Leu Glu Thr Ala Val Gly Asp Glu Gly 195 200 205
Gly Phe Ala Pro Lys Phe Glu Gly Thr Glu Asp Ala Val Glu Thr lie 210 215 220
He Gin Ala lie Glu Ala Ala Gly Tyr Lys Pro Gly Glu Glu Val Phe 225 230 235 240
Leu Gly Phe Asp Cys Ala Ser Ser Glu Phe Tyr Glu Asn Gly Val Tyr 245 250 255
Asp Tyr Ser Lys Phe Glu Gly Glu His Gly Ala Lys Arg Thr Ala Ala 260 265 270
Glu Gin Val Asp Tyr Leu Glu Gin Leu Val Asp Lys Tyr Pro He He 275 280 285
Thr lie Glu Asp Gly Met Asp Glu Asn Asp Trp Asp Gly Trp Lys Gin 290 295 300
Leu Thr Glu Arg lie Gly Asp Arg Val Gin Leu Val Gly Asp Asp Leu 305 310 315 320
Phe Val Thr Asn Thr Glu lie Leu Ala Lys Gly He Glu Asn Gly lie 325 330 335
Gly Asn Ser lie Leu He Lys Val Asn Gin He Gly Thr Leu Thr Glu 340 345 350
Thr Phe Asp Ala He Glu Met Ala Gin Lys Ala Gly Tyr Thr Ala Val 355 360 365
Val Ser His Arg Ser Gly Glu Thr Glu Asp Thr Thr lie Ala Asp lie 370 375 380
Ala Val Ala Thr Asn Ala Gly Gin lie Lys Thr Gly Ser Leu Ser Arg 385 390 395 400
Thr Asp Arg lie Ala Lys Tyr Asn Gin Leu Leu Arg He Glu Asp Glu 119629-序列表.doc 200815028 405 410 415
Leu Phe Glu Thr Ala Lys Tyr Asp Gly lie Lys Ser Phe Tyr Asn Leu 420 425 430
Asp Lys
<210〉 4 <211> 434 <2I2> PRT <213>葡萄球菌 <400> 4
Met Pro lie lie Thr Asp Val Tyr Ala Arg Glu Val Leu Asp Ser Arg 1 5 10 15
Gly Asn Pro Thr Val Glu Val Glu Val Leu Thr Glu Ser Gly Ala Phe 20 25 30
Gly Arg Ala Leu Val Fro Ser Gly Ala Ser Thr Gly Glu His Glu Ala 35 40 45
Val Glu Leu Arg Asp Gly Asp Lys Ser Arg Tyr Leu Gly Lys Gly Val 50 55 60
Thr Lys Ala Val Glu Asn Val Asn Glu Met He Ala Pro Glu lie Val 65 70 75 80
Glu Gly Glu Phe Ser Val Leu Asp Gin Val Ser lie Asp Lys Met Met 85 90 95 lie Gin Leu Asp Gly Thr His Asn Lys Gly Lys Leu Gly Ala Asn Ala 100 105 110
He Leu Gly Val Ser lie Ala Val Ala Arg Ala Ala Ala Asp Leu Leu 115 120 125
Gly Gin Pro Leu Tyr Lys Tyr Leu Gly Gly Phe Asn Gly Lys Gin Leu 130 135 140
Pro Val Pro Met Met Asn lie Val Asn Gly Gly Ser His Ser Asp Ala 145 150 155 160
Pro lie Ala Phe Gin Glu Phe Met lie Leu Pro Val Gly Ala Glu Ser 165 170 175
Phe Lys Glu Ser Leu Arg Trp Gly Ala Glu lie Phe His Asn Leu Lys 180 185 190
Ser lie Leu Ser Glu Arg Gly Leu Glu Thr Ala Val Gly Asp Glu Gly 195 200 205
Gly Phe Ala Pro Arg Phe Glu Gly Thr Glu Asp Ala Val Glu Thr He 210 215 220 lie Lys Ala lie Glu Lys Ala Gly Tyr Lys Pro Gly Glu Asp Val Phe 225 230 235 240
Leu Gly Phe Asp Cys Ala Ser Ser Glu Phe Tyr Glu Asn Gly Val Tyr 245 250 255
Asp Tyr Thr Lys Phe Glu Gly Glu His Gly Ala Lys Arg Ser Ala Ala 260 265 270
Glu Gin Val Asp Tyr Leu Glu Glu Leu lie Gly Lys Tyr Pro lie lie 275 280 285
Thr lie Glu Asp Gly Met Asp Glu Asn Asp Trp Glu Gly Trp Lys Gin 290 295 300
Leu Thr Asp Arg lie Gly Asp Lys Val Gin Leu Val Gly Asp Asp Leu 305 310 315 320
Phe Val Thr Asn Thr Glu He Leu Ser Lys Gly lie Glu Gin Gly lie 325 330 335
Gly Asn Ser lie Leu lie Lys Val Asn Gin lie Gly Thr Leu Thr Glu 340 345 350
Thr Phe Asp Ala lie Glu Met Ala Gin Lys Ala Gly Tyr Thr Ala Val 355 360 365
Val Ser His Arg Ser Gly Glu Thr Glu Asp Thr Thr lie Ala Asp lie 370 375 380
Ala Val Ala Thr Asn Ala Gly Gin lie Lys Thr Gly Ser Leu Ser Arg 385 390 395 400
Thr Asp Arg lie Ala Lys Tyr Asn Gin Leu Leu Arg lie Glu Asp Glu 405 410 415
Leu Tyr Glu Thr Ala Lys Phe Glu Gly lie Lys Ser Phe Tyr Asn Leu 420 425 430
Asp Lys
<210〉 5 <211〉 255 <212〉 PRT 4- 119629-序列表.doc 200815028 <213〉葡萄球菌 <400> 5
Met Lys Lys lie Val Thr Ala Thr lie Ala Thr Ala Gly Leu Ala Thr 1 5 10 15
He Ala Phe Ala Gly His Asp Ala Gin Ala Ala Glu Gin Asn Asn Asn 20 25 30
Gly Tyr Asn Ser Asn Asp Ala Gin Ser Tyr Ser Tyr Thr *Fyr Thr lie 35 40 45
Asp Ala Gin Gly Asn Tyr His Tyr Thr Trp Thr Gly Asn Trp Asn Pro 50 55 60
Ser Gin Leu Thr Gin Asn Asn Thr Tyr Tyr Tyr Asn Asn Tyr Asn Thr 65 TO 75 80
Tyr Ser Tyr Asn Asn Ala Ser Tyr Asn Asn Tyr Tyr Asn His Ser Tyr 85 90 95
Gin Tyr Asn Asn Tyr Thr Asn Asn Ser Gin Thr Ala Thr Asn Asn Tyr 100 105 110
Tyr Thr Gly Gly Ser Gly Ala Ser Tyr Ser Thr Thr Ser Asn Asn Val 115 120 125
His Val Thr Thr Thr Ala Ala Pro Ser Ser Asn Gly Arg Ser lie Ser 130 135 140
Asn Gly Tyr Ala Ser Gly Ser Asn Leu Tyr Thr Ser Gly Gin Cys Thr 145 150 155 160
Tyr Tyr Val Phe Asp Arg Val Gly Gly Lys lie Gly Ser Thr Trp Gly 165 170 175
Asn Ala Ser Asn Trp Ala Asn Ala Ala Ala Ser Ser Gly Tyr Thr Val 180 185 190
Asn Asn Thr Pro Lys Val Gly Ala lie Met Gin Thr Thr Gin Gly Tyr 195 200 205
Tyr Gly His Val Ala Tyr Val Glu Gly Val Asn Ser Asn Gly Ser Vai 210 215 220
Arg Val Ser Glu Met Asn Tyr Gly His Gly Ala Gly Val Val Thr Ser 225 230 235 240
Arg Thr lie Ser Ala Asn Gin Ala Gly Ser Tyr Asn Phe lie His 245 250 255
<210> 6 <211> 267 <212> PRT <213>葡萄球菌 <400〉 6
Met Lys Lys lie Ala Thr Ala Thr lie Ala Thr Ala Gly Phe Ala Thr 1 5 10 15 lie Ala He Ala Ser Gly Asn Gin Ala His Ala Ser Glo Gin Asp Asn 20 25 30
Tyr Gly Tyr Asn Pro Asn Asp Pro Thr Ser Tyr Ser Tyr Thr Tyr Thr 35 40 45 lie Asp Ala Gin Gly Asn Tyr His Tyr Thr Trp Lys Gly Asn Trp His 50 55 60
Pro Ser Gin Leu Asn Gin Asp Asn Gly Tyr Tyr Ser Tyr Tyr Tyr Tyr 65 70 75 80
Asn Gly Tyr Asn Asn Tyr Asn Asn Tyr Asn Asn Gly Tyr Ser Tyr Asn 85 90 95
Asn Tyr Ser Arg Tyr Asn Asn Tyr Ser Asn Asn Asn Gin Ser Tyr Asn 100 105 110
Tyr Asn Asn 丁yr Asn Ser Tyr Asn Thr Asn Ser Tyr Arg Thr Gly Gly 115 120 125
Leu Gly Ala Ser Tyr Ser Thr Ser Ser Asn Asn Val Gin Val Thr Thr 130 135 140
Thr Met Ala Pro Ser Ser Asn Gly Arg Ser lie Ser Ser Gly Tyr Thr 145 150 155 160
Ser Gly Arg Asn Leu Tyr Thr Ser Gly Gin Cys Thr Tyr Tyr Val Phe 165 170 175
Asp Arg Val Gly Gly Lys lie Gly Ser Thr Trp Gly Asn Ala Ser Asn 180 185 190
Trp Ala Asn Ala Ala Ala Arg Ala Gly Tyr Thr Val Asn Asn Thr Pro 195 200 205
Lys Ala Gly Ala lie Met Gin Thr Thr Gin Gly Ala Tyr Gly His Val 210 215 220
Ala Tyr Val Glu Ser Val Asn Ser Asn Gly Ser Val Arg Val Ser Glu 225 230 235 240
Met Asn Tyr Gly Tyr Gly Pro Gly Val Val Thr Ser Arg Thr lie Ser 245 250 255 119629-序列表.doc 200815028
Ala Ser Gin Ala Ala Gly Tyr Asn Phe lie His 260 265 <210〉 7 <211> 257 <212> PRT <213〉葡觀求菌 <400> 7
Met Lys Lys He Ala Thr Ala Thr He Ala Thr Ala Gly lie Ala Thr 1 5 10 15
Phe Ala Phe Ala His His Asp Ala Gin Ala Ala Glu Gin Asn Asn Asp 20 25 30
Gly Tyr Asn Pro Asn Asp Pro Tyr Ser Tyr Ser Tyr Thr Tyr Thr He 35 40 45
Asp Ala Glu Gly Asn Tyr His Tyr Thr Trp Lys Gly Asn Trp Ser Pro 50 55 60
Asp Arg Val Asn Thr Ser Tyr Asn Tyr Asn Asn Tyr Asn Asn Tyr Asn 65 70 75 80
Tyr Tyr Gly Tyr Asn Asn Tyr Ser Asn Tyr Asn Asn Tyr Ser Asn Tyr 85 90 95
Asn Asn Tyr Asn Asn Tyr Gin Ser Asn Asn Thr Gin Ser Gin Arg Thr 100 105 110
Thr Gin Pro Thr Gly Gly Leu Gly Ala Ser Tyr Ser Thr Ser Ser Ser 115 120 125
Asn Val His Val Thr Thr Thr Ser Ala Pro Ser Ser Asn Gly Val Ser 130 135 140
Leu Ser Asn Ala Arg Ser Ala Ser Gly Asn Leu Tyr Thr Ser Gly Gin 145 150 155 160
Cys Thr Tyr Tyr Val Phe Asp Arg Val Gly Gly Lys lie Gly Ser Thr 165 170 175
Trp Gly Asn Ala Asn Asn Trp Ala Asn Ala Ala Ala Arg Ser Gly Tyr 180 185 190
Thr Val Asn Asn Ser Pro Ala Lys Gly Ala He Leu Gin Thr Ser Gin 195 200 205
Gly Ala Tyr Gly His Val Ala Tyr Val Glu Gly Val Aso Ser Asn Gly 210 215 220
Ser lie Arg Val Ser Glu Met Asn Tyr Gly His Gly Ala Gly Val Val 225 230 235 240
Thr Ser Arg Thr lie Ser Ala Ser Gin Ala Ala Ser Tyr Asn Tyr lie 245 250 255
His <210〉 8 <211> 309 <212> PRT <213〉葡萄球菌 <400> 8
Met Lys Lys Leu Val Pro Leu Leu Leu Ala Leu Leu Leu Leu Val Ala 1 5 10 15
Ala Cys Gly Thr Gly Gly Lys Gin Ser Ser Asp Lys Ser Asn Gly Lys 20 25 30
Leu Lys Val Val Thr Thr Asn Ser lie Leu Tyr Asp Met Ala Lys Asn 35 4〇 45
Val Gly Gly Asp Asn Val Asp lie His Ser lie Val Fro Val Gly Gin 50 55 60
Asp Pro His Glu Tyr Glu Val Lys Pro Lys Asp lie Lys Lys Leu Thr 65 70 75 80
Asp Ala Asp Val lie Leu Tyr Asn Gly Leu Asn Leu Glu Thr Gly Asn 85 90 95
Gly Trp Phe Glu Lys Ala Leu Glu Gin Ala Gly Lys Ser Leu Lys Asp 100 105 110
Lys Lys Val lie Ala Val Ser Lys Asp Val Lys Pro lie Tyr Leu Asn 115 120 125
Gly Glu Glu Gly Asn Lys Asp Lys Gin Asp Fro His Ala Trp Leu Ser 130 135 140
Leu Asp Asn Gly lie Lys Tyr Val Lys Thr lie Gin Gin Thr Phe lie 145 150 155 160
Asp Asn Asp Lys Lys His Lys Ala Asp Tyr Glu Lys Gin Gly Asn Lys 165 170 175 -6- 119629-序列表.doc 200815028
Tyr lie Ala Gin Leu Glu Lys Leu Asn Asn Asp Ser Lys Asp Lys Fhe 180 185 190
Asn Asp lie Pro Lys Glu Gin Arg Ala Met He Thr Ser Glu Gly Ala 195 200 205
Phe Lys 了yr Phe Ser Lys Gin Tyr Gly lie Thr Pro Gly Tyr lie Trp 210 215 220
Glu lie Asn Thr Glu Lys Gin Gly Thr Pro Glu Gin Met Arg Gin Ala 225 230 235 240 lie Glu Phe Val Lys Lys His Lys Leu Lys His Leu Leu Val Glu Thr 245 250 255
Ser Val Asp Lys Lys Ala Met Glu Ser Leu Ser Glu Glu Thr Lys Lys 260 265 270
Asp lie Phe Gly Glu Val Tyr Thr Asp Ser lie Gly Lys Glu Gly Thr 275 280 285
Lys Gly Asp Ser Tyr Tyr Lys Met Met Lys Ser Asn lie Glu Thr Val 290 295 300
His Gly Ser Met Lys 305
<210〉 9 <211> 309 <212> PRT <213>葡萄球菌 <400> 9
Met Lys Lys lie Leu Ala Leu Ala lie Ala Phe Leu lie lie Leu Ala 1 5 10 15
Ala Cys Gly Asn His Ser Asn His Glu His His Sex His Glu Gly Lys 20 25 30
Leu Lys Val Val Thr Thr Asn Ser lie Leu Tyr Asp Met Val Lys Arg 35 40 45
Val Gly Gly Asn Lys Val Asp Val His Ser He Val Pro Val Gly Gin 50 55 60
Asp Pro His Glu Tyr Glu Val Lys Pro Lys Asp lie Lys Ala Leu Thr 65 70 75 80
Asp Ala Asp Val Val Phe Tyr Asn Gly Leu Asn Leu Glu Thr Gly Asn 85 90 95
Gly Trp Phe Glu Lys Ala Leu Asp Gin Ala Gly Lys Ser Thr Lys Asp 100 105 110
Lys Asn Val lie Ala Ala Ser Asn Asn Val Lys Pro He Tyr Leu Asn 115 120 125
Gly Glu Glu Gly Asn Lys Asn Lys Gin Asp Pro His Ala Trp Leu Ser 130 135 140
Leu Glu Asn Gly lie Lys Tyr Val Lys Thr lie Gin Lys Ser Leu Glu 145 150 155 160
His His Asp Lys Lys Asp Lys Ser Thr Tyr Glu Lys Gin Gly Asn Ala 165 170 175
Tyr lie Ser Lys Leu Glu Glu Leu Asn Lys Asp Ser Lys Asn Lys Phe 180 185 190
Asp Asp lie Pro Lys Asn Gin Arg Ala Met Met Thr Ser Glu Gly Ala 195 200 205
Phe Lys Tyr Phe,Ala Gin Gin Phe Asp Val Lys Pro Gly Tyr lie Trp 210 215 220
Glu lie Asn Thr Glu Lys Gin Gly Thr Pro Gly Gin Met Lys Gin Ala 225 230 235 240 lie Lys Phe Val Lys Asp Asn His Leu Lys His Leu Leu Val Glu Thr 245 250 255
Ser Val Asp Lys Lys Ala Met Gin Ser Leu Ser Glu Glu Thr Lys Lys 260 265 270
Asp lie Tyr Gly Glu Val Phe Thr Asp Ser lie Gly Lys Glu Gly Thr 275 280 285
Lys Gly Asp Ser Tyr Tyr Lys Wet Met Lys Ser Asn lie Asp Thr lie 290 295 300
His Gly Ser Met Lys 305 <210> 10 <211> 233 <212> PRT <213〉麵球菌 <400> 10
Met Lys Lys Thr lie Met Ala Ser Ser Leu Ala Val Ala Leu Gly Val 119629·序列表.doc 200815028 1 5 10 15
Thr Gly Tyr Ala Ala Gly Thr Gly His Gin Ala His Ala Ala Glu Val 20 25 30
Asn Val Asp Gin Ala His Leu Val Asp Leu Ala His Asn His Gin Asp 35 40 45
Gin Leu Asn Ala Ala Pro lie Lys Asp Gly Ala Tyr Asp He His Fhe 50 55 60
Val Lys Asp Gly Phe Gin Tyr Asn Phe Thr Ser Asn Gly Thr Thr Trp 65 70 75 80
Ser Trp Ser Tyr Glu Ala Ala Asn Gly Gin Thr Ala Gly Phe Ser Asn 85 90 95
Val Ala Gly Ala Asp Tyr Thr Thr Ser Tyr Asn Gin Gly Ser Asp Val 100 105 110
Gin Ser Val Ser Tyr Asn Ala Gin Ser Ser Asn Ser Asn Val Glu Ala 115 120 125
Val Ser Ala Pro Thr Tyr His Asn Tyr Ser Thr Ser Thr Thr Ser Ser 130 135 140
Ser Val Arg Leu Ser Asn Gly Asn Thr Ala Gly Ala Thr Gly Ser Ser 145 150 155 160
Ala Ala Gin lie Met Ala Gin Arg Thr Gly Val Ser Ala Ser Thr Trp 165 170 175
Ala Ala He lie Ala Arg Glu Ser Asn Gly Gin Val Asn Ala Tyr Asn 180 185 190
Pro Ser Gly Ala Ser Gly Leu Phe Gin Thr Met Pro Gly Trp Gly Pro 195 200 205
Thr Asn Thr Val Asp Gin Gin lie Asn Ala Ala Val Lys Ala Tyr Lys 210 215 220
Ala Gin Gly Leu Gly Ala Trp Gly Phe 225 230 <210〉 11 <211> 235 <212〉 PRT <213〉葡萄球菌 <400> 11
Met Lys Lys Thr Val lie Ala Ser Thr Leu Ala Val Ser Leu Gly lie 15 10 15
Ala Gly Tyr Gly Leu Ser Gly His Glu Ala His Ala Ser Glu Thr Thr 20 25 30
Asn Val Asp Lys Ala His Leu Val Asp Leu Ala Gin His Asn Pro Glu 35 40 45
Glu Leu Asn Ala Lys Pro Val Gin Ala Gly Ala Tyr Asp lie His Phe 50 55 60
Val Asp Asn Gly Tyr Gin Tyr Asn Phe Thr Ser Asn Gly Ser Glu Trp 65 70 75 80
Ser Trp Ser Tyr Ala Val Ala Gly Ser Asp Ala Asp Tyr Thr Glu Ser 85 90 95
Ser Ser Asn Gin Glu Val Ser Ala Asn Thr Gin Ser Ser Asn Thr Asn 100 105 110
Val Gin Ala Val Ser Ala Pro Thr Ser Ser Glu Ser Arg Ser Tyr Ser 115 120 125
Thr Ser Thr Thr Ser Tyr Ser Ala Pro Ser His Asn Tyr Ser Ser His 130 135 140
Ser Ser Ser Val Arg Leu Ser Asn Gly Asn Thr Ala Gly Ser Val Gly 145 150 155 160
Ser Tyr Ala Ala Ala Gin Met Ala Ala Arg Thr Gly Val Ser Ala Ser 165 170 175
Thr Trp Glu His lie lie Ala Arg Glu Ser Asn Gly Gin Leu His Ala 180 185 190
Arg Asn Ala Ser Gly Ala Ala Gly Leu Phe Gin Thr Met Pro Gly Trp 195 200 205
Gly Ser Thr Gly Ser Vai Asn Asp Gin lie Asn Ala Ala Tyr Lys Ala 210 215 220
Tyr Lys Ala Gin Gly Leu Ser Ala Trp Gly Met 225 230 235 〈210〉 12 <211> 3890 <212> PRT <213〉葡萄球菌 <400> 12 8- 119629-序列表.doc 200815028
Met Asn Tyr Arg Asp Lys He Gin Lys Phe Ser lie Arg Lys Tyr Thr 15 10 15
Val Gly Thr Phe Ser Thr Val lie Ala Thr Leu Val Phe Leu Gly Phe 20 25 30
Asn Thr Ser Gin Ala His Ala Ala Glu Thr Asn Gin Pro Ala Ser Val 35 40 45
Val Lys Gin Lys Gin Gin Ser Asn Asn Glu Gin Thr Glu Asn Arg Glu 50 55 60
Ser Gin Val Gin Asn Ser Gin Asn Ser Gin Asn Ser Gin Ser Leu Ser 65 70 75 80
Ala Thr His Glu Asn Glu Gin Pro Asn Asn Ser Gin Ala Asn Leu Val 85 90 95
Asn Gin Lys Val Ala Gin Ser Ser Thr Thr Asn Asp Glu Gin Pro Ala 100 105 110
Ser Gin Asn Val Asn Thr Lys Lys Asp Ser Ala Thr Ala Ala Thr Thr 115 120 125
Gin Fro Asp Lys Glu Glu Ser Lys His Lys Gin Asn Glu Ser Gin Ser 130 135 140
Ala Asn Lys Asn Gly Asn Asp Asn Arg Ala Ala His Val Glu Asn His 145 150 155 160
Glu Ala Asn Val Val Thr Ala Ser Asp Ser Ser Asp Asn Gly Asn Val 165 170 175
Gin His Asp Arg Asn Glu Leu Gin Ala Phe Phe Asp Ala Asn Tyr His 180 185 190
Asp Tyr Arg Phe He Asp Arg Glu Asn Ala Asp Ser Gly Thr Phe Asn 195 200 205
Tyr Val Lys Gly lie Phe Asp Lys lie Asn Thr Leu Leu Gly Ser Asn 210 215 220
Asp Pro He Asn Asn Lys Asp Leu Gin Leu Ala Tyr Lys Glu Leu Glu 225 230 235 240
Gin Ala Val Ala Leu lie Arg Thr Met Pro Gin Arg Gin Gin Thr Sex 245 250 255
Arg Arg Ser Asn Arg He Gin Thr Arg Ser Val Glu Ser Arg Ala Ala 260 265 270
Glu Pro Arg Ser Val Ser Asp Tyr Gin Asn Ala Asn Ser Ser Tyr Tyr 275 280 285
Val Glu Asn Ala Asn Asp Gly Ser Gly Tyr Fro Val Gly Thr Tyr lie 290 295 300
Asn Ala Ser Ser Lys Gly Ala Pro Tyr Asn Leu Pro Thr Thr Pro Trp 305 310 315 320
Asn Thr Leu Lys Ala Ser Asp Ser Lys Glu lie Ala Leu Met Thr Ala 325 330 335
Lys Gin Thr Gly Asp Gly Tyr Gin Trp Val He Lys Phe Asn Lys Gly 340 345 350
His Ala Pro His Gin Asn Met lie Phe Trp Phe Ala Leu Pro Ala Asp 355 360 365
Gin Val Pro Val Gly Arg Thr Asp Phe Val Thr Val Asn Ser Asp Gly 370 375 380
Thr Asn Val Gin Trp Ser His Gly Ala Gly Ala Gly Ala Asn Lys Pro 385 390 395 400
Leu Gin Gin Met Trp Glu Tyr Gly Val Asn Asp Pro Asp Arg Ser His 405 410 415
Asp Phe Lys lie Arg Asn Arg Ser Gly Gin Val He Tyr Ser Trp Pro 420 425 430
Thr Val His Val Tyr Ser Leu Glu Asp Leu Ser Arg Ala Ser Asp Tyr 435 440 445
Phe Ser Glu Ala Gly Ala Thr Pro Ala Thr Lys Ala Phe Gly Arg Gin 450 455 460
Asn Phe Glu Tyr lie Asn Gly Gin Lys Pro Ala Glu Ser Pro Gly Val 465 470 475 480
Pro Lys Val Tyr Thr Phe He Gly Gin Gly Asp Ala Ser Tyr Thr lie 485 490 495
Ser Phe Lys Thr Gin Gly Pro Thr Val Asn Lys Leu Tyr Tyr Ala Ala 500 505 510
Gly Gly Arg Ala Leu Glu Tyr Asn Gin Leu Phe Met Tyr Ser Gin Leu 515 520 525
Tyr Val Glu Ser Thr Gin Asp His Gin Gin Arg Leu Asn Gly Leu Arg 530 535 540
Gin Val Val Asn Arg Thr Tyr Arg lie Gly Thr Thr Lys Arg Val Glu 545 550 555 560
Val Ser Gin Gly Asn Val Gin Thr Lys Lys Val Leu Glu Ser Thr Asn 565 570 575
Leu Asn lie Asp Asp Phe Val Asp Asp Pro Leu Ser Tyr Val Lys Thr 580 585 590
Pro Ser Asn Lys Val Leu Gly Phe Tyr Pro Thr Asn Ala Asn Thr Asn 119629-序列表.doc 200815028 595 600 605
Ala Phe Arg Pro Gly Gly Val Gin Glu Leu Asn Glu Tyr Gin Leu Ser 610 615 620
Gin Leu Phe Thr Asp Gin Lys Leu Gin Glu Ala Ala Arg Thr Arg Asn 625 630 635 640
Pro lie Arg Leu Met lie Gly Phe Asp Tyr Pro Asp Gly Tyr Gly Asn 645 650 655
Ser Glu Thr Leu Val Pro Val Asn Leu Thr Val Leu Pro Glu lie Gin 660 665 670
His Asn lie Lys Phe Phe Lys Asn Asp Asp Thr Gin Asn He Ala Glu 675 680 685
Lys Pro Phe Ser Lys Gin Ala Gly His Pro Val Phe Tyr Val Tyr Ala 690 695 700
Gly Asn Gin Gly Asn Ala Ser Val Asn Leu Gly Gly Ser Val Thr Ser 705 710 715 720 lie Gin Pro Leu Arg lie Asn Leu Thr Ser Asn Glu Asn Phe Thr Asp 725 730 735
Lys Asp Trp Gin lie Thr Gly lie Pro Arg Thr Leu His lie Glu Asn 740 745 750
Ser Thr Asn Arg Thr Asn Asn Ala Arg Glu Arg Asn lie Glu Leu Val 755 760 765
Gly Asn Leu Leu Pro Gly Asp Tyr Phe Gly Thr lie Arg Fhe Gly Arg 770 775 780
Lys Glu Gin Leu Phe Glu lie Arg Val Lys Pro His Thr Pro Thr lie 785 790 795 800
Thr Thr Thr Ala Glu Gin Leu Arg Gly Thr Ala Leu Gin Lys Yal Pro 805 810 815
Val Asn He Ser Gly lie Pro Leu Asp Pro Ser Ala Leu Val Tyr Leu 820 825 830
Val Ala Pro Thr Asn Gin Thr Thr Asn Gly Gly Ser Glu Ala Asp Gin 835 840 845 lie Pro Ser Gly Tyr Thr lie Leu Ala Thr Gly Thr Pro Asp Gly Val 850 855 860
His Asn Thr lie Thr lie Arg Pro Gin Asp Tyr Val Val Phe lie Pro 865 870 875 880
Pro Val Gly Lys Gin lie Arg Ala Val Val Tyr Tyr Asn Lys Val Val 885 890 895
Ala Ser Asn Met Ser Asn Ala Val Thr lie Leu Pro Asp Asp lie Pro 900 905 910
Pro Thr lie Asn Asn Pro Val Gly He Asn Ala Lys Tyr Tyr Arg Gly 915 920 925
Asp Glu Val Asn Phe Thr Met Gly Val Ser Asp Arg His Ser Gly lie 930 935 940
Lys Asn Thr Thr He Thr Thr Leu Pro Ser Gly Trp Thr Ser Asn Leu 945 950 955 960
Thr Lys Ser Asp Asn Lys Asn Gly Ser Leu Ala He Thr Gly Arg Val 965 970 975
Ser Met Asn Gin Ala Phe Asn Ser Asp lie Thr Phe Lys Val Ser Ala 980 985 990
Thr Asp Asn Yal Asn Asn Thr Thr Asn Asp Ser Gin Ser Lys His Val 995 1000 1005
Ser lie His Val Gly Lys lie Ser Glu Asp Ala His Pro He Val Leu 1010 1015 1020
Gly Asn Thr Glu Lys Val Val Val Val Asn Pro Thr Ala Val Ser Asn 1025 1030 1035 1040
Asp Glu Lys Gin Ser lie lie Thr Ala Phe Met Asn Lys Asn Gin Asn 1045 1050 1055 lie Arg Gly Tyr Leu Ala Ser Thr Asp Pro Val Thr Val Asp Asn Asn 1060 1065 1070
Gly Asn Val Thr Leu His Tyr Arg Asp Gly Ser Ser Thr Thr Leu Asp 1075 1080 1085
Ala Thr Asn Val Met Thr Tyr Glu Pro Val Val Lys Ser Glu Tyr Gin 1090 1095 1100
Thr A】a Asn Ala Ala Lys Thr Ala 丁hr Val Thr lie Ala Lys Gly Gin 1105 1110 1115 1120
Ser Phe Asn lie Gly Asp lie Lys Gin Tyr Phe Thr Leu Ser Asn Gly 1125 1130 1135
Gin Ala lie Pro Asn Gly Thr Phe Thr Asn lie Thr Ser Asp Arg Thr 1140 1145 1150 lie Pro Thr Ala Gin Glu Val Ser Gin Met Asn Ala Gly Thr Gin Leu 1155 1160 1165
Tyr His lie Val Ala Ser Asn Ala Tyr His Lys Asp Thr Glu Asp Phe 1170 1175 1180
Tyr lie Ser Leu Lys lie Val Asp Val Lys Gin Fro Glu Gly Asp Gin 1185 1190 1195 1200 10 119629-序列表.doc 200815028
Arg Val Tyr Arg Thr Ser Thr Tyr Asp Leu Thr Thr Asp Glu lie Ser 1205 1210 1215
Lys Val Lys Gin Ala Phe lie Asn Ala Asn Arg Asp. Val lie Thr Leu 1220 1225 1230
Ala Glu Gly Asp lie Ser Val Thr Asn Thr Pro Asn Gly Ala Asn Val 1235 1240 1245
Ser Thr lie Thr Val Asn lie Asn Lys Gly Arg Leu Thr Lys Ser Phe 1250 1255 1260
Ala Ser Asn Leu Ala Asn Met Asn Phe Leu Arg Trp Val Asn Phe Pro 1265 1270 1275 1280
Gin Asp Tyr Thr Val Thr Trp Thr Asn Ala Lys lie Ala Asn Arg Pro 1285 1290 1295
Thr Asp Gly Gly Leu Ser 了rp Ser Asp Asp His Lys Ser Leu lie Tyr 1300 1305 1310
Arg Tyr Asp Ala Thr Leu Gly Thr Gin lie Thr Thr Asn Asp lie Leu 1315 1320 1325
Thr Met Leu Lys Ala Thr Thr Thr Val Pro Gly Leu Arg Asn Asn lie 1330 1335 1340
Thr Gly Asn Glu Lys Ala Gin Ala Glu Ala Gly Gly Arg Pro Asn Tyr 1345 1350 1355 1360
Arg Thr Thr Gly Tyr Ser Gin Ser Asn Ala Thr Thr Asp Gly Gin Arg 1365 1370 1375
Gin Phe Thr Leu Asn Gly Gin Val He Gin lie Leu Asp He lie Asn 1380 1385 1390
Pro Ser Asn Gly Tyr Gly Gly Gin Pro Val Thr Asn Ser Asn Thr Arg 1395 1400 1405
Ala Asn His Ser Asn Ser Thr Val Val Asn Val Asn Glu Pro Ala Ala 1410 1415 1420
Asn Gly Ala Gly Ala Phe Thr He Asp His Val Val Lys Ser Asn Ser 1425 1430 1435 1440
Thr His Asn Ala Ser Asp Ala Val Tyr Lys Ala Gin Leu Tyr Leu Thr 1445 1450 1455
Pro Tyr Gly Pro Lys Gin Tyr Val Glu His Leu Asn Gin Asn Thr Gly 1460 1465 1470
Asn Thr Thr Asp Ala lie Asn lie Tyr Phe Val Pro Ser Asp Leu Val 1475 1480 1485
Asn Pro Thr lie Ser Val Gly Asn Tyr Thr Asn His Gin Val Phe Ser 1490 1495 1500
Gly Glu Thr Phe Thr Asn Thr lie Thr Ala Asn Asp Asn Phe Gly Val 1505 1510 1515 1520
Gin Ser Val Thr Val Pro Asn Thr Ser Gin lie Thr Gly Thr Val Asp 1525 1530 1535
Asn Asn His Gin His Val Ser Ala Thr Ala Pro Asn Val Thr Ser Ala 1540 1545 1550
Thr Ser Lys Thr lie Asn Leu Leu Ala Thr Asp Thr Ser Gly Asn Thr 1555 1560 1565
Ala Thr Thr Ser Phe Asn Val Thr Val Lys Pro Leu Arg Asp Lys Tyr 1570 1575 1580
Arg Val Gly Thr Ser Ser Thr Ala Ala Asn Pro Val Arg lie Ala Asn 1585 1590 1595 1600 lie Ser Asn Asn Ala Thr Val Ser Gin Ala Asp Gin Thr Thr lie lie 1605 1610 1615
Asn Ser Leu Thr Phe Thr Ser Asn Ala Pro Asn Arg Asn Tyr Ala Thr 1620 1625 1630
Ala Ser Ala Asn Glu He Thr Ser Lys Thr Val Ser Asn Val Ser Arg 1635 1640 1645
Thr Gly Asn Asn Ala Asn Val Thr Val Thr Val Thr His Gin Asp Gly 1650 1655 1660
Thr Thr Ser Thr Val Thr Val Pro Val Lys His Val He Pro Glu lie 1665 1670 1675 1680
Val Ala His Ser His Tyr Thr Val Gin Gly Gin Asp Phe Pro Ala Gly 1685 1690 1695
Asn Gly Ser Ser Ala Ala Asp Tyr Phe Lys Leu Ser Asn Gly Ser Ala 1700 1705 1710 lie Pro Asp Ala Thr lie Thr Trp Val Ser Gly Gin Ala Pro Asn Lys 1715 1720 1725
Asp Asn Thr Arg lie Gly Glu Asp lie Thr Val Thr Ala His He Leu 1730 1735 1740 lie Asp Gly Glu Thr Thr Pro lie Thr Lys Thr Ala Thr Tyr Lys Val 1745 1750 1755 1760
Val Arg Thr Val Pro Lys His Val Phe Glu Thr Ala Arg Gly Val Leu 1765 1770 1775
Tyr Pro Gly Val Ser Asp Met Tyr Asp Ala Lys Gin Tyr Val Lys Pro 1780 1785 1790
Val Asn Asn Ser Trp Ser Thr Asn Ala Gin His Met Asn Phe Gin Phe 11- 119629-序列表.doc 200815028 1795 1800 1805
Val Gly Thr Tyr Gly Pro Asn Lys Asp Val Val Gly He Ser Thr Arg 1810 1815 1820
Leu lie Arg Val Thr Tyr Asp Asn Arg Gin Thr Glu Asp Leu Thr lie 1825 1830 1835 1840
Leu Ser Lys Val Lys Pro Asp Pro Pro Arg He Asp Ala Asn Ser Val 1845 1850 1855
Thr Tyr Lys Ala Gly Leu Thr Asn Gin Glu He Lys Val Asn Asn Val 1860 1865 1870
Leu Asn Asn Ser Ser Val Lys Leu Phe Lys Ala Asp Asn Thr Pro Leu 1875 1880 1885
Asn Val Thr Asn lie Thr His Gly Ser Gly Phe Ser Ser Val Val Thr 1890 1895 1900
Val Ser Asp Ala Leu Pro Asn Gly Gly lie Lys Ala Lys Ser Ser lie 1905 1910 1915 1920
Ser Met Asn Asn Val Thr Tyr Thr Thr Gin Asp Glu His Gly Gin Val 1925 1930 1935
Val Thr Val Thr Arg Asn Glu Ser Val Asp Ser Asn Asp Ser Ala Ser 1940 1945 1950
Val Thr Val Thr Pro Gin Leu Gin Ala Thr Thr Glu Gly Ala Vai Phe 1955 1960 1965 lie Lys Gly Gly Asp Gly Phe Asp Phe Gly His Val Glu Arg Phe lie 1970 1975 1980
Gin Asn Fro Pro His Gly Ala Thr Val Ala Trp His Asp Ser Pro Asp 1985 1990 1995 2000
Thr Trp Lys Asn Thr Val Gly Asn Thr His Lys Thr Ala Val Val Thr 2005 2010 2015
Leu Fro Ser Gly Gin Gly Thr Arg Asn Val Glu Val Pro Val Lys Val 2020 2025 2030
Tyr Pro Val Ala Asn Ala Lys Ala Pro Ser Arg Asp Val Lys Gly Gin 2035 2040 2045
Asn Leu Thr His Gly Thr Asn Ala lie Asp Tyr lie Thr Phe Asp Fro 2050 2055 2060
Asn Thr Asn Thr Asn Gly He Thr Ala Ala Trp Ala Asn Arg Gin Gin 2065 2070 2075 2080
Pro Asn Asn Gin Gin Ala Gly Val Gin His Leu Asn Val Asp Val Thr 2085 2090 2095
Tyr Pro Gly He Ser Ala Ala Lys Arg Val Pro Val Thr Val Asn Val 2100 2105 2110
Tyr Gin Phe Glu Phe Pro Gin Thr Thr Tyr Thr Thr Thr Val Gly Gly 2115 2120 2125
Thr Leu Ala Ser Gly Thr Gin Ala Ser Gly Tyr Ala His Met Gin Asn 2130 2135 2140
Ala Ser Gly Leu Pro Thr Asp Gly Phe Thr Tyr Lys Trp Asn Arg Asp 2145 2150 2155 2160
Thr Thr Gly Thr Asn Asp Ala Asn Trp Ala Ala Met Asn Lys Pro Asn 2165 2170 2175
Thr Ala Gin Val Val Asn Ala Lys Tyr Asp Val lie Tyr Asn Gly His 2180 2185 2190
Thr Phe Ala Thr Ser Leu Pro Ala Lys Phe Val Val Lys Asp Val Gin 2195 2200 2205
Fro Ala Lys Pro Thr Val Thr Glu Thr Ala Ala Gly Ala lie Thr lie 2210 2215 2220
Ala Pro Gly Ala Asn Gin Thr Val Asn Thr His Ala Gly Asn Val Thr 2225 2230 2235 2240
Thr Tyr Ala Asp Lys Leu Val lie Lys Arg Asn Gly Asn Val Val Thr 2245 2250 2255
Thr Phe Thr Arg Arg Asn Asn Thr Ser Pro Trp Val Lys Glu Ala Ser 2260 2265 2270
Ala Asp Asn Val Thr Gly Ila Val Gly Thr Asn Asn Gly lie Thr Val 2275 2280 2285
Ala Ala Gly Thr Phe Asn Fro Ala Asp Thr lie Gin Val Val Ala Thr 2290 2295 2300
Gin Gly Ser Gly Glu Thr lie Ser Asp Glu Gin Arg Ser Asp Asp Phe 2305 2310 2315 2320
Thr Val Val Ala Pro Gin Pro Asn Gin Ala Thr Thr Lys lie Trp Gin 2325 2330 2335
Asn Gly His lie Asp lie Thr Pro Asn Asn Pro Ser Gly His Leu lie 2340 2345 2350
Asn Pro Thr Gin Ala Met Asp lie Ala Tyr Thr Glu Lys Val Gly Asn 2355 2360 2365
Gly Ala Glu His Ser Lys Thr lie Asn Val Val Arg Gly Gin Asn Asn 2370 2375 2380
Gin Trp Thr lie Ala Asn Lys Pro Asp Tyr Val Thr Leu Asp Ala Gin 12- 119629·序列表.doc 200815028 2385 2390 2395 2400
Thr Gly Lys Val Thr Phe Asn Ala Asn Thr lie Lys Pro Asn Ser Ser 2405 2410 2415 lie Thr lie Thr Pro Lys Ala Gly Thr Gly His Ser Val Ser Ser Asn 2420 2425 2430
Pro Ser Thr Leu Thr Ala Pro Ala Ala His Thr Val Asn Thr Thr Glu 2435 2440 2445 lie Val Lys Asp Tyr Gly Ser Asn Val Thr Ala Ala Glu lie Asn Asn 2450 2455 2460
Ala Val Gin Val Ala Asn Lys Arg Thr Ala Thr He Lys Asn Gly Thr 2465 2470 2475 2480
Ala Met Pro Thr Asn Leu Ala Gly Gly Ser Thr Thr Thr lie Pro Val 2485 2490 2495
Thr Val Thr Tyr Asn Asp Gly Ser Thr Glu Glu Val Gin Glu Ser lie 2500 2505 2510
Phe Thr Lys Ala Asp Lys Arg Glu Leu lie Thr Ala Lys Asn His Leu 2515 2520 2525
Asp Asp Pro Val Ser Thr Glu Gly Lys Lys Pro Gly Thr lie Thr Gin 2530 2535 2540
Tyr Asn Asn Ala Met His Asn Ala Gin Gin Gin He Asn Thr Ala Lys 2545 2550 2555 2560
Thr Glu Ala Gin Gin Val He Asn Asn Glu Arg Ala Thr Pro Gin Gin 2565 2570 2575
Val Ser Asp Ala Leu Thr Lys Val Arg Ala Ala Gin Thr Lys He Asp 2580 2585 2590
Gin Ala Lys Ala Leu Leu Gin Asn Lys Glu Asp Asn Ser Gin Leu Val
2595 2600 2605
Thr Ser Lys Asn Asn Leu Gin Ser Ser Val Asn Gin Val Pro Ser Thr 2610 2615 2620
Ala Gly Met Thr Gin Gin Ser lie Asp Asn Tyr Asn Ala Lys Lys Arg 2625 2630 2635 2640
Glu Ala Glu Thr Glu He Thr Ala Ala Gin Arg Val He Asp Asn Gly 2645 2650 2655
Asp Ala Thr Ala Gin Gin He Ser Asp Glu Lys His Arg Val Asp Asn 2660 2665 2670
Ala Leu Thr Ala Leu Asn Gin Ala Lys His Asp Leu Thr Ala Asp Thr 2675 2680 2685
His Ala Leu Glu Gin Ala Val Gin Gin Leu Asn Arg Thr Gly Thr Thr 2690 2695 2700
Thr Gly Lys Lys Pro Ala Ser lie Thr Ala Tyr Asn Asn Ser lie Arg 2705 2710 2715 2720
Ala Leu Gin Ser Asp Leu Thr Ser Ala Lys Asn Ser Ala Asn Ala lie 2725 2730 2735 lie Gin Lys Pro lie Arg Thr Val Gin Glu Val Gin Ser Ala Leu Thr 2740 2745 2750
Asn Val Asn Arg Val Asn Glu Arg Leu Thr Gin Ala lie Asn Gin Leu 2755 2760 2765
Val Pro Leu Ala Asp Asn Ser Ala Leu Arg Thr Ala Lys Thr Lys Leu 2770 2775 2780
Asp Glu Glu lie Asn Lys Ser Val Thr Thr Asp Gly Met Thr Gin Ser 2785 2790 2795 2800
Ser lie Gin Ala Tyr Glu Asn Ala Lys Arg Ala Gly Gin Thr Glu Thr 2805 2810 2815
Thr Asn Ala Gin Asn Val lie Asn Asn Gly Asp Ala Thr Asp Gin Gin 2820 2825 2830 lie Ala Ala Glu Lys Thr Lys Val Glu Glu Lys Tyr Asn Ser Leu Lys 2835 2840 2845
Gin Ala lie Ala Gly Leu Thr Pro Asp Leu Ala Pro Leu Gin Thr Ala 2850 2855 2860
Lys Thr Gin Leu Gin Asn Asp lie Asp Gin Pro Thr Ser Thr Thr Gly 2865 2870 2875 2880
Met Thr Ser Ala Ser Val Ala Ala Phe Asn Asp Lys Leu Ser Ala Ala 2885 2890 2895
Arg Thr Lys lie Gin Glu lie Asp Arg Val Leu Ala Ser His Pro Asp 2900 2905 2910
Val Ala Thr lie Arg Gin Asn Val Thr Ala Ala Asn Ala Ala Lys Thr 2915 2920 2925
Ala Leu Asp Gin Ala Arg Asn Gly Leu Thr Val Asp Lys Ala Pro Leu 2930 2935 2940
Glu Asn Ala Lys Asn Gin Leu Gin His Ser He Asp Thr Gin Thr Ser 2945 2950 2955 2960
Thr Thr Gly Met Thr Gin Asp Ser lie Asn Ala Tyr Asn Ala Lys Leu 2965 2970 2975
Thr Ala Ala Arg Asn Lys Val Gin Gin lie Asa Gin Val Leu Ala Gly 13- 119629-序列表.doc 200815028 2980 2985 2990
Sex Pro Thr Val Asp Gin He Asn Thr Asn Thr Ser Ala Ala Asn Gin 2995 3000 3005
Ala Lys Ser Asp Leu Asp His Ala Arg Gin Ala Leu Thr Pro Asp Lys 3010 3015 3020
Ala Fro Leu Gin Asn Ala Lys Thr Gin Leu Glu Gin Ser lie Asn Gin 3025 3030 3035 3040
Pro Thr Asp Thr Thr Gly Met Thr Thr Ala Ser Leu Asn Ala Tyr Asn 3045 3050 3055
Gin Lys Leu Gin Ala Ala Arg Gin Lys Leu Thr Glu lie Asn Gin Val 3060 3065 3070
Leu Asn Gly Asn Pro Thr Val Gin Asn He Asn Asp Lys Val Ala Glu 3075 3080 3085
Ala Asn Gin Ala Lys Asp Gin Leu Asn Thr Ala Arg Gin Gly Leu Thr 3090 3095 3100
Leu Asp Arg Gin Pro Ala Leu Thr Thr Leu His Gly Ala Ser Asn Leu 3105 3110 3115 3120
Asn Gin Ala Gin Gin Asn Asn Phe Thr Gin Gin lie Asn Ala Ala Gin 3125 3130 3135
Asn His Ala Ala Leu Glu Thr He Lys Ser Asn lie Thr Ala Leu Asn 3140 3145 3150
Thr Ala Met Thr Lys Leu Lys Asp Ser Val Ala Asp Asn Asn Thr lie 3155 3160 3165
Lys Ser Gly Gin Asn Tyr Thr Asp Ala Thr Pro Ala Asn Lys Gin Ala 3170 3175 3180
Tyr Asp Asn Ala Val Asn Ala Ala Lys Gly Val lie Gly Glu Thr Thr 3185 3190 3195 3200
Asn Pro Thr Met Asp Val Asn Thr Val Asn Gin Lys Ala Ala Ser Val 3205 3210 3215
Lys Ser Thr Lys Asp Ala Leu Asp Gly Gin Gin Asn Leu Gin Arg Ala 3220 3225 3230
Lys Thr Glu Ala Thr Asn Ala He Thr His Ala Ser Asp Leu Asn Gin 3235 3240 3245
Ala Gin Lys Asn Ala Leu Thr Gin Gin Val Asn Ser Ala Gin Asn Val 3250 3255 3260
Gin Ala Val Asn Asp lie Lys Gin Thr Thr Gin Ser Leu Asn Thr Ala 3265 3270 3275 3280
Met Thr Gly Leu Lys Arg Gly Val Ala Asn His Asn Glo Val Val Gin 3285 3290 3295
Ser Asp Asn Tyr Val Asn Ala Asp Thr Asn Lys Lys Asn Asp Tyr Asn 3300 3305 3310
Asn Ala Tyr Asn His Ala Asn Asp He lie Asn Gly Asn Ala Gin His 3315 3320 3325
Pro Val lie Thr Pro Ser Asp Val Asn Asn Ala Leu Ser Asn Val Thr 3330 3335 3340
Ser Lys Glu His Ala Leu Asn Gly Glu Ala Lys Leu Asn Ala Ala Lys 3345 3350 3355 3360
Gin Glu Ala Asn Thr Ala Leu Gly His Leu Asn Asn Leu Asn Asn Val 3365 3370 3375
Gin Arg Gin Asn Leu Gin Ser Gin lie Asn Gly Ala His Gin He Asp 3380 3385 3390
Ala Val Asn Thr He Lys Gin Asn Ala Thr Asn Leu Asn Ser Ala Met 3395 3400 3405
Gly Asn Leu Arg Gin Ala Val Ala Asp Lys Asp Gin Val Lys Arg Thr 3410 3415 3420
Glu Asp Tyr Ala Asp Ala Asp Thr Ala Lys Gin Asn Ala Tyr Asn Ser 3425 3430 3435 3440
Ala Val Ser Ser Ala Glu Thr lie lie Asn Gin Thr Ala Asn Pro Thr 3445 3450 3455
Met Ser Val Asp Asp Val Asn Arg Ala Thr Ser Ala Val Thr Thr Asn 3460 3465 3470
Lys Asn Ala Leu Asn Gly Asp Glu Lys Leu Val Gin Ser Lys Thr Asp 3475 3480 3485
Ala Ala Arg Ala lie Asp Ala Leu Pro His Leu Asn Asn Ala Gin Lys 3490 3495 3500
Ala Asp Val Lys Ser Lys lie Asn Ala Ala Ser Asn He Ala Gly Val 3505 3510 3515 3520
Asn Thr Val Lys Gin Gin Gly Thr Asp Leu Asn Thr Ala Met Gly Asn 3525 3530 3535
Leu Gin Gly Ala lie Asn Asp Glu Gin Thr Thr Leu Asn Ser Gin Asn 3540 3545 3550
Tyr Gin Asp Ala Thr Pro Ser Lys Lys Thr Ala Tyr Thr Asn Ala Val 3555 3560 3565
Gin Ala Ala Lys Asp lie Leu Asn Lys Ser Asn Gly Gin Asn Lys Thr 3570 3575 3580 -14- 119629-序列表.doc 200815028
Lys Asp Gin Val Thr Glu Ala Met Asn Gin Val Asn Ser Ala Lys Asn 3585 3590 3595 3600
Asn Leu Asp Gly Thr Arg Leu Leu Asp Gin Ala Lys Gin Thr Ala Lys 3605 3610 3615
Gin Gin Leu Asn Asn Met Thr His Leu Thr Thr Ala Gin Lys Thr Asn 3620 3625 3630
Leu Thr Asn Gin lie Asn Ser Gly Thr Thr Val Ala Gly Val His Thr 3635 3640 3645
Val Gin Ser Asn Ala Asn Thr Leu Asp Gin Ala Met Asn Thr Leu Arg 3650 3655 3660
Gin Ser lie Ala Asn Asn Asp Ala Thr Lys Ala Ser Glu Asp Tyr Val 3665 3670 3675 3680
Asp Ala Asn Asn Asp Lys Gin Thr Ala Tyr Asn Asn Ala Val Ala Ala 3685 3690 . 3695
Ala Glu Thr lie lie Asn Ala Asn Ser Asn Pro Glu Met Asn Pro Ser 3700 3705 3710
Thr He Thr Gin Lys Ala Glu Gin Val Asn Ser Ser Lys Thr Ala Leu 3715 3720 3725
Asn Gly Asp Glu Asn Leu Ala Thr Ala Lys Gin Asn Ala Lys Thr Tyr 3730 3735 3740
Leu Asn Thr Leu Thr Ser lie Thr Asp Ala Gin Lys Asn Asn Leu He 3745 3750 3755 3760
Ser Gin lie Ser Ser Ala Thr Arg Val Ser Gly Val Asp Thr Val Lys 3765 3770 3775
Gin Asn Ala Gin His Leu Asp Gin Ala Met Ala Asn Leu Gin Asn Gly 3780 3785 3790
He Asn Asn Glu Ser Gin Val Lys Ser Ser Glu Lys Tyr Arg Asp Ala 3795 3800 3805
Asp Thr Asn Lys Gin Gin Glu Tyr Asp Asn Ala lie Thr Ala Ala Lys 3810 3815 3820
Ala lie Leu Asn Lys Ser Thr Gly Pro Asn Thr Ala Gin Asn Ala Val 3825 3830 3835 3840
Glu Ala Ala Leu Gin Arg Val Asn Thr Ala Lys Asp Ala Leu Asn Gly 3845 3850 3855
Asp Ala Lys Leu lie Ala Ala Gin Asn Ala Ala Lys Gin His Leu Gly 3860 3865 3870
Thr Leu Thr His He Thr Thr Ala Gin Arg Asn Asp Leu Thr Asn Gin 3875 3880 3885 lie Ser 3890 <210> 13 <211〉 6713 <212〉 PRT <213〉葡萄球菌 <400> 13
Met Gly Asn Leu Gin Thr Ala He Asn Asp Lys Ser Gly Thr Leu Ala 1 5 10 15
Ser Gin Asn Phe Leu Asp Ala Asp Glu Gin Lys Arg Asn Ala Tyr Asn 20 25 30
Gin Ala He Ser Ala Ala Glu Thr He Leu Asn Lys Gin Thr Gly Pro 35 40 45
Asn Thr Ala Lys Thr Ala Val Glu Gin Ala Leu Asn Asn Val Asn Ser 50 55 60
Ala Lys His Ala Leu Asn Gly Thr Gin Asn Leu Asn Asn Ala Lys Gin 65 70 75 80
Ala Ala lie Thr Ala lie Asn Gly Ala Ser Asp Leu Asn Gin Lys Gin 85 90 95
Lys Asp Ala Leu Lys Ala Gin Ala Asn Gly Ala Gin Arg Val Ser Asn 100 105 110
Ala Asn Asp Val Gin Arg Asn Ala Thr Glu Leu Asn Thr Ala Met Gly 115 120 125
Gin Leu Gin His Ala lie Ala Asp Lys Thr Asn Thr Leu Ala Ser Ser 130 135 140
Lys Tyr Val Asn Ala Asp Ser Thr Lys Gin Asn Ala Tyr Thr Thr Lys 145 150 155 160
Val Thr Asn Ala Glu His He lie Ser Gly Thr Pro Thr Val Val Thr 165 170 175
Thr Pro Ser Glu Val Thr Ala Ala Ala Asn Gin Val Asn Ser Ala Lys 180 185 190
Gin Glu Leu Asn Gly Asp Glu Arg Leu Arg Val Ala Lys Gin Asn Ala 195 200 205
Asn Thr Ala lie Asp Ala Leu Thr Gin Leu Asn Thr Pro Gin Lys Ala 15- 119629-序列表.doc 200815028 210 215 220
Lys Leu Lys Glu Gin Val Gly Gin Ala Asn Arg Leu Glu Asp Val Gin 225 230 235 240
Ser Val Gin Thr Asn Gly Gin Ser Leu Asn Asn Ala Met Lys Gly Leu 245 250 255
Arg Asp Ser He Ala Asn Glu Thr Thr Val Lys Ala Ser Gin Asn Tyr 260 265 270
Thr Asp Ala Ser Pro Asn Asn Gin Ser Thr Tyr Asn Ser Ala Val Ser 275 280 285
Asn Ala Lys Gly lie He Asn Gin Thr Asn Asn Pro Thr Met Asp Thr 290 295 300
Ser Ala lie Thr Gin Ala Thr Thr Gin Val Asn Asn Ala Lys Asn Gly 305 310 315 320
Leu Asn Gly Ala Glu Asn Leu Arg Asn Ala Gin Asn Thr Ala Lys Gin 325 330 335
Asn Leu Asn Thr Leu Ser His Leu Thr Asn Asn Gin Lys Ser Ala lie 340 345 350
Ser Ser Gin lie Asp Arg Ala Gly His Val Ser Glu Val Thr Ala Ala 355 360 365
Lys Asn Ala Ala Thr Glu Leu Asn Ala Gin Met Gly Asn Leu Glu Gin 370 375 380
Ala lie His Asp Gin Asn Thr Val Lys Gin Gly Val Asn Phe Thr Asp 385 390 395 400
Ala Asp Lys Ala Lys Arg Asp Ala Tyr Thr Asn Ala Val Ser Arg Ala 405 410 415
Glu Thr lie Leu Asn Lys Thr Gin Gly Ala Asn Thr Ser Lys Gin Asp 420 425 430
Val Glu Ala Ala lie Gin Asn Val Thr Ser Ala Lys Asn Ala Leu Asn 435 440 445
Gly Asp Gin Asn Val Thr Asn Ala Lys Asn Ala Ala Lys Asn Ala Leu 450 455 460
Asn Asn Leu Thr Ser lie Asn Asn Ala Gin Lys Arg Asp Leu Thr Thr 465 470 475 480
Lys lie Asp Gin Ala Thr Thr Val Ala Gly Val Glu Ala Val Ser Asn 485 490 495
Thr Gly Thr Gin Leu Asn Thr Ala Met Ala Asn Leu Gin Asn Gly lie 500 505 510
Asn Asp Lys Ala Asn Thr Leu Ala Ser Glu Asn Tyr His Asp Ala Asp 515 520 525
Ser Asp Lys Lys Thr Ala Tyr Thr Gin Ala Val Thr Asn Ala Glu Asn 530 535 540 lie Leu Asn Lys Asn Ser Gly Ser Asn Leu Asp Lys Ala Ala Val Glu 545 550 555 560
Asn Ala Leu Ser Gin Val Thr Asn Ala Lys Gly Ala Leu Asn Gly Asn 565 570 575
His Asn Leu Glu Gin Ala Lys Ser Asn Ala Asn Thr Thr lie Asn Gly 580 585 590
Leu Gin His Leu Thr Thr Ala Gin Lys Asp Lys Leu Lys Gin Gin Val 595 600 605
Gin Gin Ala Gin Asn Val Ala Gly Val Asp Thr Val Lys Ser Ser Ala 610 615 620
Asn Thr Leu Asn Gly Ala Met Gly Thr Leu Arg Asn Ser lie Gin Asp 625 630 635 640
Asn Thr Ala Thr Lys Asn Gly Gin Asn Tyr Leu Asp Ala Thr Glu Arg 645 650 655
Asn Lys Thr Asn Tyr Asn Asn Ala Val Asp Ser Ala Asn Gly Val lie 660 665 670
Asn Ala Thr Ser Asn Pro Asn Met Asp Ala Asn Ala He Asn Gin lie 675 680 685
Ala Thr Gin Val Thr Ser Thr Lys Asn Ala Leu Asp Gly Thr His Asn 690 695 700
Leu Thr Gin Ala Lys Gin Thr Ala Thr Asn Ala lie Asp Gly Ala Thr 705 710 715 720
Asn Leu Asn Lys Ala Gin Lys Asp Ala Leu Lys Ala Gin Val Thr Ser 725 730 735
Ala Gin Arg Val Ala Asn Val Thr Ser lie Gin Gin Thr Ala Asn Glu 740 745 750
Leu Asn Thr Ala Met Gly Gin Leu Gin His Gly lie Asp Asp Glu Asn 755 760 765
Ala Thr Lys Gin Thr Gin Lys Tyr Arg Asp Ala Glu Gin Ser Lys Lys 770 775 780
Thr Ala Tyr Asp Gin Ala Val Ala Ala Ala Lys Ala lie Leu Asn Lys 785 790 795 800
Gin Thr Gly Ser Asn Ser Asp Lys Ala Ala Val Asp Arg Ala Leu Gin 805 810 815 -16· 119629-序列表.doc 200815028
Gin Val Thr Ser Thr Lys Asp Ala Leu Asn Gly Asp Ala Lys Leu Ala 820 825 830
Glu Ala Lys Ala Ala Ala Arg Gin Asn Leu Gly Thr Leu Asn His He 835 840 845
Thr Asn Ala Gin Arg Thr Ala Leu Glu Gly Gin lie Asn Gin Ala Thr 850 855 860
Thr Val Asp Gly Val Asn Thr Val Lys Thr Asn Ala Asn Thr Leu Asp 865 870 875 880
Gly Ala Met Asn Ser Leu Gin Gly Ala He Asn Asp Lys Asp Ala Thr 885 890 895
Leu Arg Asn Gin Asn Tyr Leu Asp Ala Asp Glu Ser Lys Arg Asn Ala 900 905 910
Tyr Thr Gin Ala Val Thr Ala Ala Glu Gly lie Leu Asn Lys Gin Thr 915 920 925
Gly Gly Asn Thr Ser Lys Ala Asp Val Asp Asn Ala Leu Asn Ala Val 930 935 940
Thr Arg Ala Lys Ala Ala Leu Asn Gly Ala Glu Asn Leu Arg Asn Ala 945 950 955 960
Lys Thr Ser Ala Thr Asn Thr lie Asn Gly Leu Pro Asn Leu Thr Gin 965 970 975
Leu Gin Lys Asp Asn Leu Lys His Gin Val Glu Gin Ala Gin Asn Val 980 985 990
Val Gly Val Asn Gly Val Lys Asp Lys Gly Asn Thr Leu Asn Thr Ala 995 1000 1005
Met Gly Ala Leu Arg Thr Ser He Gin Asn Asp Asn Thr Thr Lys Thr 1010 1015 1020
Ser Gin Asn Tyr Leu Asp Ala Ser Asp Ser Asn Lys Asn Asn Tyr Asn 1025 1030 1035 1040
Thr Ala Val Asn Asn Ala Asn Gly Val lie Asn Ala Thr Asn Asn Pro 1045 1050 1055
Asn Met Asp Ala Asn Ala He Asn Asp Met Ala Asn Gin Val Asn Thr 1060 1065 1070
Thr Lys Ala Ala Leu Asn Gly Ala Gin Asn Leu Ala Gin Ala Lys Thr 1075 1080 1085
Asn Ala Thr Asn Thr lie Asn Asn Ala Gin Asp Leu Asn Gin Lys Gin 1090 1095 1100
Lys Asp Ala Leu Lys Thr Gin Val Asn Asn Ala Gin Arg Val Ser Asp 1105 1110 1115 1120
Ala Asn Asn Val Gin His Thr Ala Thr Glu Leu Asn Gly Ala Met Thr 1125 1130 1135
Ala Leu Lys Ala Ala lie Ala Asp Lys Glu Arg Thr Lys Ala Ser Gly 1140 1145 1150
Asn Tyr Val Asn Ala Asp Gin Glu Lys Arg Gin Ala Tyr Asp Ser Lys 1155 1160 1165
Val Thr Asn Ala Glu Asn lie lie Asn Gly Thr Pro Asn Ala Thr Leu 1170 1175 1180
Thr Val Asn Asp Val Asn Ser Ala Ala Ser Gin Val Asn Ala Ala Lys 1185 1190 1195 1200
Thr Ala Leu Asn Gly Asp Asn Asn Leu Arg Val Ala Lys Glu His Ala 1205 1210 1215
Asn Asn Thr lie Asp Gly Leu Ala Gin Leu Asn Asn Val Gin Lys Ala 1220 1225 1230
Lys Leu Lys Glu Gin Val Gin Ser Ala Thr Thr Leu Asp Gly Val Gin 1235 1240 1245
Thr Val Lys Asn Ser Ser Gin Thr Leu Asn Thr Ala Met Lys Gly Leu 1250 1255 1260
Arg Asp Ser lie Ala Asn Glu Ala Thr lie Lys Ala Gly Gin Asn Tyr 1265 1270 1275 1280
Thr Asp Ala Ser Pro Asn Asn Arg Aso Glu Tyr Asp Ser Ala Val Thr 1285 1290 1295
Ala Ala Lys Ala lie lie Asn Gin Thr Ser Asn Pro Thr Met Glu Pro 1300 1305 1310
Asn Thr lie Thr Gin Ala Thr Ser Gin Val Thr Thr Lys Glu His Ala 1315 1320 1325
Leu Asn Gly Ala Gin Asn Leu Ala Gin Ala Lys Thr Thr Ala Lys Asn 1330 1335 1340
Asn Leu Asn Asn Leu Thr Ser lie Asn Asn Ala Gin Lys Asp Ala Leu 1345 1350 1355 1360
Thr Arg Asn lie Asp Gly Ala Thr Thr Val Ala Gly Val Asn Gin Glu 1365 1370 1375
Thr Ala Lys Ala Thr Glu Leu Asn Asn Ala Met His Ser Leu Gin Asn 1380 1385 1390
Gly lie Asn Asp Glu Thr Gin Thr Lys Gin Thr Gin Lys Tyr Leu Asp 1395 1400 1405
Ala Glu Pro Ser Lys Lys Ser Ala Tyx Asp Gin Ala Val Asn Ala Ala 17- 119629-序列表.doc 200815028 1410 1415 1420
Lys Ala lie Leu Thr Lys Ala Ser Gly Gin Asn Val Asp Lys Ala Ala 1425 1430 1435 1440
Val Glu Gin Ala Leu Gin Asn Val Asn Ser Thr Lys Thr Ala Leu Asn 1445 1450 1455
Gly Asp Ala Lys Leu Asn Glu Ala Lys Ala Ala Ala Lys Gin Thr Leu 1460 1465 1470
Gly Thr Leu Thr His lie Asn Asn Ala Gin Arg Asn Ala Leu Asp Asn 1475 1480 1485
Glu lie Thr Gin Ala Thr Asn Val Glu Gly Val Asn Thr Val Lys Ala 1490 1495 1500
Lys Ala Gin Gin Leu Asp Gly Ala Met Gly Gin Leu Glu Thr Ser He 1505 1510 1515 1520
Arg Asp Lys Asp Thr Thr Leu Gin Ser Gin Asn Tyr Gin Asp Ala Asp 1525 1530 1535
Asp Ala Lys Arg Thr Ala Tyr Ser Gin Ala Val Asn Ala Ala Ala Thr 1540 1545 1550 lie Leu Asn Lys Thr Ala Gly Gly Asn Thr Pro Lys Ala Asp Val Glu 1555 1560 1565
Arg Ala Met Gin Ala Val Thr Gin Ala Asn Thr Ala Leu Asn Gly lie 1570 1575 1580
Gin Asn Leu Glu Arg Ala Lys Gin Ala Ala Asn Thr Ala lie Thr Asn 1585 1590 1595 1600
Ala Ser Asp Leu Asn Thr Lys Gin Lys Glu Ala Leu Lys Ala Gin Val 1605 1610 1615
Thr Ser Ala Gly Arg Val Ser Ala Ala Asn Gly Val Glu His Thr Ala 1620 1625 1630
Thr Glu Leu Asn Thr Ala Met Thr Ala Leu Lys Arg Ala lie Ala Asp 1635 1640 1645
Lys Ala Asp Thr Lys Ala Ser Gly Asn Tyr Val Asn Ala Asp Ala Asn 1650 1655 1660
Lys Arg Gin Ala Tyr Asp Glu Lys Val Thr Ala Ala Glu His He Val 1665 1670 1675 1680
Ser Gly Thr Pro Thr Pro Thr Leu Thr Pro Ser Asp Val Thr Asn Ala 1685 1690 1695
Ala Thr Gin Val Thr Asn Ala Lys Thr Gin Leu Asn Gly Asn His Asn 1700 1705 1710
Leu Glu Val Ala Lys Gin Asn Ala Asn Thr Ala lie Asp Gly Leu Thr 1715 1720 1725
Ser Leu Asn Gly Pro Gin Lys Ala Lys Leu Lys Glu Gin Val Gly Gin 1730 1735 1740
Ala Thr Thr Leu Pro Asn Val Gin Thr Val Arg Asp Asn Ala Gin Thr 1745 1750 1755 1760
Leu Asn Thr Ala Met Lys Gly Leu Arg Asp Ser He Ala Asn Glu Ala 1765 1770 1775
Thr lie Lys Ala Gly Gin Asn Tyr Thr Asp Ala Ser Gin Asn Lys Gin 1780 1785 1790
Asn Asp Tyr Asn Asn Ala Val Thr Ala Ala Lys Ala lie lie Gly Gin 1795 1800 1805
Thr Thr Ser Pro Ser Met lie Ala Gin Glu lie Asn Gin Ala Lys Asp 1810 1815 1820
Gin Val Thr Ala Lys Gin Gin Ala Leu Asn Gly Gin Glu Asn Leu Arg 1825 1830 1835 1840
Thr Ala Gin Thr Asn Ala Lys Gin His Leu Asn Gly Leu Ser Asp Leu 1845 1850 1855
Thr Asn Ala Gin Lys Asp Ala Ala Lys Arg Gin lie Glu Gly Ala Thr 1860 1865 1870
His Val Asn Glu Val Thr Gin Ala Gin Asn Asn Ala Asp Ala Leu Asn 1875 1880 1885
Thr Ala Met Thr Asn Leu Lys Asn Gly lie Gin Asp Gin Asn Thr lie 1890 1895 1900
Lys Gin Gly Val Asn Phe Thr Asp Ala Asp Glu Ala Lys Arg Asn Ala 1905 1910 1915 1920
Tyr Thr Asn Ala Val Thr Gin Ala Glu Gin lie Leu Asn Lys Ala Gin 1925 1930 1935
Gly Pro Asn Thr Ala Lys Asp Gly Val Glu Thr Ala Leu Gin Asn Val 1940 1945 1950
Gin Arg Ala Lys Asn Glu Leu Asn Gly Asn Gin Asn Val Ala Asn Ala 1955 1960 1965
Lys Thr Thr Ala Lys Asn Ala Leu Asn Asn Leu Thr Ser lie Asn Asn 1970 1975 1980
Ala Gin Lys Ala Ala Leu Lys Ser Gin lie Glu Gly Ala Thr Thr Val 1985 1990 1995 2000
Ala Gly Val Asn Gin Val Ser Thr Met Ala Ser Glu Leu Asn Thr Ala 18- 119629-序列表.doc 200815028 2005 2010 2015
Met Ser Asn Leu Gin Arg Gly lie Asn Asp Glu Ala Ala Thr Lys Ala 2020 2025 2030
Ala Gin Lys Tyr Thr Glu Ala Asp Arg Asp Lys Gin Thr Ala Tyr Asn 2035 2040 2045
Asp Ala Val Thr Ala Ala Lys Thr Leu Leu Asp Lys Thr Ala Gly Ser 2050 2055 2060
Asn Asp Asn Lys Val Ala Val Glu Gin Ala Leu Gin Arg Val Asn Thr 2065 2070 2075 2080
Ala Lys Thr Ala Leu Asn Gly Asp Ala Arg Leu Asn Glu Ala Lys Asn 2085 2090 2095
Thr Ala Lys Gin Gin Leu Ala Thr Met Ser His Leu Thr Asn Ala Gin 2100 2105 2110
Lys Ala Asn Leu Thr Glu Gin lie Glu Arg Gly Thr Thr Val Ala Gly 2115 2120 2125
Val Gin Gly lie Gin Ala Asn Ala Gly Thr Leu Asn Gin Ala Met Asn 2130 2135 2140
Gin Leu Arg Gin Ser He Ala Ser Lys Asp Ala Thr Lys Ser Ser Glu 2145 2150 2155 2160
Asp Tyr Gin Asp Ala Asn Ala Asp Leu Gin Asn Ala Tyr Asn Asp Ala 2165 2170 2175
Val Thr Asn Ala Glu Gly lie He Ser Ala Thr Asn Asn Pro Glu Met 2180 2185 2190
Asn Pro Asp Thr lie Asn Gin Lys Ala Ser Gin Val Asn Ser Ala Lys 2195 2200 2205
Ser Ala Leu Asn Gly Asp Glu Lys Leu Ala Ala Val Lys Gin Thr Ala 2210 2215 2220
Lys Ser Asp He Gly Arg Leu Thr Asp Leu Asn Asn Ala Gin Arg Thr 2225 2230 2235 2240
Ala Ala Asn Ala Glu Val Asp Gin Ala Pro Asn Leu Ala Ala Val Thr 2245 2250 2255
Ala Ala Lys Asn Lys Ala Thr Ser Leu Asn Thr Ala Met Gly Asn Leu 2260 2265 2270
Lys His Ala Leu Ala Glu Lys Asp Asn Thr Lys Arg Ser Val Asn Tyr 2275 2280 2285
Thr Asp Ala Asp Gin Pro Lys Gin Gin Ala Tyr Asp Thr Ala Val Thr 2290 2295 2300
Gin Ala Glu Ala He Thr Asn Ala Asn Gly Ser Asn Ala Asn Glu Thr 2305 2310 2315 2320
Gin Val Gin Ala Ala Leu Asn Gin Leu Asn Gin Ala Lys Asn Asp Leu 2325 2330 2335
Asn Gly Asp Asn Lys Val Ala Gin Ala Lys Glu Thr Ala Lys Arg Ala 2340 2345 2350
Leu Ala Ser Tyr Ser Asn Leu Asn Asn Ala Gin Ser Thr Ala Ala Thr 2355 2360 2365
Ser Gin lie Asp Asn Ala Thr Thr Val Ala Asp Val Thr Ala Ala Gin 2370 2375 2380
Asn Thr Ala Asn Glu Leu Asn Thr Ala Met Gly Gin Leu Gin Asn Gly 2385 2390 2395 2400 lie Asn Asp Gin Asn Thr Val Lys Gin Gin Val Asn Phe Thr Asp Ala 2405 2410 2415
Asp Gin Gly Lys Lys Asp Ala Tyr Thr Asn Ala Val Thr Asn Ala Gin 2420 2425 2430
Gly lie Leu Asp Lys Ala Asn Gly Gin Asn Met Thr Lys Ala Gin Val 2435 2440 2445
Glu Ala Ala Leu Asn Gin Val Thr Thr Ala Lys Asn Ala Leu Asn Gly 2450 2455 2460
Asp Ala Asn Val Arg Gin Ala Lys Ser Asp Ala Lys Ala Asn Leu Gly 2465 2470 2475 2480
Thr Leu Thr His Leu Asn Asn Ala Gin Lys Gin Asp Leu Thr Ser Gin 2485 2490 2495 lie Glu Gly Ala Thr Thr Val Asn Gly Val Asn Ser Val Lys Thr Lys 2500 2505 2510
Ala Gin Asp Leu Asp Gly Ala Met Gin Arg Leu Glu Ser Ala lie Ala 2515 2520 2525
Asn Lys Asp Gin Thr Lys Ala Ser Glu Asn Tyr lie Asp Ala Asp Pro 2530 2535 2540
Thr Lys Lys Thr Ala Phe Asp Asn Ala lie Thr Gin Ala Glu Ser Tyr 2545 2550 2555 2560
Leu Asn Lys Asp His Gly Thr Asn Lys Asp Lys Gin Ala Val Glu Gin 2565 2570 2575
Ala lie Gin Ser Val Thr Ser Thr Glu Asn Ala Leu Asn Gly Asp Ala 2580 2585 2590
Asn Leu Gin Cys Ala Lys Thr Glu Ala Thr Gin Ala lie Asp Asn Leu 19- U 9629·序列表.doc 200815028 2595 2600 2605
Thr Gin Leu Asn Thr Pro Gin Lys Thr Ala Leu Lys Gin Gin Val Asn 2610 2615 2620
Ala Ala Gin Arg Val Ser Gly Val Thr Asp Leu Lys Asn Ser Ala Thr 2625 2630 2635 2640
Ser Leu Asn Asn Ala Met Asp Gin Leu Lys Gin Ala lie Gly Asp His 2645 2650 2655
Asp Thr lie Val Ala Gly Gly Asn Tyr Thr Asn Ala Ser Pro Asp Lys 2660 2665 2670
Gin Gly Ala Tyr Thr Asp Ala Tyr Asn Ala Ala Lys Asn lie Val Asn 2675 2680 2685
Gly Ser Pro Asn Val lie Thr Asn Ala Ala Asp Val Thr Ala Ala Thr 2690 2695 2700
Gin Arg Val Asn Asn Ala Glu Thr Ser Leu Asn Gly Asp Thr Asn Leu 2705 2710 2715 2720
Ala Thr Ala Lys Gin Gin Ala Lys Asp Ala Leu Arg Gin Met Thr His 2725 2730 2735
Leu Ser Asp Ala Gin Lys Gin Ser He Thr Gly Gin lie Asp Ser Ala 2740 2745 2750
Thr Gin Val Thr Gly Val Gin Ser Val Lys Asp Asn Ala Thr Asn Leu 2755 2760 2765
Asp Asn Ala Met Asn Gin Leu Arg Asn Ser lie Ala Asn Lys Asp Glu 2770 2775 2780
Val Lys Ala Ser Gin Pro Tyr Val Asp Ala Asp Thr Asp Lys Gin Asn 2785 2790 2795 2800
Ala Tyr Asn Thr Ala Val Thr Ser Ala Glu Asn lie He Asn Ala Thr 2805 2810 2815
Ser Gin Pro Thr Leu Asp Pro Ser Ala Val Thr Gin Ala Ala Asn Gin 2820 2825 2830
Val Asn Thr Asn Lys Thr Ala Leu Asn Gly Ala Gin Asn Leu Ala Asn 2835 2840 2845
Lys Lys Gin Glu Thr Thr Ala Asn lie Asn Arg Leu Ser His Leu Asn 2850 2855 2860
Asn Ala Gin Lys Gin Asp Leu Asn Thr Gin Val Thr Asn Ala Pro Asn 2865 2870 2875 2880 lie Ser Thr Val Asn Gin Val Lys Thr Lys Ala Glu Gin Leu Asp Gin 2885 2890 2895
Ala Wet Glu Arg Leu lie Asn Gly lie Gin Asp Lys Asp Gin Val Lys 2900 2905 2910
Gin Ser Val Asn Phe Thr Asp Ala Asp Pro Giu Lys Gin Thr Ala Tyr 2915 2920 2925
Asn Asn Ala Val Thr Ala Ala Glu Asn lie lie Asn Gin Ala Asn Gly 2930 2935 2940
Thr Asn Ala Asn Gin Ser Gin Val Glu Ala Ala Leu Ser Thr Val Thr 2945 2950 2955 2960
Thr Thr Lys Gin Ala Leu Asn Gly Asp Arg Lys Val Thr Asp Ala Lys 2965 2970 2975
Asn Asn Ala Asn Gin Thr Leu Ser Thr Leu Asp Asn Leu Asn Asn Ala 2980 2985 2990
Gin Lys Gly Ala Val Thr Gly Asn lie Asn Gin Ala His Thr Val Ala 2995 3000 3005
Glu Val Thr Gin Ala lie Gin Thr Ala Gin Glu Leu Asn Thr Ala Met 3010 3015 3020
Gly Asn Leu Lys Asn Ser Leu Asn Asp Lys Asp Thr Thr Leu Gly Ser 3025 3030 3035 3040
Gin Asn Phe Ala Asp Ala Asp Pro Glu Lys Lys Asn Ala Tyr Asn Glu 3045 3050 3055
Ala Val Arg Asn Ala Glu Asn lie Leu Asn Lys Ser Thr Gly Thr Asn 3060 3065 3070
Val Pro Lys Asp Gin Val Glu Ala Ala Met Asn Gin Val Asn Thr Thr 3075 3080 3085
Lys Ala Ala Leu Asn Gly Thr Gin Asn Leu Glu Lys Ala Lys Gin His 3090 3095 3100
Ala Asn Thr Ala lie Asp Gly Leu Ser His Leu Thr Asn Ala Gin Lys 3105 3110 3115 3120
Glu Ala Leu Lys Gin Leu Val Gin Gin Ser Thr Thr Val Ala Glu Ala 3125 3130 3135
Gin Gly Asn Glu Gin Lys Ala Asn Asn Val Asp Ala Ala Met Asp Lys 3140 3145 3150
Leu Arg Gin Ser lie Ala Asp Asn Ala Thr Thr Lys Gin Asn Gin Asn 3155 3160 3165
Tyr Thr Asp Ala Ser Pro Asn Lys Lys Asp Ala Tyr Asn Asn Ala Val 3170 3175 3180
Thr Thr Ala Gin Gly lie lie Asp Gin Thr Thr Asn Pro Ser Leu Asp 3185 3190 3195 3200 20 119629-序列表.doc 200815028
Pro Thr Val lie Asn Gin Ala Ala Gly Gin Val Ser Thr Ser Lys Asn 3205 3210 3215
Ala Leu Asn Gly Asn Glu Asn Leu Glu Ala Ala Lys Gin Gin Ala Thr 3220 3225 3230
Gin Ser Leu Gly Ser Leu Asp Asn Leu Asn Asn Ala Gin Lys Gin Ala 3235 3240 3245
Val Thr Asn Gin lie Asn Gly Ala His Thr Val Asp Glu Ala Asn Gin 3250 3255 3260 lie Lys Gin Asn Ala Gin Asn Leu Asn Thr Ala Met Gly Asn Leu Lys 3265 3270 3275 3280
Gin Ala lie Ala Asp Lys Asp Ala Thr Lys Ala Thr Val Asn Phe Thr 3285 3290 3295
Asp Ala Asp Gin Ala Lys Gin Gin Ala Tyr Asn Thr Ala Val Thr Asn 3300 3305 3310
Ala Glu Asn lie lie Ser Lys Ala Asn Gly Gly Asn Ala Thr Gin Thr 3315 3320 3325
Glu Val Glu Gin Ala lie Gin Gin Val Asn Ala Ala Lys Gin Ala Leu 3330 3335 3340
Asn Gly Asn Ala Asn Val Gin His Ala Lys Asp Glu Ala Thr Ala Leu 3345 3350 3355 3360 lie Asn Asn Ser Asn Asp Leu Asn Gin Ala Gin Lys Asp Ala Leu Lys 3365 3370 3375
Gin Gin Val Gin Asn Ala Thr Thr Val Ala Gly Val Asn Asn Val Lys 3380 3385 3390
Gin Thr Ala Gin Glu Leu Asn Asn Ala Met Thr Gin Leu Lys Gin Gly 3395 3400 3405
lie Ala Asp Lys Glu Gin Thr Lys Ala Asp Gly Asn Phe Val Asn Ala 3410 3415 3420
Asp Ser Asp Lys Gin Asn Ala Tyr Asn Gin Ala Val Ala Lys Ala Glu 3425 3430 3435 3440
Ala Leu lie Ser Gly Thr Pro Asp Val Val Val Thr Pro Ser Glu He 3445 3450 3455
Thr Ala Ala Leu Asn Lys Val Thr Gin Ala Lys Asn Asp Leu Asn Gly 3460 3465 3470
Asn Thr Asn Leu Ala Thr Ala Lys Gin Asn Val Gin His Ala He Asp 3475 3480 3485
Gin Leu Pro Asn Leu Asn Gin Ala Gin Arg Asp Glu Tyr Ser Lys Gin 3490 3495 3500 lie Thr Gin Ala Thr Leu Val Pro Asn Val Asn Ala He Gin Gin Ala 3505 3510 3515 3520
Ala Thr Thr Leu Asn Asp Ala Met Thr Gin Leu Lys Gin Gly lie Ala 3525 3530 3535
Asn Lys Ala Gin lie Lys Gly Ser Glu Asn Tyr His Asp Ala Asp Thr 3540 3545 3550
Asp Lys Gin Thr Ala Tyr Asp Asn Ala Val Thr Lys Ala Glu Glu Leu 3555 3560 3565
Leu Lys Gin Thr Thr Asn Pro Thr Met Asp Pro Asn Thr lie Gin Gin 3570 3575 3580
Ala Leu Thr Lys Val Asn Asp Thr Asn Gin Ala Leu Asn Gly Asn Gin 3585 3590 3595 3600
Lys Leu Ala Asp Ala Lys Gin Asp Ala Lys Thr Thr Leu Gly Thr Leu 3605 3610 3615
Asp His Leu Asn Asp Ala Gin Lys Gin Ala Leu Thr Thr Gin Val Glu 3620 3625 3630
Gin Ala Pro Asp lie Ala Thr Val Asn Asn Val Lys Gin Asn Ala Gin 3635 3640 3645
Asn Leu Asn Asn Ala Met Thr Asn Leu Asn Asn Ala Leu Gin Asp Lys 3650 3655 3660
Thr Glu Thr Leu Asn Ser lie Asn Phe Thr Asp Ala Asp Gin Ala Lys 3665 3670 3675 3680
Lys Asp Asp Tyr Thr Asn Ala Val Ser His Ala Glu Gly lie Leu Ser 3685 3690 3695
Lys Ala Asn Gly Ser Asn Ala Ser Gin Thr Glu Val Glu Gin Ala Met 3700 3705 3710
Gin Arg Val Asn Glu Ala Lys Gin Ala Leu Asn Gly Asn Asp Asn Val 3715 3720 3725
Gin Arg Ala Lys Asp Ala Ala Lys Gin Val He Thr Asn Ala Asn Asp 3730 3735 3740
Leu Asn Gin Ala Gin Lys Asp Ala Leu Lys Gin Gin Val Asp Ala Ala 3745 3750 3755 3760
Gin Thr Val Ala Asn Val Asn Thr He Lys Gin Thr Ala Gin Asp Leu 3765 3770 3775
Asn Gin Ala Met Thr Gin Leu Lys Gin Gly lie Ala Asp Lys Asp Gin 3780 3785 3790
Thr Lys Ala Asn Gly Asn Phe Val Asn Ala Asp Thr Asp Lys Gin Asn -21 - 119629-序列表.doc 200815028 3795 3800 3805
Ala Tyr Asn Asn Ala Val Ala His Ala Glu Gin lie lie Ser Gly Thr 3810 3815 3820
Pro Asn Ala Asn Val Asp Pro Gin Gin Val Ala Gin Ala Leu Gin Gin 3825 3830 3835 3840
Val Asn Gin Ala Lys Gly Asp Leu Asn Gly Asn His Asn Leu Gin ¥al 3845 3850 3855
Ala Lys Asp Asn Ala Asn Thr Ala lie Asp Gin Leu Pro Asn Leu Asn 3860 3865 3870
Gin Pro Gin Lys Thr Ala Leu Lys Asp Gin Val Ser His Ala Glu Leu 3875 3880 3885
Val Thr Gly Val Asn Ala lie Lys Gin Asn Ala Asp Ala Leu Asn Asn 3890 3895 3900
Ala Met Gly Thr Leu Lys Gin Gin lie Gin Ala Asn Ser Gin Val Pro 3905 3910 3915 3920
Gin Ser Val Asp Phe Thr Gin Ala Asp Gin Asp Lys Gin Gin Ala Tyr 3925 3930 3935
Asn Asn Ala Ala Asn Gin Ala Gin Gin lie Ala Asn Gly Thr Pro Thr 3940 3945 3950
Pro Val Leu Ala Pro Asp Thr Val Thr Lys Ala Val Thr Thr Met Asn 3955 3960 3965
Gin Ala Lys Asp Ala Leu Asn Gly Asp Glu Lys Leu Ala Gin Ala Lys 3970 3975 3980
Gin Asp Ala Leu Ala Asn Leu Asp Thr Leu Arg Asp Leu Asn Gin Pro 3985 3990 3995 4000
Gin Arg Asp Ala Leu Arg Asn Gin lie Asn Gin Ala Gin Ala Leu Ala 4005 4010 4015
Thr Val Glu Gin Thr Lys Gin Asn Ala Gin Asn Val Asn Thr Ala Met 4020 4025 4030
Gly Asn Leu Lys Gin Gly lie Ala Asn Lys Asp Thr Val Lys Ala Ser 4035 4040 4045
Glu Asn Tyr His Asp Ala Asp Val Asp Lys Gin Thr Ala Tyr Thr Asn 4050 4055 4060
Ala Val Ser Gin Ala Glu Gly lie He Asn Gin Thr Thr Asn Pro Thr 4065 4070 4075 4080
Leu Asn Pro Asp Asp lie Thr Arg Ala Leu Thr Gin Vai Thr Asp Ala 4085 4090 4095
Lys Asn Ser Leu Asn Gly Glu Ala Lys Leu Ala Thr Glu Lys Gin Asn 4100 4105 4110
Ala Lys Asp Ala Val Ser Gly Met Thr His Leu Asn Asp Ala Gin Lys 4115 4120 4125
Gin Ala Leu Lys Gly Gin lie Asp Gin Ser Pro Glu lie Ala Thr Val 4130 4135 4140
Asn Gin Val Lys Gin Thr Ala Thr Ser Leu Asp Gin Ala Met Asp Gin 4145 4150 4155 4160
Leu Ser Gin Ala lie Asn Asp Lys Asp Gin lie Leu Ala Asp Gly Asn 4165 4170 4175
Tyr Leu Asn Ala Asp Pro Asp Lys Gin Asn Ala Tyr Lys Gin Ala Val 4180 4185 4190
Ala Lys Ala Glu Ala Leu Leu Asn Lys Gin Ser Gly Thr Asn Glu Val 4195 4200 4205
Gin Ala Gin Val Glu Ser lie Thr Asn Glu Val Asn Ala Ala Lys Gin 4210 4215 4220
Ala Leu Asn Gly Asn Asp Asn Leu Ala Asn Ala Lys Gin Gin Ala Lys 4225 4230 4235 4240
Gin Gin Leu Ala Asn Leu Thr His Leu Asn Asp Ala Gin Lys Gin Ser 4245 4250 4255
Phe Glu Ser Gin lie Thr Gin Ala Pro Leu Val Thr Asp Val Thr Thr 4260 4265 4270
He Asn Gin Lys Ala Gin Thr Leu Asp His Ala Met Glu Leu Leu Arg 4275 4280 4285
Asn Ser Val Ala Asp Asn Gin Thr Thr Leu Ala Ser Glu Asp Tyr His 4290 4295 4300
Asp Ala Thr Ala Gin Arg Gin Asn Asp Tyr Asn Lys Ala Val Thr Ala 4305 4310 4315 4320
Ala Asn Asn lie lie Asn Gin Thr Thr Ser Pro Thr Met Asn Pro Asp 4325 4330 4335
Asp Val Asn Gly Ala Thr Thr Gin Val Asn Asn Thr Lys Val Ala Leu 4340 4345 4350
Asp Gly Asp Glu Asn Leu Ala Ala Ala Lys Gin Gin Ala Asn Asn Arg 4355 4360 4365
Leu Asp Gin Leu Asp His Leu Asn Asn Ala Gin Lys Gin Gin Leu Gin 4370 4375 4380
Ser Gin lie Thr Gin Ser Ser Asp lie Ala Ala Val Asn Gly His Lys 4385 4390 4395 4400 22 119629·序列表.doc 200815028
Gin Thr Ala Glu Ser Leu Asn Thr Ala Met Gly Asn Leu lie Asn Ala 4405 4410 4415 lie Ala Asp His Gin Ala Val Glu Gin Arg Gly Asn Phe lie Asn Ala 4420 4425 4430
Asp Thr Asp Lys Gin Thr Ala Tyr Asn Thr Ala Val Asn Glu Ala Ala 4435 4440 4445
Ala Met He Asn Lys Gin Thr Gly Gin Asn Ala Asn Gin Thr Glu Val 4450 4455 4460
Glu Gin Ala lie Thr Lys Val Gin Thr Thr Leu Gin Ala Leu Asn Gly 4465 4470 4475 4480
Asp His Asn Leu Gin Val Ala Lys Thr Asn Ala Thr Gin Ala lie Asp 4485 4490 4495
Val Leu Thr Ser Leu Asn Asp Pro Gin Lys Thr Ala Leu Lys Asp Gin 4500 4505 4510
Val Thr Ala Ala Thr Leu Val Thr Ala Val His Gin lie Glu Gin Asn 4515 4520 4525
Ala Asn Thr Leu Asn Gin Ala Met His Gly Leu Arg Gin Ser lie Gin 4530 4535 4540
Asp Asn Ala Ala Thr Lys Ala Asn Ser Lys Tyr lie Asn Glu Asp Gin 4545 4550 4555 4560
Pro Glu Gin Gin Asn Tyr Asp Gin Ala Val Gin Ala Ala Asn Asn lie 4565 4570 4575 lie Asn Glu Gin Thr Ala Thr Leu Asp Asn Asn Ala lie Asn Gin Val 4580 4585 4590
Ala Ala Thr Val Asn Thr Thr Lys Ala Ala Leu His Gly Asp Val Lys 4595 4600 4605
Leu Gin Asn Asp Lys Asp His Ala Lys Gin Thr Val Ser Gin Leu Ala 4610 4615 4620
His Leu Asn Asn Ala Gin Lys His Met Glu Asp Thr Leu lie Asp Ser 4625 4630 4635 4640
Glu Thr Thr Arg Thr Ala Val Lys Gin Asp Leu Thr Glu Val Gin Ala 4645 4650 4655
Leu Asp Gin Leu Met Asp Ala Leu Gin Gin Ser He Ala Asp Lys Asp 4660 4665 4670
Ala Thr Arg Ala Ser Ser Ala Tyr Val Asn Ala Glu Pro Asn Lys Lys 4675 4680 4685
Gin Ala Tyr Asp Glu Ala Val Gin Asn Ala Glu Ser lie He Ala Gly 4690 4695 4700
Leu Asn Asn Pro Thr lie Asn Lys Gly Asn Val Ser Ser Ala Thr Gin 4705 4710 4715 4720
Ala Val lie Ser Ser Lys Asn Ala Leu Asp Gly Val Glu Arg Leu Ala 4725 4730 4735
Gin Asp Lys Gin Thr Ala Gly Asn Ser Leu Asn His Leu Asp Gin Leu 4740 4745 4750
Thr Pro Ala Gin Gin Gin Ala Leu Glu Asn Gin lie Asn Asn Ala Thr 4755 4760 4765
Thr Cys Asp Lys Val Ala Glu lie lie Ala Gin Ala Gin Ala Leu Asn 4770 4775 4780
Glu Ala Met Lys Ala Leu Lys Glu Ser lie Lys Asp Gin Pro Gin Thr 4785 4790 4795 4800
Glu Ala Ser Ser Lys Phe He Asn Glu Asp Gin Ala Gin Lys Asp Ala 4805 4810 4815
Tyr Thr Gin Ala Val Gin His Ala Lys Asp Leu lie Asn Lys Thr Thr 4820 4825 4830
Asp Pro Thr Leu Ala Lys Ser lie lie Asp Gin Ala Thr Gin Ala Val 4835 4840 4845
Thr Asp Ala Lys Asn Asn Leu His Gly Asp Gin Lys Leu Ala Gin Asp 4850 4855 4860
Lys Gin Arg Ala Thr Glu Thr Leu Asn Asn Leu Ser Asn Leu Asn Thr 4865 4870 4875 4880
Pro Gin Arg Gin Ala Leu Glu Asn Gin He Asn Asn Ala Ala Thr Arg 4885 4890 4895
Gly Glu Val Ala Gin Lys Leu Thr Glu Ala Gin Ala Leu Asn Gin Ala 4900 4905 4910
Met Glu Ala Leu Arg Asn Ser lie Gin Asp Gin Gin Gin Thr Glu Ser 4915 4920 4925
Gly Ser Lys Phe lie Asn Glu Asp Lys Pro Gin Lys Asp Ala Tyr Gin 4930 4935 4940
Ala Ala Val Gin Asn Ala Lys Asp Leu lie Asn Gin Thr Gly Asn Pro 4945 4950 4955 4960
Thr Leu Asp Lys Ala Gin Val Glu Gin Leu Thr His Ala Phe Lys Gin 4965 4970 4975
Ala Lys Asp Asn Leu His Gly Asp Gin Lys Leu Ala Asp Asp Lys Gin 4980 4985 4990
His Ala Val Thr Asp Leu Asn Gin Leu Asn Gly Leu Asn Asn Pro Gin 23- 119629·序列表.doc 200815028 4995 5000 5005
Arg Gin Ala Leu Glu Ser Gin lie Asn Asn Ala Ala Thr Arg Gly Glu 5010 5015 5020
Val Ala Gin Lys Leu Ala Glu Ala Lys Ala Leu Asp Gin Ala Met Gin 5025 5030 5035 5040
Ala Leu Arg Asn Ser lie Gin Asp Gin Gin Gin Thr Glu Ala Gly Ser 5045 5050 5055
Lys Phe lie Asn Glu Asp Lys Pro Gin Lys Asp Ala Tyr Gin Ala Ala 5060 5065 5070
Val Gin Asn Ala Lys Asp Leu He Asn Gin Thr Gly Asn Pro Thr Leu 5075 5080 5085
Asp Lys Ser Gin Val Glu Gin Leu Thr Gin Ala Val Thr Thr Ala Lys 5090 5095 5100
Asp Asn Leu His Gly Asp Gin Lys Leu Ala Arg Asp Gin Gin Gin Ala 5105 5110 5115 5120
Val Thr Thr Val Asn Ala Leu Pro Asn Leu Asn His Ala Gin Gin Gin 5125 5130 5135
Thr Leu Thr Asp Ala lie Asn Ala Ala Pro Thr Arg Thr Glu Val Ala 5140 5145 5150
Gin His Val Gin Thr Ala Thr Glu Leu Asp His Ala Met Glu Thr Leu 5155 5160 5165
Lys Asn Lys Val Asp Gin Val Asn Thr Asp Lys Ala Gin Pro Asn Tyr 5170 5175 5180
Thr Glu Ala Ser Thr Asp Lys Lys Glu Ala Val Asp Gin Ala Leu Gin 5185 5190 5195 5200
Ala Ala Gin Ser lie Thr Asp Pro Thr Asn Gly Ser Asn Ala Asn Lys 5205 5210 5215
Asp Ala Val Glu Gin Ala Leu Thr Lys Leu Gin Glu Lys Val Asn Glu 5220 5225 5230
Leu Asn Gly Asn Glu Arg Val Ala Glu Ala Lys Thr Gin Ala Lys Gin 5235 5240 5245
Thr lie Asp Gin Leu Thr His Leu Asn Ala Asp Gin lie Ala Thr Ala 5250 5255 5260
Lys Gin Asn lie Asp Gin Ala Thr Lys Leu Gin Pro lie Ala Glu Leu 5265 5270 5275 5280
Val Asp Gin Ala Thr Gin Leu Asn Gin Ser Met Asp Gin Leu Gin Gin 5285 5290 5295
Ala Val Asn Glu His Ala Asn Val Glu Gin Thr lie Asp Tyr Thr Gin 5300 5305 5310
Ala Asp Ser Asp Lys Gin Lys Ala Tyr Lys Gin Ala lie Ala Asp Ala 5315 5320 5325
Glu Asn Val Leu Lys Gin Asn Ala Asn Lys Gin Gin Val Asp Gin Ala 5330 5335 5340
Leu Gin Asn lie Leu Asn Ala Lys Gin Ala Leu Asn Gly Asp Glu Arg 5345 5350 5355 5360
Val Ala Leu Ala Lys Thr Asn Gly Lys His Asp He Asp Gin Leu Asn 5365 5370 5375
Ala Leu Asn Asn Ala Gin Gin Asp Gly Fhe Lys Gly Arg lie Asp Gin 5380 5385 5390
Ser Asn Asp Leu Asn Gin lie Gin Gin lie Val Asp Glu Ala Lys Ala 5395 5400 5405
Leu Asn Arg Ala Met Asp Gin Leu Ser Gin Glu He Thr Gly Asn Glu 5410 5415 5420
Gly Arg Thr Lys Gly Ser Thr Asn Tyr Val Asn Ala Asp Thr Gin Val 5425 5430 5435 5440
Lys Gin Val Tyr Asp Glu Ala Val Asp Lys Ala Lys Gin Ala Leu Asp 5445 5450 5455
Lys Ser Ser Gly Gin Asn Leu Thr Ala Glu Gin Val lie Lys Leu Asn 5460 5465 5470
Asp Ala Val Thr Ala Ala Lys Lys Ala Leu Asn Gly Glu Glu Arg Leu 5475 5480 5485
Asn Asn Arg Lys Ala Glu Ala Leu Gin Arg Leu Asp Gin Leu Thr His 5490 5495 5500
Leu Asn Asn Ala Gin Arg Gin Leu Ala lie Gin Gin He Asn Asn Ala 5505 5510 5515 5520
Glu Thr Leu Asn Lys Ala Ser Arg Ala lie Asn Arg Ala Thr Lys Leu 5525 5530 5535
Asp Asn Ala Met Gly Ala Val Gin Gin Tyr lie Asp Glu Gin His Leu 5540 5545 5550
Gly Val lie Ser Ser Thr Asn Tyr lie Asn Ala Asp Asp Asn Leu Lys 5555 5560 5565
Ala Asn Tyr Asp Asn Ala lie Ala Asn Ala Ala His Glu Leu Asp Lys 5570 5575 5580
Val Gin Gly Asn Ala lie Ala Lys Ala Glu Ala Glu Gin Leu Lys Gin 5585 5590 5595 5600 24 119629-序列表.doc 200815028
Asn lie lie Asp Ala Gin Asn Ala Leu Asn Gly Asp Gin Asn Leu Ala 5605 5610 5615
Asn Ala Lys Asp Lys Ala Asn Ala Phe Val Asn Ser Leu Asn Gly Leu 5620 5625 5630
Asn Gin Gin Gin Gin Asp Leu Ala His Lys Ala lie Asn Asn Ala Asp 5635 5640 5645
Thr Val Ser Asp Val Ihr Asp lie Val Asn Asn Gin lie Asp Leu Asn 5650 5655 5660
Asp Ala Met Glu Thr Leu Lys His Leu Val Asp Asn Glu He Pro Asn 5665 5670 5675 5680
Ala Glu Gin Thr Val Asn Tyr Gin Asn Ala Asp Asp Asn Ala Lys Thr 5685 5690 5695
Asn Phe Asp Asp Ala Lys Arg Leu Ala Asn Thr Leu Leu Asn Ser Asp 5700 5705 5710
Asn Thr Asn Val Asn Asp He Asn Gly Ala He Gin Ala Val Asn Asp 5715 5720 5725
Ala He His Asn Leu Asn Gly Asp Gin Arg Leu Gin Asp Ala Lys Asp 5730 5735 5740
Lys Ala lie Gin Ser He Asn Gin Ala Leu Ala Asn Lys Leu Lys Glu 5745 5750 5755 5760
He Glu Ala Ser Asn Ala Thr Asp Gin Asp Lys Leu lie Ala Lys Asn 5765 5770 5775
Lys Ala Glu Glu Leu Ala Asn Ser lie lie Asn Asn lie Asn Lys Ala 5780 5785 5790
Thr Ser Asn Gin Ala Val Ser Gin Val Gin Thr Ala Gly Asn His Ala 5795 5800 5805
lie Glu Gin Val His Ala Asn Glu lie Pro Lys Ala Lys He Asp Ala 5810 5815 5820
Asn Lys Asp Val Asp Lys Gin Val Gin Ala Leu lie Asp Glu lie Asp 5825 5830 5835 5840
Arg Asn Pro Asn Leu Thr Asp Lys Glu Lys Gin Ala Leu Lys Asp Arg 5845 5850 5855
He Asn Gin lie Leu Gin Gin Gly His Asn Asp He Asn Asn Ala Leu 5860 5865 5870
Thr Lys Glu Glu He Glu Gin Ala Lys Ala Gin Leu Ala Gin Ala Leu 5875 5880 5885
Gin Asp He Lys Asp Leu Val Lys Ala Lys Glu Asp Ala Lys Gin Asp 5890 5895 5900
Val Asp Lys Gin Val Gin Ala Leu lie Asp Glu lie Asp Gin Asn Pro 5905 5910 5915 5920
Asn Leu Thr Asp Lys Glu Lys Gin Ala Leu Lys Asp Arg lie Asn Gin 5925 5930 5935 lie Leu Gin Gin Gly His Asn Gly lie Asn Asn Ala Met Thr Lys Glu 5940 5945 5950
Glu lie Glu Gin Ala Lys Ala Gin Leu Ala Gin Ala Leu Lys Glu He 5955 5960 5965
Lys Asp Leu Val Lys Ala Lys Glu Asn Ala Lys Gin Asp Val Asp Lys 5970 5975 5980
Gin Val Gin Ala Leu lie Asp Glu He Asp Gin Asn Pro Asn Leu Thr 5985 5990 5995 6000
Asp Lys Glu Lys Gin Ala Leu Lys Asp Arg He Asn Gin lie Leu Gin 6005 6010 6015
Gin Gly His Asn Asp lie Asn Asn Ala Met Thr Lys Glu Glu lie Glu 6020 6025 6030
Gin Ala Lys Ala Gin Leu Ala Gin Ala Leu Gin Asp lie Lys Asp Leu 6035 6040 6045
Val Lys Ala Lys Glu Asp Ala Lys Asn Ala lie Lys Ala Leu Ala Asn 6050 6055 6060
Ala Lys Arg Asp Gin lie Asn Ser Asn Pro Asp Leu Thr Pro Glu Gin 6065 6070 6075 6080
Lys Ala Lys Ala Leu Lys Glu lie Asp Glu Ala Giu Lys Arg Ala Leu 6085 6090 6095
Gin Asn Val Glu Asn Ala Gin Thr lie Asp Gin Leu Asn Arg Gly Leu 6100 6105 6110
Asn Leu Gly Leu Asp Asp lie Arg Asn Thr His Val Trp Glu Val Asp 6115 6120 6125
Glu Gin Fro Ala Val Asn Glu lie Phe Glu Ala Thr Pro Glu Gin lie 6130 6135 6140
Leu Val Asn Gly Glu Leu lie Val His Arg Asp Asp lie lie Thr Glu 6145 6150 6155 6160
Gin Asp lie Leu Ala His lie Asn Leu lie Asp Gin Leu Ser Ala Glu 6165 6170 6175
Val lie Asp 丁hr Pro Ser Thr Ala Thr lie Ser Asp Ser Leu Thr Ala 6180 6185 6190 -25- 119629·序列表.doc 200815028
Lys Val Glu Val Thr Leu Leu Asp Gly Ser Lys Val lie Val Asn Val 6195 6200 6205
Pro Val Lys Val Val Giu Lys Glu Leu Ser Val Val Lys Gin Gin Ala 6210 6215 6220 lie Glu Ser He Glu Asn Ala Ala Gin Gin Lys lie Asp Glu He Asn 6225 6230 6235 6240
Asn Ser Val Thr Leu Thr Leu Glu Gin Lys Glu Ala Ala lie Ala Glu 6245 6250 6255
Val Asn Lys Leu Lys Gin Gin Ala lie Asp His Val Asn Asn Ala Pro 6260 6265 6270
Asp Val His Ser Val Glu Glu He Gin Gin Gin Glu Gin Ala Tyr lie 6275 6280 6285
Glu Gin Phe Asn Pro Glu Gin Phe Thr lie Glu Gin Ala Lys Ser Asn 6290 6295 6300
Ala lie Lys Ser lie Glu Asp Ala lie Gin His Met lie Asp Glu lie 6305 6310 6315 6320
Lys Ala Arg Thr Asp Leu Thr Asp Lys Glu Lys Gin Glu Ala lie Ala 6325 6330 6335
Lys Leu Asn Gin Leu Lys Glu Gin Ala lie Glo Ala lie Gin Arg Ala 6340 6345 6350
Gin Ser lie Ser Glu lie Thr Glu Gin Leu Glu Gin Phe Lys Ala Gin 6355 6360 6365
Met Lys Ala Ala Asn Pro Thr Ala Lys Glu Leu Ala Lys Arg Lys Gin 6370 6375 6380
Glu Ala lie Ser Arg lie Lys Asp Phe Ser Asn Glu Lys lie Asn Ser 6385 6390 6395 6400 lie Arg Asn Ser Glu lie Gly Thr Ala Asp Giu Lys Gin Ala Ala Met
6405 6410 6415
Asn Gin lie Asn Glu lie Val Leu Glu Thr lie Arg Asp He Asn Asn 6420 6425 6430
Ala His Thr Leu Gin Gin Val Glu Ala Ala Leu Asn Asn Gly He Ala 6435 6440 6445
Arg lie Ser Ala Val Gin lie Val lie Ser Asp Arg Ala Lys Gin Ser 6450 6455 6460
Ser Ser Thr Gly Asn Glu Ser Asn Ser His Leu Thr lie Gly Tyr Gly 6465 6470 6475 6480
Thr Ala Asn His Pro Phe Asn Ser Ser Thr lie Gly His Lys Lys Lys 6485 6490 6495
Leu Asp Glu Asp Asp Asp lie Asp Pro Leu His Met Arg His Phe Ser 6500 6505 6510
Asn Asn Phe Gly Asn Val lie Lys Asn Ala He Gly Val Val Gly lie 6515 6520 6525
Ser Gly Leu Leu Ala Ser Phe Trp Phe Phe lie Ala Lys Arg Arg Arg 6530 6535 6540
Lys Glu Asp Glu Glu Glu Glu Leu Glu lie Arg Asp Asn Asn Lys Asp 6545 6550 6555 6560
Ser lie Lys Glu Thr Leu Asp Asp Thr Lys His Leu Pro Leu Leu Phe 6565 6570 6575
Ala Lys Arg Arg Arg Lys Glu Asp Glu Glu Asp Val Thr Val Glu Glu 6580 6585 6590
Lys Asp Ser Leu Asn Asn Gly Glu Ser Leu Asp Lys Val Lys His Thr 6595 6600 6605
Pro Phe Phe Leu Pro Lys Arg Arg Arg Lys Glu Asp Glu Glu Asp Val 6610 6615 6620
Glu Val Thr Asn Glu Asn Thr Asp Glu Lys Val Leu Lys Asp Asn Glu 6625 6630 6635 6640
His Ser Pro Leu Leu Fhe Ala Lys Arg Arg Lys Asp Lys Glu Glu Asp 6645 6650 6655
Val Glu Thr Thr Thr Ser lie Glu Ser Lys Asp Glu Asp Val Pro Leu 6660 6665 6670
Leu Leu Ala Lys Lys Lys Asn Gin Lys Asp Asn Gin Ser Lys Asp Lys 6675 6680 6685
Lys Ser Ala Ser Lys Asn Thr Ser Lys Lys Val Ala Ala Lys Lys Lys 6690 6695 6700
Lys Lys Lys Ser Lys Lys Asn Lys Lys 6705 6710 <210〉 14 <211〉 701 <212> PRT 〈213>葡萄球菌 26- 119629-序列表.doc 200815028 <400> 14
Met Asn Asn Arg Asp Lys Leu Gin Lys Phe Ser He Arg Lys Tyr Ala 1 5 10 15
He Gly Thr Phe Ser Thr Val lie Ala Thr Leu Val Phe Met Gly He 20 25 30
Asn Thr Asn His Ala Ser Ala Asp Glu Leu Asn Gin Asn Gin Lys Leu 35 40 45 lie Lys Gin Leu Asn Gin Thr Asp Asp Asp Asp Ser Asn Thr His Ser 50 55 60
Gin Glu He Glu Asn Asn Lys Gin Asn Ser Ser Gly Gin Thr Glu Ser 65 70 75 80
Leu Arg Ser Ser Thr Ser Gin Asn Gin Ala Asn Ala Arg Leo Ser Asp 85 90 95
Gin Phe Lys Asp Thr Asn Glu Thr Ser Gin Gin Leu Pro Thr Asn Val 100 105 110
Ser Asp Asp Ser lie Asn Gin Ser His Ser Glu Ala Asn Met Asn Asn 115 120 125
Glu Pro Leu Lys Val Asp Asn Ser Thr Met Gin Ala His Ser Lys He 130 135 140
Val Ser Asp Ser Asp Gly Asn Ala Ser Glu Asn Lys His His Lys Leu 145 150 155 160
Thr Glu Asn Val Leu Ala Glu Ser Arg Ala Ser Lys Asn Asp Lys Glu 165 170 175
Lys Glu Asn Leu Gin Glu Lys Asp Lys Ser Gin Gin Val His Pro Pro 180 185 190
Leu Asp Lys Asn Ala Leu Gin Ala Phe Phe Asp Ala Ser Tyr His Asn 195 200 205
Tyr Arg Met lie Asp Arg Asp Arg Ala Asp Ala Thr Glu Tyr Gin Lys 210 215 220
Val Lys Ser Thr Phe Asp Tyr Val Asn Asp Leu Leu Gly Asn Asn Gin 225 230 235 240
Asn lie Pro Ser Glu Gin Leu Val Ser Ala Tyr Gin Gin Leu Glu Lys 245 250 255
Ala Leu Glu Leu Ala Arg Thr Leu Pro Gin Gin Ser Thr Thr Glu Lys 260 265 270
Arg Gly Arg Arg Ser Thr Arg Ser Val Val Glu Asn Arg Ser Ser Arg 275 280 285
Ser Asp Tyr Leu Asp Ala Arg Thr Glu Tyr Tyr Val Ser Lys Asp Asp 290 295 300
Asp Asp Ser Gly Phe Pro Pro Gly Thr Phe Phe His Ala Ser Asn Arg 305 310 315 320
Arg Trp Pro Tyr Asn Leu Pro Arg Ser Arg Asn He Leu Arg Ala Ser 325 330 335
Asp Val Gin Gly Asn Ala Tyr lie Thr Thr Lys Arg Leu Lys Asp Gly 340 345 350
Tyr Gin Trp Asp lie Leu Phe Asn Ser Asn His Lys Gly His Glu Tyr 355 360 365
Met Tyr Tyr Trp Phe Gly Leu Pro Ser Asp Gin Thr Pro Thr Gly Pro 370 375 380
Val Thr Phe Thr He lie Asn Arg Asp Gly Ser Ser Thr Ser Thr Gly 385 390 395 400
Gly Val Gly Phe Gly Ser Gly Ala Pro Leu Pro Gin Phe Trp Arg Ser 405 410 415
Ala Gly Ala lie Asn Ser Ser Val Ala Asn Asp Phe Lys His Gly Ser 420 425 430
Ala Thr Asn Tyr Ala Phe Tyr Asp Gly Val Asn Asn Phe Ser Asp Phe 435 440 445
Ala Arg Gly Gly Glu Leu Tyr Phe Asp Arg Glu Gly Ala Thr Gin Thr 450 455 460
Asn Lys Tyr Tyr Gly Asp Glu Asn Phe Ala Leu Leu Asn Ser Glu Lys 465 470 475 480
Pro Asp Gin He Arg Gly Leu Asp Thr lie Tyr Ser Phe Lys Gly Ser 485 490 495
Gly Asp Vai Ser Tyr Arg lie Ser Phe Lys Thr Gin Gly Ala Pro Thr 500 505 510
Ala Arg Leu Tyr Tyr Ala Ala Gly Ala Arg Ser Gly Glu Tyr Lys Gin 515 520 525
Ala Thr Asn Tyr Asn Gin Leu Tyr Val Glu Pro Tyr Lys Asn Tyr Arg 530 535 540
Asn Arg Val Gin Ser Asn Val Gin Val Lys Asn Arg Thr Leu His Leu 545 550 555 560
Lys Arg Thr lie Arg Gin Phe Asp Pro Thr Leu Gin Arg Thr Thr Asp 565 570 575
Val Pro lie Leu Asp Ser Asp Gly Ser Gly Ser lie Asp Ser Val Tyr 27- 119629-序列表.doc 200815028 580 585 590
Asp Pro Leu Ser Tyr Val Lys Asn Val Thr Gly Thr Val Leu Gly lie 595 600 605
Tyr Pro Ser Tyr Leu Pro Tyr Asn Gin Glu Arg Trp Gin Gly Ala Asn 610 615 620
Ala Met Asn Ala Tyr Gin lie Glu Glu Leu Phe Ser Gin Glu Asn Leu 625 630 635 640
Gin Asn Ala Ala Arg Ser Gly Arg Pro He Gin Phe Leu Val Gly Phe 645 650 655
Asp Val Glu Asp Ser His His Asn Pro Glu Thr Leu Leu Pro Val Asn 660 665 670
Leu Tyr Val Lys Pro Glu Leu Lys His Thr lie Glu Leu Tyr His Asp 675 680 685
Asn Glu Lys Gin Asp Arg Lys Glu Phe Ser Val Ser Lys 690 695 700
<210> 15 <211> 9439 <212〉 PRT <213> ^^球菌 <400> Ϊ5
Met Ser Gly Thr Leu His Asn Thr Val Gly Ser Gly lie Leu Pro Tyr I 5 10 15
Gin Gin Glu lie Arg lie Lys Leu Thr Ser Asn Glu Pro lie Lys Asp 20 25 30
Ser Glu Trp Ser lie Thr Gly Tyr Pro Asn Thr Leu Thr Leu Gin Asn 35 40 45
Ala Val Gly Arg Thr Asn Asn Ala Thr Glu Lys Asn Leu Ala Leu Val 50 55 60
Gly His lie Asp Pro Gly Asn Tyr Phe lie Thr Val Lys Phe Gly Asp 65 70 75 80
Lys Val Glu Gin Phe Glu lie Arg Ser Lys Pro Thr Pro Pro Arg He 85 90 95 lie Thr Thr Ala Asn Glu Leu Arg Gly Asn Pro Asn His Lys Pro Glu 100 105 110 lie Arg Val Thr Asp lie Pro Asn Asp Thr Thr Ala Lys lie Lys Leu 115 120 125
Val Met Gly Gly Thr Asp Gly Asp His Asp Pro Glu lie Asn Pro Tyr 130 135 140
Thr Val Pro Glu Asn Tyr Thr Val Val Ala Glu Ala Tyr His Asp Asn 145 150 155 160
Asp Pro Ser Lys Asn Gly Val Leu Thr Fhe Arg Ser Ser Asp Tyr Leu 165 170 175
Lys Asp Leu Pro Leu Ser Gly Glu Leu Lys Ala lie Val Tyr Tyr Asn 180 185 190
Gin Tyr Val Gin Ser Asn Phe Ser Lys Ser Val Pro Phe Ser Ser Asp 195 200 205
Thr Thr Pro Pro Thr lie Asn Giu Pro Ala Gly Leu Vai His Lys Tyr 210 215 220
Tyr Arg Gly Asp His Val Glu lie Thr Leu Pro Val Thr Asp Asn Thr 225 230 235 240
Gly Gly Ser Gly Leu Arg Asp Val Asn Val Asn Leu Pro Gin Gly Trp 245 250 255
Thr Lys Thr Phe Thr lie Asn Pro Asn Asn Asn Thr Glu Gly Thr Leu 260 265 270
Lys Leu He Gly Asn He Pro Ser Asn Glu Ala Tyr Asn Thr Thr Tyr 275 280 285
His Phe Asn lie Thr Ala Thr Asp Asn Ser Gly Asn Thr Thr Asn Pro 290 295 300
Ala Lys Thr Phe lie Leu Asn Val Gly Lys Leu Ala Asp Asp Leu Asn 305 310 315 320
Pro Val Gly Leu Ser Arg Asp Gin Leu Gin Leu Val Thr Asp Fro Ser 325 330 335
Ser Leu Ser Asn Ser Glu Arg Glu Glu Val Lys Arg Lys lie Ser Glu 340 345 350
Ala Asn Ala Asn He Arg Ser Tyr Leu Leu Gin Asn Asn Pro lie Leu 355 360 365
Ala Gly Vai Asn Gly Asp Val Thr Phe Tyr Tyr Arg Asp Gly Ser Val 370 375 380
Asp Val lie Asp Ala Glu Asn Val lie Thr Tyr Glu Pro Glu Arg Lys 385 390 395 400 28· 119629·序列表.doc 200815028
Ser lie Phe Ser Glu Asn Gly Asn Thr Asn Lys Lys Glu Ala Val He 405 410 415
Thr He Ala Arg Gly Gin Asn Tyr Thr lie Gly Fro Asn Leu Arg Lys 420 425 430
Tyr Phe Ser Leu Ser Asn Gly Ser Asp Leu Pro Asn Arg Asp Phe Thr 435 440 445
Ser lie Ser Ala lie Gly Ser Leu Pro Ser Ser Ser Glu lie Ser Arg 450 455 460
Leu Asn Val Gly Asn Tyr Asn Tyr Arg Val Asn Ala Lys Asn Ala Tyr 465 470 475 480
His Lys Thr Gin Gin Glu Leu Asn Leu Lys Leu Lys lie Val Glu Val 485 490 495
Asn Ala Pro Thr Gly Asn Asn Arg Val Tyr Arg Val Ser Thr Tyr Asn 500 505 510
Leu Thr Asn Asp Glu lie Asn Lys lie Lys Gin Ala Phe Lys Ala Ala 515 520 525
Asn Ser Gly Leu Asn Leu Asn Asp Asn Asp He Thr Val Ser Asn Asn 530 535 540
Phe Asp His Arg Asn Val Ser Ser Val Thr Val Thr lie Arg Lys Gly 545 550 555 560
Asp Leu lie Lys Glu Phe Ser Ser Asn Leu Asn Asn Met Asn Phe Leu 565 570 575
Arg Trp Val Asn He Arg Asp Asp Tyr Thr lie Ser Trp Thr Ser Ser 580 585 590
Lys He Gin Gly Arg Asn Thr Asp Gly Gly Leu Glu Trp Ser Pro Asp 595 600 605
His Lys Ser Leu He Tyr Lys Tyr Asp Ala Thr Leu Gly Arg Gin lie 610 615 620
Asn Thr Asn Asp Val Leu Thr Leu Leu Gin Ala Thr Ala Lys Asn Ser 625 630 635 640
Asn Leu Arg Ser Asn lie Asn Ser Asn Glu Lys Gin Leu Ala Glu Arg 645 650 655
Gly Ser Asn Gly Tyr Ser Lys Ser He He Arg Asp Asp Gly Glu Lys 660 665 670
Ser Tyr Leo Leu Asn Ser Asn Pro lie Gin Val Leu Asp Leu Val Glu 675 680 685
Pro Asp Asn Gly Tyr Gly Gly Arg Gin Val Ser His Ser Asn Val lie 690 695 700
Tyr Asn Glu Lys Asn Ser Ser He Val Asn Gly Gin Val Pro Glu Ala 705 710 715 720
Asn Gly Ala Ser Ala Phe Asn He Asp Lys Val Val Lys Ala Asn Ala 725 730 735
Ala Asn Asn Gly lie Met Gly Val He Tyr Lys Ala Gin Leu Tyr Leu 740 745 750
Ala Pro Tyr Ser Pro Lys Gly Tyr lie Glu Lys Leu Gly Gin Asn Leu 755 760 765
Ser Asn Thr Asn Asn Val He Asn Val Tyr Phe Val Pro Ser Asp Lys 770 775 780
Val Asn Fro Ser lie Thr Val Gly Asn Tyr Asp His His Thr Val Tyr 785 790 795 800
Ser Gly Glu Thr Phe Lys Asn Thr lie Asn Val Asn Asp Asn Tyr Gly 805 810 815
Leu Asn Thr Val Ala Ser Thr Ser Asp Ser Ala lie Thr Met Thr Arg 820 825 830
Asn Asn Asn Glu Leu Val Gly Gin Ala Pro Asn Val Thr Asn Ser lie 835 840 845
Asn Lys lie Val Lys Val Lys Ala Thr Asp Lys Ser Gly Asn Glu Ser 850 855 860
He Val Ser Phe Thr Val Asn lie Lys Pro Leu Asn Glu Lys Tyr Arg 865 870 875 880 lie Thr Thr Ser Ser Ser Asn Gin Thr Pro Val Arg lie Ser Asn lie 885 890 895
Gin Asn Asn Ala Asn Leu Ser lie Glu Asp Gin Asn Arg Val Lys Ser 900 905 910
Ser. Leu Ser Met Thr Lys lie Leu Gly Thr Arg Asn Tyr Val Asn Glu 915 920 925
Ser Asn Asn Asp Val Arg Ser Gin Val Val Ser Lys Val Asn Arg Ser 930 935 940
Gly Asn Asn Ala Thr Val Asn Val Thr Thr Thr Phe Ser Asp Gly Thr 945 950 955 960
Thr Asn Thr lie Thr Val Pro Val Lys His Val Leu Leu Glu Val Val 965 970 975
Pro Thr Thr Arg Thr Thr Val Arg Gly Gin Gin Phe Pro Thr Gly Lys 980 985 990 -29- 119629-序列表.doc 200815028
Gly Thr Ser Pro Asn Asp Phe Phe Ser Leu Arg Thr Gly Gly Pro Val 995 1000 1005
Asp Ala Arg lie Val Trp Val Asn Asn Gin Gly Pro Asp lie Asn Ser 1010 1015 1020
Asn Gin lie Gly Arg Asp Leu Thr Leu His Ala Glu lie Phe Phe Asp 1025 1030 1035 1040
Gly Glu Thr Thr Pro lie Arg Lys Asp Thr Thr Tyr Lys Leu Ser Gin 1045 1050 1055
Ser lie Pro Lys Gin lie Tyr Glu Thr Thr lie Asn Gly Arg Phe Asn 1060 1065 1070
Ser Ser Gly Asp Ala Tyr Fro Gly Asn Phe Val Gin Ala Val Asn Gin 1075 1080 1085
Tyr Trp Pro Glu His Met Asp Phe Arg Trp Ala Gin Gly Ser Gly Thr 1090 1095 1100
Pro Ser Ser Arg Asn Ala Gly Ser Phe Thr Lys Thr Val Thr Val Val 1105 1110 1115 1120
Tyr Gin Asn Gly Gin Thr Glu Asn Val Asn Val Leu Phe Lys Val Lys 1125 1130 1135
Pro Asn Lys Pro Val lie Asp Ser Asn Ser Val lie Ser Lys Gly Gin 1140 1145 1150
Leu Asn Gly Gin Gin lie Leu Val Arg Asn Val Pro Gin Asn Ala Gin 1155 1160 1165
Val Thr Leu Tyr Gin Ser Asn Gly Thr Val lie Pro Asn Thr Asn Thr 1170 1175 1180
Thr lie Asp Ser Asn Gly lie Ala Thr Val Thr He Gin Gly Thr Leu 1185 1190 1195 1200
Pro Thr Gly Asn lie Thr Ala Lys Thr Ser Met Thr Asn Asn Val Thr 1205 1210 1215
Tyr Thr Lys Gin Asn Ser Ser Gly lie Ala Ser Asn Thr Thr Glu Asp 1220 1225 1230 lie Ser Val Phe Ser Glu Asn Ser Asp Gin Val Asn Val Thr Ala Gly 1235 1240 1245
Met Gin Ala Lys Asn Asp Gly lie Lys lie He Lys Gly Thr Asn Tyr 1250 1255 1260
Asn Phe Asn Asp Phe Asn Ser Phe lie Ser Asn lie Pro Ala His Ser 1265 1270 1275 1280
Thr Leu Thr Trp Asn Glu Glu Pro Asn Ser Trp Lys Asn Asn He Gly 1285 1290 1295
Thr Thr Thr Lys Thr Val Thr Val Thr Leu Pro Asn His Gin Gly Thr 1300 1305 1310
Arg Thr Val Asp lie Pro lie Thr lie Tyr Pro Thr Val Thr Ala Lys 1315 1320 1325
Asn Pro Val Arg Asp Gin Lys Gly Arg Asn Leu Thr Asn Gly Thr Asp 1330 1335 1340
Val Tyr Asn Tyr lie lie Phe Glu Asn Asn Asn Arg Leu Gly Gly Thr 1345 1350 1355 1360
Ala Ser Trp Lys Asp Asn Arg Gin Pro Asp Lys Asn lie Ala Gly Val 1365 1370 1375
Gin Asn Leu He Ala Leu Val Asn Tyr Pro Gly He Ser Thr Pro Leu 1380 1385 1390
Glu Val Pro Val Lys Val Trp Val Tyr Asn Phe Asp Phe Thr Gin Pro 1395 1400 1405
He Tyr Lys lie Gin Val Gly Asp Thr Phe Pro Lys Gly Thr Trp Ala 1410 1415 1420
Gly Tyr Tyr Lys His Leu Glu Asn Gly Glu Gly Leu Pro lie Asp Gly 1425 1430 1435 1440
Trp Lys Phe Tyr Trp Asn Gin Gin Ser Thr Gly Thr Thr Ser Asp Gin 1445 1450 1455
Trp Gin Ser Leu Ala Tyr Thr Arg Thr Pro Phe Val Lys Thr Gly Thr 1460 1465 1470
Tyr Asp Val Val Asn Pro Ser Asn Trp Gly Val Trp Gin Thr Ser Gin 1475 1480 1485
Ser Ala Lys Phe lie Val Thr Asn Ala Lys Pro Asn Gin Pro Thr lie 1490 1495 1500
Thr Gin Ser Lys Thr Gly Asp Val Thr Val Thr Pro Gly Ala Val Arg 1505 1510 1515 1520
Asn lie Leu 'lie Ser Gly Thr Asn Asp Tyr lie Gin Ala Ser Ala Asp 1525 1530 1535
Lys He Val lie Asn Lys Asn Gly Asn Lys Leu Thr Thr Phe Val Lys 1540 1545 1550
Asn Asn Asp Gly Arg Trp Thr Val Glu Thr Gly Ser Pro Asp lie Asn 1555 1560 1565
Gly lie Gly Pro Thr Asn Asn Gly Thr Ala lie Ser Leu Ser Arg Leu 1570 1575 1580
Ala Val Arg Pro Gly Asp Ser lie Glu Ala lie Ala Thr Glu Gly Ser j 30- 119629-序列表.doc 200815028 1585 1590 1595 1600
Gly Glu Thr He Ser Thr Ser Ala Thr Ser Glu He Tyr He Val Lys 1605 1610 1615
Ala Pro Gin Pro Glu Gin Val Ala Thr His Thr Tyr Asp Asn Gly Thr 1620 1625 1630
Phe Asp lie Leu Pro Asp Asn Ser Arg Asn Ser Leu Asn Pro Thr Glu 1635 1640 1645
Arg Val Glu He Asn Tyr Thr Glu Lys Leu Asn Gly Asn Glu Thr Gin 1650 1655 1660
Lys Ser Phe Thr lie Thr Lys Asn Asn Asn Gly Lys Trp Thr lie Asn 1665 1670 1675 1680
Asn Lys Pro Asn Tyr Val Glu Phe Asn Gin Asp Asn Gly Lys Val Val 1685 1690 1695
Phe Ser Ala Asn Thr lie Lys Pro Asn Ser Gin lie Thr lie Thr Pro 1700 1705 1710
Lys Ala Gly Gin Gly Asn Thr Glu Asn Thr Asn Pro Thr Val lie Gin 1715 1720 1725
Ala Pro Ala Gin His Thr Leu Thr lie Asn Glu lie Val Lys Glu Gin 1730 1735 1740
Gly Gin Asn Val Thr Asn Asp Asp lie Asn Asn Ala Val Gin Val Pro 1745 1750 1755 1760
Asn Lys Asn Arg Val Ala lie Lys Gin Gly Asn Ala Leu Pro Thr Asn 1765 1770 1775
Leu Ala Gly Gly Ser Thr Ser His lie Pro Val Val lie Tyr Tyr Ser 1780 1785 1790
Asp Gly Ser Ser Glu Glu Ala Thr Glu Thr Val Arg Thr Lys Val Asn 1795 1800 1805
Lys Thr Glu Leu He Asn Ala Arg Arg Arg Leu Asp Glu Glu lie Ser 1810 1815 1820
Lys Glu Asn Lys Thr Pro Ser Ser He Arg Asn Phe Asp Gin Ala Met 1825 1830 1835 1840
Asn Arg Ala Gin Ser Gin He Asn Thr Ala Lys Ser Asp Ala Asp Gin 1845 1850 1855
Val lie Gly Thr Glu Phe Ala Thr Pro Gin Gin Val Asn Ser Ala Leu 1860 1865 1870
Ser Lys Val Gin Ala Ala Gin Asn Lys lie Asn Glu Ala Lys Ala Leu 1875 1880 1885
Leu Gin Asn Lys Ala Asp Asn Ser Gin Leu Val Arg Ala Lys Glu Gin 1890 1895 1900
Leu Gin Gin Ser lie Gin Pro Ala Ala Ser Thr Asp Gly Met Thr Gin 1905 1910 1915 1920
Asp Ser 了hr Arg Asn Tyr Asn Asn Lys Arg Gin Ala Ala Glu Gin Ala 1925 1930 1935 lie Gin His Ala Asn Ser Val lie Asn Asn Gly Asp Ala Thr Ser Gin 1940 1945 1950
Gin lie Asn Asp Ala Lys Asn Thr Val Glu Gin Ala Gin Arg Asp Tyr 1955 1960 1965
Val Glu Ala Lys Ser Asn Leu Arg Ala Asp Lys Ser Gin Leu Gin Ser 1970 1975 1980
Ala Tyr Asp Thr Leu Asn Arg Asp Val Leu Thr Asn Asp Lys Lys Pro 1985 1990 1995 2000
Ala Ser Val Arg Arg Tyr Asn Glu Ala lie Ser Asn lie Arg Lys Glu 2005 2010 2015
Leu Asp Thr Ala Lys Ala Asp Ala Ser Ser Thr Leu Arg Asn Thr Asn 2020 2025 2030
Pro Ser Val Glu Gin Val Arg Asp Ala Leu Asn Lys lie Asn Thr Val 2035 2040 2045
Gin Pro Lys Val Asn Gin Ala lie Ala Leu Leu Gin Pro Lys Glu Asn 2050 2055 2060
Asn Ser Glu Leu Val Gin Ala Lys Lys Arg Leu Gin Asp Ala Yal Asn 2065 2070 2075 2080
Asp lie Pro Gin Thr Gin Gly Met Thr Gin Gin Thr He Asn Asn Tyr 2085 2090 2095
Asn Asp Lys Gin Arg Glu Ala Glu Arg Ala Leu Thr Ser Ala Gin Arg 2100 2105 · 2110
Val lie Asp Asn Gly Asp Ala Thr Thr Gin Glu lie Thr Ser Glu Lys 2115 2120 2125
Ser Lys Val Glu Gin Ala Met Gin Ala Leu Thr Asn Ala Lys Ser Asn 2130 2135 2140
Leu Arg Ala Asp Lys Asn Glu Leu Gin Thr Ala Tyr Asn Lys Leu lie 2145 2150 2155 2160
Glu Asn Val Ser Thr Asn Gly Lys Lys Pro Ala Ser lie Arg Gin Tyr 2165 2170 2175
Glu Thr Ala Lys Ala Arg lie Gin Asn Gin lie Asn Asp Ala Lys Asn 2180 2185 2190 -31 - 119629-序列表.doc 200815028
Glu Ala Glu Arg lie Leu Gly Asn Asp Asn Pro Gin Val Ser Gin Val 2195 2200 2205
Thr Gin Ala Leu Asn Lys lie Lys Ala He Gin Pro Lys Leu Thr Glu 2210 2215 2220
Ala lie Asn Met Leu Gin Asn Lys Glu Asn Asn Thr Glu Leu Val Asn 2225 2230 2235 2240
Ala Lys Asn Arg Leu Glu Asn Ala Val Asn Asp Thr Asp Pro Thr His 2245 2250 2255
Gly Met Thr Gin Glu Thr lie Asn Asn Tyr Asn Ala Lys Lys Arg Glu 2260 2265 2270
Ala Gin Asn Glu lie Gin Lys Ala Asn Met lie He Asn Asn Gly Asp 2275 2280 2285
Ala Thr Ala Gin Asp He Ser Ser Glu Lys Ser Lys Val Glu Gin Val 2290 2295 2300
Leu Gin Ala Leu Gin Asn Ala Lys Asn Asp Leu Arg Ala Asp Lys Arg 2305 2310 2315 2320
Glu Leu Gin Thr Ala Tyr Asn Lys Leu lie Gin Asn Val Asn Thr Asn 2325 2330 2335
Gly Lys Lys Pro Ser Ser lie Gin Asn Tyr Lys Ser Ala Arg Arg Asn 2340 2345 2350 lie Glu Asn Gin Tyr Asn Thr Ala Lys Asn Glu Ala His Asn Val Leu 2355 2360 2365
Glu Asn Thr Asn Pro Thr Val Asn Ala Val Glu Asp Ala Leu Arg Lys 2370 2375 2380 lie Asn Ala He Gin Pro Glu Val Thr Lys Ala lie Asn lie Leu Gin 2385 2390 2395 2400
Asp Lys Glu Asp Asn Ser Glu Leu Val Arg Ala Lys Glu Lys Leu Asp 2405 2410 2415
Gin Ala He Asn Ser Gin Pro Ser Leu Asn Gly Met Thr Gin Glu Ser 2420 2425 2430 lie Asn Asn Tyr Thr Thr Lys Arg Arg Glu Ala Gin Asn He Ala Ser 2435 2440 2445
Ser Ala Asp Thr He He Asn Asn Gly Asp Ala Ser He Glu Gin lie 2450 2455 2460
Thr Glu Asn Lys lie Arg Val Glu Glu Ala Thr Asn Ala Leu Asn Glu 2465 2470 2475 2480
Ala Lys Gin His Leu Thr Ala Asp Thr Thr Ser Leu Lys Thr Glu Val 2485 2490 2495
Arg Lys Leu Ser Arg Arg Gly Asp Thr Asn Asn Lys Lys Fro Ser Ser 2500 2505 2510
Val Ser Ala Tyr Asn Asn Thr lie His Ser Leu Gin Ser Glu He Thr 2515 2520 2525
Gin Thr Glu Asn Arg Ala Asn Thr lie lie Asn Lys Pro lie Arg Ser 2530 2535 2540
Val Glu Glu Val Asn Asn Ala Leu His Glu Val Asn Gin Leu Asn Gin 2545 2550 2555 2560
Arg Leu Thr Asp Thr lie Asn Leu Leu Gin Fro Leu Ala Asn Lys Glu 2565 2570 2575
Ser Leu Lys Glu Ala Arg Asn Arg Leu Glu Ser Lys lie Asn Glu Thr 2580 2585 2590
Val Gin Thr Asp Gly Met Thr Gin Gin Ser Val Glu Asn Tyr Lys Gin 2595 2600 2605
Ala Lys lie Lys Ala Gin Asn Glu Ser Ser He Ala Gin Thr Leu lie 2610 2615 2620
Asn Asn Gly Asp Ala Ser Asp Gin Glu Val Ser Thr Glu He Glu Lys 2625 2630 2635 2640
Leu Asn Gin Lys Leu Ser Glu Leu Thr Asn Ser lie Asn His Leu Thr 2645 2650 2655
Val Asn Lys Glu Pro Leu Glu Thr Ala Lys Asn Gin Leu Gin Ala Asn 2660 2665 2670 lie Asp Gin Lys Pro Ser Thr Asp Gly Met Thr Gin Gin Ser Val Gin 2675 2680 2685
Ser Tyr Glu Arg Lys Leu Gin Glu Ala Lys Asp Lys lie Asn Ser lie 2690 2695 2700
Asn Asn Val Leii Ala Asn Asn Pro Asp Val Asn Ala lie Arg Thr Asn 2705 2710 2715 2720
Lys Val Glu Thr Glu Gin lie Asn Asn Glu Leu Thr Gin Ala Lys Gin 2725 2730 2735
Gly Leu Thr Val Asp Lys Gin Pro Leu lie Asn Ala Lys Thr Ala Leu 2740 2745 2750
Gin Gin Ser Leu Asp Asn Gin Pro Ser Thr Thr Gly Met Thr Glu Ala 2755 2760 2765
Thr lie Gin Asn Tyr Asn Ala Lys Arg Gin Lys Ala Glu Gin Val lie 2770 2775 2780
Gin Asn Ala Asn Lys He lie Glu Asn Ala Gin Pro Ser Val Gin Gin 32· 119629-序列表.doc 200815028 2785 2790 2795 2800
Val Ser Asp Glu Lys Ser Lys Val Glu Gin Ala Leu Ser GIu Leu Asn 2805 2810 2815
Asn Ala Lys Ser Ala Leu Arg Ala Asp Lys Gin Glu Leu Gin Gin Ala 2820 2825 2830
Tyr Asn Gin Leu lie Gin Pro Thr Asp Leu Asn Asn Lys Lys Pro Ala 2835 2840 2845
Ser He Thr Ala Tyr Asn Gin Arg Tyr Gin Gin Phe Ser Asn Glu Leu 2850 2855 2860
Asn Ser Thr Lys Thr Asn Thr Asp Arg lie Leu Lys Glu Gin Asn Pro 2865 2870 2875 2880
Ser Val Ala Asp Val Asn Asn Ala Leu Asn Lys Val Arg Glu Val Gin 2885 2890 2895
Gin Lys Ley Asn Glu Ala Arg Ala Leu Leu Gin Asn Lys Glu Asp Asn 2900 2905 2910
Ser Ala Leu Val Arg Ala Lys Glu Gin Leu Gin Gin Ala Val Asp Gin 2915 2920 2925
Val Pro Ser Thr Glu Gly Met Thr Gin Gin Thr Lys Asp Asp Tyr Asn 2930 2935 2940
Ser Lys Gin Gin Ala Ala Gin Gin Glu lie Ser Lys Ala Gin Gin Val 2945 2950 2955 2960 lie Asp Asn Gly Asp Ala Thr Thr Gin Gin lie Ser Asn Ala Lys Thr 2965 2970 2975
Asn Val Glu Arg Ala Leu Glu Ala Leu Asn Asn Ala Lys Thr Gly Leu 2980 2985 2990
Arg Ala Asp Lys Glu Glu Leu Gin Asn Ala Tyr Asn Gin Leu Thr Gin 2995 3000 3005
Asn lie Asp Thr Ser Gly Lys Thr Pro Ala Ser lie Arg Lys Tyr Asn 3010 3015 3020
Glu Ala Lys Ser Arg He Gin Thr Gin He Asp Ser Ala Lys Asn Glu 3025 3030 3035 3040
Ala Asn Ser He Leu Thr Asn Asp Asn Pro Gin Val Ser Gin Val Thr 3045 3050 3055
Ala Ala Leu Asn Lys lie Lys Ala Val Gin Pro Glu Leu Asp Lys Ala 3060 3065 3070 lie Ala Met Leu Lys Asn Lys Glu Asn Asn Asn Ala Leu Val Gin Ala 3075 3080 3085
Lys Gin Gin Leu Gin Gin lie Val Asn Glu Val Asp Pro Thr Gin Gly 3090 3095 3100
Met Thr Thr Asp Thr Ala Asn Asn Tyr Lys Ser Lys Lys Arg Glu Ala 3105 3110 3115 3120
Glu Asp Glu lie Gin Lys Ala Gin Gin He lie Asn Asn Gly Asp Ala 3125 3130 3135
Thr Glu Gin Gin lie Thr Asn Glu Thr Asn Arg Val Asn Gin Ala lie 3140 3145 3150
Asn Ala He Asn Lys Ala Lys Asn Asp Leu Arg Ala Asp Lys Ser Gin 3155 3160 3165
Leu Glu Asn Ala Tyr Asn Gin Leu lie Gin Asn Val Asp Thr Asn Gly 3170 3175 3180
Lys Lys Pro Ala Ser He Gin Gin Tyr Gin Ala Ala Arg Gin Ala lie 3185 3190 3195 3200
Glu Thr Gin Tyr Asn Asn Ala Lys Ser Glu Ala His Gin He Leu Glu 3205 3210 3215
Asn Ser Asn Pro Ser Val Asn Glu Val Ala Gin Ala Leu Gin Lys Val 3220 3225 3230
Glu Ala Val Gin Leu Lys Val Asn Asp Ala lie His lie Leu Gin Asn 3235 3240 3245
Lys Glu Asn Asn Ser Ala Leu Val Thr Ala Lys Asn Gin Leu Gin Gin 3250 3255 3260
Ser Val Asn Asp Gin Pro Leu Thr Thr Gly Met Thr Gin Asp Ser lie 3265 3270 3275 3280
Asn Asn Tyr Glu Ala Lys Arg Asn Glu Ala Gin Ser Ala lie Arg Asn 3285 3290 3295
Ala Glu Ala Val lie Asn Asn Gly Asp Ala Thr Ala Lys Gin lie Ser .3300 3305 3310
Asp Glu Lys Ser Lys Val Glu Gin Ala Leu Ala His Leu Asn Asp Ala 3315 3320 3325
Lys Gin Gin Leu Thr Ala Asp Thr Thr Glu Leu Gin Thr Ala Val Gin 3330 3335 3340 ,
Gin Leu Asn Arg Arg Gly Asp Thr Asn Asn Lys Lys Pro Arg Ser lie 3345 3350 3355 3360
Asn Ala Tyr Asn Lys Ala He Gin Ser Leu Glu Thr Gin lie Thr Ser 3365 3370 3375
Ala Lys Asp Asn Ala Asn Ala Val lie Gin Lys Pro lie Arg Thr Val 3380 3385 3390 -33- 119629-序列表.doc 200815028
Gin Glu Val Asn Asn Ala Leu Gin Gin Val Asn Gin Leu Asn Gin Gin 3395 3400 3405
Leu Thr Glu Ala lie Asn Gin Leu Gin Pro Leu Ser Asn Asn Asp Ala 3410 3415 3420
Leu Lys Ala Ala Arg Leu Asn Leu Glu Asn Lys lie Asn Gin Thr Val 3425 3430 3435 3440
Gin Thr Asp Gly Met Thr Gin Gin Ser He Glu Ala Tyr Gin Asn Ala 3445 3450 3455
Lys Arg Val Ala Gin Asn Glu Ser Asn Thr Ala Leu Ala Leu He Asn 3460 3465 3470
Asn Gly Asp Ala Asp Glu Gin Gin lie Thr Thr Glu Thr Asp Arg Val 3475 3480 3485
Asn Gin Gin Thr Thr Asn Leu Thr Gin Ala lie Asn Gly Leu Thr Val 3490 3495 3500
Asn Lys Glu Pro Leu Glu Thr Ala Lys Thr Ala Leu Gin Asn Asn lie 3505 3510 3515 3520
Asp Gin Val Pro Ser Thr Asp Gly Met Thr Gin Gin Ser Val Ala Asn 3525 3530 3535
Tyr Asn Gin Lys Leu Gin lie Ala Lys Asn Glu lie Asn Thr He Asn 3540 3545 3550
Asn Val Leu Ala Asn Asn Pro Asp Val Asn Ala lie Lys Thr Asn Lys 3555 3560 3565
Ala Glu Ala Glu Arg lie Ser Asn Asp Leu Thr Gin Ala Lys Asn Asn 3570 3575 3580
Leu Gin Val Asp Thr Gin Pro Leu Glu Lys lie Lys Arg Gin Leu Gin 3585 3590 3595 3600
Asp Glu lie Asp Gin Gly Thr Asn Thr Asp Gly Met Thr Gin Asp Ser 3605 3610 3615
Val Asp Asn Tyr Asn Asp Ser Leu Ser Ala Ala lie He Glu Lys Gly 3620 3625 3630
Lys Val Asn Lys Leu Leu Lys Arg Asn Pro Thr Val Glu Gin Val Lys 3635 3640 3645
Glu Ser Val Ala Asn Ala Gin Gin Val lie Gin Asp Leu Gin Asn Ala 3650 3655 3660
Arg Thr Ser Leu Val Pro Asp Lys Thr Gin Leu Gin Glu Ala Lys Asn 3665 3670 3675 3680
Arg Leu Glu Asn Ser lie Asn Gin Gin Thr Asp Thr Asp Gly Met Thr 3685 3690 3695
Gin Asp Ser Leu Asn Asn Tyr Asn Asp Lys Leu Ala Lys Ala Arg Gin 3700 3705 3710
Asn Leu Glu Lys He Ser Lys Val Leu Gly Gly Gin Fro Thr Val Ala 3715 3720 3725
Glu lie Arg Gin Asn Thr Asp Glu Ala Asn Ala His Lys Gin Ala Leu 3730 3735 3740
Asp Thr Ala Arg Ser Gin Leu Thr Leu Asn Arg Glu Pro Tyr lie Asn 3745 3750 3755 3760
His lie Asn Asn Glu Ser His Leu Asn Asn Ala Gin Lys Asp Asn Phe 3765 3770 3775
Lys Ala Gin Val Asn Ser Ala Pro Asn His Asn Thr Leu Glu Thr He 3780 3785 3790
Lys Asn Lys Ala Asp Thr Leu Asn Gin Ser Met Thr Ala Leu Ser Glu 3795 3800 3805
Ser lie Ala Asp Tyr Glu Asn Gin Lys Gin Gin Glu Asn Tyr Leu Asp 3810 3815 3820
Ala Ser Asn Asn Lys Arg Gin Asp Tyr Asp Asn Ala Val Asn Ala Ala 3825 3830 3835 3840
Lys Gly He Leu Asn Gin Thr Gin Ser Pro Thr Met Ser Ala Asp Val 3845 3850 3855 lie Asp Gin Lys Ala Glu Asp Val Lys Arg Thr Lys Thr Ala Leu Asp 3860 3865 3870
Gly Asn Gin Arg Leu Glu Val Ala Lys Gin Gin Ala Leu Asn His Leu 3875 3880 3885
Asn Thr Leu Asn Asp Leu Asn Asp Ala Gin Arg Gin Thr Leu Thr Asp 3890 3895 3900
Thr lie Asn His Ser Pro Asn lie Asn Ser Val Asn Gin Ala Lys Glu 3905 3910 3915 3920
Lys Ala Asn Thr Val Asn Thr Ala Met Thr Gin Leu Lys Gin Thr lie 3925 3930 3935
Ala Asn Tyr Asp Asp Glu Leu His Asp Gly Asn Tyr He Asn Ala Asp 3940 3945 3950
Lys Asp Lys Lys Asp Ala Tyr Asn Asn Ala Val Asn Asn Ala Lys Gin 3955 3960 3965
Leu lie Asn Gin Ser Asp Ala Asn Gin Ala Gin Leu Asp Pro Ala Glu 3970 3975 3980 lie Asn Lys Val Thr Gin Arg Val Asn Thr Thr Lys Asn Asp Leu Asn 34- 119629-序列表.doc 200815028 3985 3990 3995 4000
Gly Asn Asp Lys Leu Ala Glu Ala Lys Arg Asp Ala Asn Thr Thr lie 4005 4010 4015
Asp Gly Leu Thr Tyr Leu Asn Glu Ala Gin Arg Asn Lys Ala Lys Glu 4020 4025 4030
Asn Val Gly Lys Ala Ser Thr Lys Thr Asn lie Thr Ser Gin Leu Gin 4035 4040 4045
Asp Tyr Asn Gin Leu Asn He Ala Met Gin Ala Leu Arg Asn Ser Val 4050 4055 4060
Asn Asp Val Asn Asn Val Lys Ala Asn Ser Asn Tyr lie Asn Glu Asp 4065 4070 4075 4080
Asn Gly Pro Lys Glu Ala Tyr Asn Gin Ala Val Thr His Ala Gin Thr 4085 4090 4095
Leu lie Asn Ala Gin Ser Asn Pro Glu Met Ser Arg Asp Val Val Asn 4100 4105 4110
Gin Lys Thr Gin Ala Val Asn Thr Ala His Gin Asn Leu His Gly Gin 4115 4120 4125
Gin Lys Leu Glu Gin Ala Gin Ser Ser Ala Asn Thr Glu lie Gly Asn 4130 4135 4140
Leu Pro Asn Leu Thr Asn Thr Gin Lys Ala Lys Glu Lys Glu Leu Val 4145 4150 4155 4160
Asn Ser Lys Gin Thr Arg Thr Glu Val Gin Glu Gin Leu Asn Gin Ala 4165 4170 4175
Lys Ser Leu Asp Ser Ser Met Gly Thr Leu Lys Ser Leu Val Ala Lys 4180 4185 4190
Gin Pro Thr Val Gin Lys Thr Ser Val Tyr He Asn Glu Asp Gin Pro 4195 4200 4205
Glu Gin Ser Ala Tyr Asn Asp Ser lie Thr Wet Gly Gin Thr lie lie 4210 4215 4220
Asn Lys Thr Ala Asp Pro Val Leu Asp Lys Thr Leu Val Asp Asn Ala 4225 4230 4235 4240 lie Ser Asn He Ser Thr Lys Glu Asn Ala Leu His Gly Glu Gin Lys 4245 4250 4255
Leu Thr Thr Ala Lys Thr Glu Ala lie Asn Ala Leu Asn Thr Leu Ala 4260 4265 4270
Asp Leu Asn Thr Pro Gin Lys Glu Ala lie Lys Thr Ala lie Asn Thr 4275 4280 4285
Ala His Thr Arg Thr Asp Val Thr Ala Glu Gin Ser Lys Ala Asn Gin 4290 4295 4300 lie Asn Ser Ala Met His Thr Leu Arg Gin Asn lie Ser Asp Asn Glu 4305 4310 4315 4320
Ser Val Thr Asn Glu Ser Asn Tyr lie Asn Ala Glu Pro Glu Lys Gin 4325 4330 4335
His Ala Phe Thr Glu Ala Leu Asn Asn Ala Lys Glu lie Val Asn Glu 4340 4345 4350
Gin Gin Ala Thr Leu Asp Ala Asn Ser lie Asn Gin Lys Ala Gin Ala 4355 4360 4365 lie Leu Thr Thr Lys Asn Ala Leu Asp Gly Glu Glu Gin Leu Arg Arg 4370 4375 4380
Ala Lys Glu Asn Ala Asp Gin Glu He Asn Thr Leu Asn Gin Leu Thr 4385 4390 4395 4400
Asp Ala Gin Arg Asn Ser Glu Lys Gly Leu Val Asn Ser Ser Gin Thr 4405 4410 4415
Arg Thr Glu Val Ala Ser Gin Leu Ala Lys Ala Lys Glu Leu Asn Lys 4420 4425 4430
Val Met Glu Gin Leu Asn His Leu lie Asn Gly Lys Asn Gin Met He 4435 4440 4445
Asn Ser Ser Lys Phe lie Asn Glu Asp Ala Asn Gin Gin Gin Ala Tyr 4450 4455 4460
Ser Asn Ala lie Ala Ser Ala Glu Ala Leu Lys Asn Lys Ser Gin Asn 4465 4470 4475 4480
Fro Glu Leu Asp Lys Val Thr lie Glu Gin Ala He Asn Asn lie Asn 4485 4490 4495
Ser Ala lie Asn Asn Leu Asn Gly Glu Ala Lys Leu Thr Lys Ala Lys 4500 4505 4510
Glu Asp Ala Val Ala Ser lie Asn Asn Leu Ser Gly Leu Thr Asn Glu 4515 4520 4525
Gin Lys Thr Lys Glu Asn Gin Ala Val Asn Gly Ala Gin Thr Arg Asp 4530 4535 4540
Gin Vai Ala Asn Lys Leu Arg Asp Ala Glu Ala Leu Asp Gin Ser Met 4545 4550 4555 4560
Gin Thr Leu Arg Asp Leu Val Asn Asn Gin Asn Ala He His Ser Thr 4565 4570 4575
Ser Asn Tyr Phe Asn Glu Asp Ser Thr Gin Lys Asn Thr Tyr Asp Asn 35- 119629-序列表.doc 200815028 4580 4585 4590
Ala He Asp Asn Gly Ser Thr Tyr lie Thr Gly Gin His Asn Pro Glu 4595 4600 4605
Leu Asn Lys Ser Thr He Asp Gin Thr lie Ser Arg lie Asn Thr Ala 4610 4615 4620
Lys Asn Asp Leu His Gly Val Glu Lys Leu Gin Arg Asp Lys Gly Thr 4625 4630 4635 4640
Ala Asn Gin Glu lie Gly Gin Leu Gly Tyr Leu Asn Asp Pro Gin Lys 4645 4650 4655
Ser Gly Glu Glu Ser Leu Val Asn Gly Ser Asn Thr Arg Ser Glu Val 4660 4665 4670
Glu Glu His Leu Asn Glu Ala Lys Ser Leu Asn Asn Ala Met Lys Gin 4675 4680 4685
Leu Arg Asp Lys Val Ala Glu Lys Thr Asn Val Lys Gin Ser Ser Asp 4690 4695 4700
Tyr lie Asn Asp Ser Thr Glu His Gin Arg Gly Tyr Asp Gin Ala Leu 4705 4710 4715 4720
Gin Glu Ala Glu Asn lie lie Asn Glu lie Gly Asn Pro Thr Leu Asn 4725 4730 4735
Lys Ser Glu lie Glu Gin Lys Leu Gin Gin Leu Thr Asp Ala Gin Asn 4740 4745 4750
Ala Leu Gin Gly Ser His Leu Leu Glu Glu Ala Lys Asn Asn Ala He 4755 4760 4765
Thr Gly He Asn Lys Leu Thr Ala Leu Asn Asp Ala Gin Arg Gin Lys 4770 4775 4780
Ala lie Glu Asn Val Gin Ala Gin Gin Thr lie Pro Ala Val Asn Gin 4785 4790 4795 4800
Gin Leu Thr Leu Asp Arg Glu lie Asn Thr Ala Met Gin Ala Leu Arg 4805 4810 4815
Asp Lys Val Gly Gin Gin Asn Asn Val His Gin Gin Ser Asn Tyr Phe 4820 4825 4830
Asn Glu Asp Glu Gin Pro Lys His Asn Tyr Asp Asn Ser Val Gin Ala 4835 4840 4845
Gly Gin Thr lie lie Asp Lys Leu Gin Asp Pro lie Met Asn Lys Asn 4850 4855 4860
Glu lie Glu Gin Ala lie Asn Gin lie Asn Thr Thr Gin Thr Ala Leu 4865 4870 4875 4880
Ser Gly Glu Asn Lys Leu His Thr Asp Gin Glu Ser Thr Asn Arg Gin 4885 4890 4895 lie Glu Gly Leu Ser Ser Leu Asn Thr Ala Gin lie Asn Ala Glu Lys 4900 4905 4910
Asp Leu Val Asn Gin Ala Lys Thr Arg Thr Asp Val Ala Gin Lys Leu 4915 4920 4925
Ala Ala Ala Lys Glu lie Asn Ser Ala Met Ser Asn Leu Arg Asp Gly 4930 4935 4940 lie Gin Asn Lys Glu Asp lie Lys Arg Ser Ser Ala Tyr lie Asn Ala 4945 4950 4955 4960
Asp Pro Thr Lys Val Thr Ala Tyr Asp Gin Ala Leu Gin Asn Ala Glu 4965 4970 4975
Asn lie lie Asn Ala Thr Pro Asn Val Glu Leu Asn Lys Ala Thr He 4980 4985 4990
Glu Gin Ala Leu Ser Arg Val Gin Gin Ala Gin Gin Asp Leu Asp Gly 4995 5000 5005
Val Gin Gin Leu Ala Asn Ala Lys Gin Gin Ala Thr Gin Thr Val Asn 5010 5015 5020
Gly Leu Asn Ser Leu Asn Asp Gly Gin Lys Arg Glu Leu Asn Leu Leu 5025 5030 5035 5040 lie Asn Ser Ala Asn Thr Arg Thr Lys Val Gin Glu Glu Leu Asn Lys 5045 5050 5055
Ala Thr Glu Leu Asn His Ala Met Glu Ala Leu Arg Asn Ser Val Gin 5060 5065 5070
Asn Val Asp Gin Val Lys Gin Ser Ser Asn Tyr Val Asn Glu Asp Gin 5075 5080 5085
Pro Glu Gin His Asn Tyr Asp Asn Ala Val Asn Glu Ala Gin Ala Thr 5090 5095 5100 lie Asn Asn Asn Ala Gin Pro Val Leu Asp Lys Leu Ala lie Glu Arg 5105 5110 5115 5120
Leu Thr Gin Thr Val Asn Thr Thr Lys Asp Ala Leu His Gly Ala Gin 5125 5130 5135
Lys Leu Thr Gin Asp Gin Gin Ala Ala Glu Thr Gly lie Arg Gly Leu 5140 5145 5150
Thr Ser Leu Asn Glu Pro Gin Lys Asn Ala Glu Val Ala Lys Val Thr 5155 5160 5165
Ala Ala Thr Thr Arg Asp Glu Val Arg Asn lie Arg Gin Glu Ala Thr 36· 119629·序列表.doc 200815028 5170 5175 5180
Thr Leu Asp Thr Ala Met Leu Gly Leu Arg Lys Ser lie Lys Asp Lys 5185 5190 5195 5200
Asn Asp Thr Lys Asn Ser Ser Lys Tyr lie Asn Glu Asp His Asp Gin 5205 5210 5215
Gin Gin Ala Tyr Asp Asn Ala Val Asn Asn Ala Gin Gin Val lie Asp 5220 5225 5230
Glu Thr Gin Ala Thr Leu Ser Ser Asp Thr lie Asn Gin Leu Ala Asn 5235 5240 5245
Ala Val Thr Gin Ala Lys Ser Asn Leu His Gly Asp Thr Lys Leu Gin 5250 5255 5260
His Asp Lys Asp Ser Ala Lys Gin Thr lie Ala Gin Leu Gin Asn Leu 5265 5270 5275 5280
Asn Ser Ala Gin Lys His Met Glu Asp Ser Leu He Asp Asn Glu Ser 5285 5290 5295
Thr Arg Thr Gin Val Gin His Asp Leu Thr Glu Ala Gin Ala Leu Asp 5300 5305 5310
Gly Leu Met Gly Ala Leu Lys Glu Ser lie Lys Asp Tyr Thr Asn lie 5315 5320 5325
Val Ser Asn Gly Asn Tyr lie Asn Ala Glu Pro Ser Lys Lys Gin Ala 5330 5335 5340
Tyr Asp Ala Ala Val Gin Asn Ala Gin Asn lie lie Asn Gly Thr Asn 5345 5350 5355 5360
Gin Pro Thr lie Asn Lys Gly Asn Val Thr Thr Ala Thr Gin Thr Val 5365 5370 5375
Lys Asn Thr Lys Asp Ala Leu Asp Gly Asp His Arg Leu Gly Glu Ala 5380 5385 5390
Lys Asn Asn Ala Asn Gin Thr lie Arg Asn Leu Ser Asn Leu Asn Asn 5395 5400 5405
Ala Gin Lys Asp Ala Glu Lys Asn Leu Val Asn Ser Ala Ser Thr Leu 5410 5415 5420
Glu Gin Val Gin Gin Asn Leu Gin Thr Ala Gin Gin Leu Asp Asn Ala 5425 5430 5435 5440
Met Gly Glu Leu Arg Gin Ser lie Ala Lys Lys Asp Gin Val Lys Ala 5445 5450 5455
Asp Ser Lys Tyr Leu Asn Glu Asp Pro Gin lie Lys Gin Asn Tyr Asp 5460 5465 5470
Asp Ala Val Gin Arg Val Glu Thr lie lie Asn Glu Thr Gin Asn Pro 5475 5480 5485
Glu Leu Leu Lys Ala Asn lie Asp Gin Ala Thr Gin Ser Val Gin Asn 5490 5495 5500
Ala Glu Gin Ala Leu His Gly Ala Glu Lys Leu Asn Gin Asp Lys Gin 5505 5510 5515 5520
Thr Ser Ser Thr Glu Leu Asp Gly Leu Thr Asp Leu Thr Asp Ala Gin 5525 5530 5535
Arg Glu Lys Leu Arg Glu Gin He Asn Thr Ser Asn Ser Arg Asp Asp 5540 5545 5550 lie Lys Gin Lys lie Glu Gin Ala Lys Ala Leu Asn Asp Ala Met Lys 5555 5560 5565
Lys Leu Lys Glu Gin Val Ala Gin Lys Asp Gly Val His Ala Asn Ser 5570 5575 5580
Asp Tyr Thr Asn Glu Asp Ser Ala Gin Lys Asp Ala Tyr Asn Asn Ala 5585 5590 5595 5600
Leu Lys Gin Ala Glu Asp lie lie Asn Asn Ser Ser Asn Pro Asn Leu 5605 5610 5615
Asn Ala Gin Asp lie Thr Asn Ala Leu Asn Asn lie Lys Gin Ala Gin 5620 5625 5630
Asp Asn Leu His Gly Ala Gin Lys Leu Gin Gin Asp Lys Asn Thr Thr 5635 5640 5645
Asn Gin Ala lie Gly Asn Leu Asn His Leu Asn Gin Pro Gin Lys Asp 5650 5655 5660
Ala Leu lie Gin Ala lie Asn Gly Ala Thr Ser Arg Asp Gin Val Ala 5665 5670 5675 5680
Glu Lys Leu Lys Glu Ala Glu Ala Leu Asp Glu Ala Met Lys Gin Leu 5685 5690 5695
Glu Asp Gin Val Asn Gin Asp Asp Gin lie Ser Asn Ser Ser Pro Phe 5700 5705 5710 lie Asn Glu Asp Ser Asp Lys Gin Lys Thr Tyr Asn Asp Lys lie Gin 5715 5720 5725
Ala Ala Lys Glu lie lie Asn Gin Thr Ser Asn Pro Thr Leu Asp Lys 5730 5735 5740
Gin Lys He Ala Asp Thr Leu Gin Asn lie Lys Asp Ala Val Asn Asn 5745 5750 5755 5760
Leu His Gly Asp Gin Lys Leu Ala Gin Ser Lys Gin Asp Ala Asn Asn 5765 5770 5775 •37- 119629-序列表.doc 200815028
Gin Leu Asn His Leu Asp Asp Leu Thr Glu Glu Gin Lys Asn His Phe 5780 5785 5790
Lys Pro Leu lie Asn Asn Ala Asp Thr Arg Asp Glu Val Asn Lys Gin 5795 5800 5805
Leu Glu lie Ala Lys Gin Leu Asn Gly Asp Met Ser Thr Lee His Lys 5810 5815 5820
Val lie Asn Asp Lys Asp Gin lie Gin His Leu Ser Asn Tyr lie Asn 5825 5830 5835 5840
Ala Asp Asn Asp Lys Lys Gin Asn Tyr Asp Asn Ala lie Lys Glu Ala 5845 5850 5855
Glu Asp Leu lie His Asn His Pro Asp Thr Leu Asp His Lys Ala Leu 5860 5865 5870
Gin Asp Leu Leu Asn Lys lie Asp Gin Ala His Asn Glu Leu Asn Gly 5875 5880 5885
Glu Ser Arg Phe Lys Gin Ala Leu Asp Asn Ala Leu Asn Asp lie Asp 5890 5895 5900
Ser Leu Asn Ser Leu Asn Val Pro Gin Arg Gin Thr Val Lys Asp Asn 5905 5910 5915 5920
He Asn His Val Thr Thr Leu Glu Ser Leu Ala Gin Glu Leu Gin Lys 5925 5930 5935
Ala Lys Glu Leu Asn Asp Ala Met Lys Ala Met Arg Asp Ser He Met 5940 5945 5950
Asn Gin Glu Gin lie Arg Lys Asn Ser Asn Tyr Thr Asn Glu Asp Leu 5955 5960 5965
Ala Gin Gin Asn Ala Tyr Asn His Ala Val Asp Lys lie Asn Asn He 5970 5975 5980 lie Gly Glu Asp Asn Ala Thr Met Asp Pro Gin lie lie Lys Gin Ala
5985 5990 5995 6000
Thr Gin Asp lie Asn Thr Ala lie Asn Gly Leu Asn Gly Asp Gin Lys 6005 6010 6015
Leu Gin Asp Ala Lys Thr Asp Ala Lys Gin Gin lie Thr Asn Phe Thr 6020 6025 6030
Gly Leu Thr Glu Pro Gin Lys Gin Ala Leu Glu Asn He lie Asn Gin 6035 6040 6045
Gin Thr Ser Arg Ala Asn Val Ala Lys Gin Leu Ser His Ala Lys Phe 6050 6055 6060
Leu Asn Gly Lys Met Glu Glu Leu Lys Val Ala Val Ala Lys Ala Ser 6065 6070 6075 6080
Leu Val Arg Gin Asn Ser Asn Tyr lie Asn Glu Asp Val Ser Glu Lys 6085 6090 6095
Glu Ala Tyr Glu Gin Ala lie Ala Lys Gly Gin Glu lie lie Asn Ser 6100 6105 6110
Glu Asn Asn Pro Thr lie Ser Ser Thr Asp He Asn Arg Thr lie Gin 6115 6120 6125
Glu lie Asn Asp Ala Glu Gin Asn Leu His Gly Asp Asn Lys Leu Arg 6130 6135 6140
Gin Ala Gin Glu lie Ala Lys Asn Glu He Gin Asn Leu Asp Gly Leu 6145 6150 6155 6160
Asn Ser Ala Gin He Thr Lys Leu lie Gin Asp lie Gly Arg Thr Thr 6165 6170 6175
Thr Lys Pro Ala Val Thr Gin Lys Leu Glu Glu Ala Lys Ala He Asn 6180 6185 6190
Gin Ala Met Gin Gin Leu Lys Gin Ser lie Ala Asp Lys Asp Ala Thr 6195 6200 6205
Leu Asn Ser Ser Asn Tyr Leu Asn Glu Asp Ser Glu Lys Lys Leu Ala 6210 6215 6220
Tyr Asp Asn Ala Val Ser Gin Ala Glu Gin Leu He Asn Gin Leu Asn 6225 6230 6235 6240
Asp Pro Thr Met Asp lie Ser Asn lie Gin Ala lie Thr Gin Lys Val 6245 6250 6255
He Gin Ala Lys Asp Ser Leu His Gly Ala Asn Lys Leu Ala Gin Asn 6260 6265 6270
Gin Ala Asp Ser Asn Leu lie lie Asn Gin Ser Thr Asn Leu Asn Asp 6275 6280 6285
Lys Gin Lys Gin Ala Leu Asn Asp Leu lie Asn His Ala Gin Thr Lys 6290 6295 6300
Gin Gin Val Ala Glu lie He Ala Gin Ala Asn Lys Leu Asn Asn Glu 6305 6310 6315 6320
Met Gly Thr Leu Lys Thr Leu Val Glu Glu Gin Ser Asn Val His Gin 6325 6330 6335
Gin Ser Lys Tyr lie Asn Glu Asp Pro Gin Val Gin Asn lie Tyr Asn 6340 6345 6350
Asp Ser lie Gin Lys Gly Arg Glu lie Leu Asn Gly Thr Thr Asp Asp 6355 6360 6365
Val Leu Asn Asn Asn Lys lie Ala Asp Ala lie Gin Asn lie His Leu 38- 119629-序列表.doc 200815028 6370 6375 6380
Thr Lys Asn Asp Leu His Gly Asp Gin Lys Leu Gin Lys Ala Gin Gin 6385 6390 6395 6400
Asp Ala Thr Asn GIu Leu Asn Tyr Leu Thr Asn Leu Asn Asn Ser Gin 6405 6410 6415
Arg Gin Ser Glu His Asp Glu lie Asn Ser Ala Pro Ser Arg Thr Glu 6420 6425 6430
Val Ser Asn Asp Leu Asn His Ala Lys Ala Leu Asn Glu Ala Met Arg 6435 6440 6445
Gin Leu Glu Asn Glu Val Ala Leu GIu Asn Ser Val Lys Lys Leu Ser 6450 6455 6460
Asp Phe He Asn Glu Asp Glu Ala Ala Gin Asn Glu Tyr Ser Asn Ala 6465 6470 6475 6480
Leu Gin Lys Ala Lys Asp lie lie Asn Gly Val Pro Ser Ser Thr Leu 6485 6490 6495
Asp Lys Ala Thr lie Glu Asp Ala Leu Leu Glu Leu Gin Asn Ala Arg 6500 6505 6510
Glu Ser leu His Gly Glu Gin Lys Leu Gin Glu Ala Lys Asn Gin Ala 6515 6520 6525
Val Ala Glu lie Asp Asn Leu Gin Ala Leu Asn Pro Gly Gin Val Leu 6530 6535 6540
Ala Glu Lys Thr Leu Val Asn Gin Ala Ser Thr Lys Pro Glu Val Gin 6545 6550 6555 6560
Glu Ala Leu Gin Lys Ala Lys Glu Leu Asn Glu Ala Met Lys Ala Leu 6565 6570 6575
Lys Thr Glu He Asn Lys Lys Glu Gin lie Lys Ala Asp Ser Arg Tyr 6580 6585 6590
Val Asn Ala Asp Ser Gly Leu Gin Ala Asn Tyr Asn Ser Ala Leu Asn 6595 6600 6605
Tyr Gly Ser Gin He lie Ala Thr Thr Gin Pro Pro Glu Leu Asn Lys 6610 6615 6620
Asp Val lie Asn Arg Ala Thr Gin Thr lie Lys Thr Ala Glu Asn Asn 6625 6630 6635 6640
Leu Asn Gly Gin Ser Lys Leu ALa Glu Ala Lys Ser Asp Gly Asn Gin 6645 6650 6655
Ser He Glu His Leu Gin Giy Leu Thr Gin Ser Gin Lys Asp Lys Gin 6660 6665 6670
His Asp Leu lie Asn Gin Ala Gin Thr Lys Gin Gin Val Asp Asp lie 6675 6680 6685
Val Asn Asn Ser Lys Gin Leu Asp Asn Ser Met Asn Gin Leu Gin Gin 6690 6695 6700 lie Val Asn Asn Asp Asn Thr Val Lys Gin Asn Ser Asp Phe He Asn 6705 6710 6715 6720
Glu Asp Ser Ser Gin Gin Asp Ala Tyr Asn His Ala lie Gin Ala Ala 6725 6730 6735
Lys Asp Leu lie Thr Ala His Pro Thr lie Met Asp Lys Asn Gin lie 6740 6745 6750
Asp Gin Ala lie Glu Asn lie Lys Gin Ala Leu Asn Asp Leu His Gly 6755 6760 6765
Ser Asn Lys Leu Ser Glu Asp Lys Lys Glu Ala Ser Glu Gin Leu Gin 6770 6775 6780
Asn Leu Asn Ser Leu Thr Asn Gly Gin Lys Asp Thr lie Leu Asn His 6785 6790 6795 6800
He Phe Ser Ala Pro Thr Arg Ser Gin Val Gly Glu Lys He Ala Ser 6805 6810 6815
Ala Lys Gin Leu Asn Asn Thr Met Lys Ala Leu Arg Asp Ser He Ala 6820 6825 6830
Asp Asn Asn Glu He Leu Gin Ser Ser Lys Tyr Phe Asn Glu Asp Ser 6835 6840 6845
Glu Gin Gin Asn Ala Tyr Asn Gin Ala Val Asn Lys Ala Lys Asn lie 6850 6855 6860
He Asn Asp Gin Pro Thr Pro Val Met Ala Asn Asp Glu He Gin Ser 6865 6870 6875 6880
Val Leu Asn Glu Val Lys Gin Thr Lys Asp Asn Leu His Gly Asp Gin 6885 6890 6895
Lys Leu Ala Asn Asp Lys Thr Asp Ala Gin Ala Thr Leu Asn Ala Leu 6900 6905 6910
Asn Tyr Leu Asn Gin Ala Gin Arg Gly Asn Leu Glu Thr Lys Val Gin 6915 6920 6925
Asn Ser Asn Ser Arg Pro Glu Val Gin Lys Val Val Gin Leu Ala Asn 6930 6935 6940
Gin Leu Asn Asp Ala Met Lys Lys Leu Asp Asp Ala Leu Thr Gly Asn 6945 6950 6955 6960
Asp Ala lie Lys Gin Thr Ser Asn Tyr lie Asn Glu Asp Thr Ser Gin 6965 6970 6975 -39- 119629-序列表.doc 200815028
Gin Val Asn Phe Asp Glu Tyr Thr Asp Arg Gly Lys Asn lie Val Ala 6980 6985 6990
Glu Gin Thr Asn Pro Asn Met Ser Pro Thr Asn He Asn Thr lie Ala 6995 7000 7005
Asp Lys lie Thr Glu Ala Lys Asn Asp Leu His Gly Val Gin Lys Leu 7010 7015 7020
Lys Gin Ala Gin Girl Gin Ser lie Asn Thr He Asn Gin Met Thr Gly 7025 7030 7035 7040
Leu Asn Gin Ala Gin Lys Glu Gin Leu Asn Gin Glu lie Gin Gin Thr 7045 7050 7055
Gin Thr Arg Ser Glu Val His Gin Val lie Asn Lys Ala GIo Ala Leu 7060 7065 7070
Asn Asp Ser Met Asn Thr Leu Arg Gin Ser lie Thr Asp Glu His Glu 7075 7080 7085
Val Lys Gin Thr Ser Asn Tyr He Asn Glu Thr Val Gly Asn Gin Thr 7090 7095 7100
Ala Tyr Asn Asn Ala Val Asp Arg Val Lys Gin He lie Asn Gin Thr 7105 7110 7115 7120
Ser Asn Pro Thr Met Asn Pro Leu Glu Val Glu Arg Ala Thr Ser Asn 7125 7130 7135
Val Lys lie Ser Lys Asp Ala Leu His Gly Glu Arg Glu Leu Asn Asp 7140 7145 7150
Asn Lys Asn Ser Lys Thr Fhe Ala Val Asn His Leu Asp Asn Leu Asn 7155 7160 7165
Gin Ala Gin Lys Glu Ala Leu Thr His Glu lie Glu Gin Ala Thr He 7170 7175 7180
Val Ser Gin Val Asn Asn lie Tyr Asn Lys Ala Lys Ala Leu Asn Asn
7185 7190 7195 7200
Asp Met Lys Lys Leu Lys Asp He Val Ala Gin Gin Asp Asn Val Arg 7205 7210 7215
Gin Ser Asn Asn Tyr lie Asn Glu Asp Ser Thr Pro Gin Asn Met Tyr 7220 7225 7230
Asn Asp Thr lie Asn His Ala Gin Ser lie lie Asp Gin Val Ala Asn 7235 7240 7245
Pro Thr Met Ser His Asp Glu lie Glu Asn Ala He Asn Asn He Lys 7250 7255 7260
His Ala lie Asn Ala Leu Asp Gly Glu His Lys Leu Gin Gin Ala Lys 7265 7270 7275 7280
Glu Asn Ala Asn Leu Leu lie Asn Ser Leu Asn Asp Leu Asn Ala Pro 7285 7290 7295
Gin Arg Asp Ala lie Asn Arg Leu Val Asn Glu Ala Gin Thr Arg Glu 7300 7305 7310
Lys Val Ala Glu Gin Leu Gin Ser Ala Gin Ala Leu Asn Asp Ala Met 7315 7320 7325
Lys His Leu Arg Asn Ser lie Gin Asn Gin Ser Ser Val Arg Gin Glu 7330 7335 7340
Ser Lys Tyr lie Asn Ala Ser Asp Ala Lys Lys Glu Gin Tyr Asn His 7345 7350 7355 7360
Ala Val Arg Glu Val Glu Asn lie lie Asn Glu Gin His Pro Thr Leu 7365 7370 7375
Asp Lys Glu lie He Lys Gin Leu Thr Asp Gly Val Asn Gin Ala Asn 7380 7385 7390
Asn Asp Leu Asn Gly Val Glu Leu Leu Asp Ala Asp Lys Gin Asn Ala 7395 7400 7405
His Gin Ser He Pro Thr Leu Met His Leu Asn Gin Ala Gin Gin Asn 7410 7415 7420
Ala Leu Asn Glu Lys He Asn Asn Ala Val Thr Arg Thr Glu Val Ala 7425 7430 7435 7440
Ala lie He Gly Gin Ala Lys Leu Leu Asp His Ala Met Glu Asn Leu 7445 7450 7455
Glu Glu Ser He Lys Asp Lys Glu Gin Val Lys Gin Ser Ser Asn Tyr 7460 7465 7470 lie Asn Glu Asp Ser Asp Val Gin Glu Thr Tyr Asp Asn Ala Val Asp 7475 7480 7485
His Val Thr Glu lie Leu Asn Gin Thr Val Asn Pro Thr Leu Ser lie 7490 7495 7500
Glu Asp He Glu His Ala He Asn Glu Val Asn Gin Ala Lys Lys Gin 7505 7510 7515 7520
Leu Arg Gly Lys Gin Lys Leu Tyr Gin Thr lie Asp Leu Ala Asp Lys 7525 7530 7535
Glu Leu Ser Lys Leu Asp Asp Leu Thr Ser Gin Gin Ser Ser Ser lie 7540 7545 7550
Ser Asn Gin lie Tyr Thr Ala Lys Thr Arg Thr Glu Val Ala Gin Ala 7555 7560 7565
He Glu Lys Ala Lys Ser Leu Asn His Ala Met Lys Ala Leu Asn Lys 40- 119629-序列表.doc 200815028 7570 7575 7580
Val Tyr Lys Asn Ala Asp Lys Val Leu Asp Ser Ser Arg Phe lie Asn 7585 7590 7595 7600
Glu Asp Gin Pro Glu Lys Lys Ala Tyr Gin Gin Ala lie Asn His Val 7605 7610 7615
Asp Ser lie lie His Arg Gin Thr Asn Fro Glu Met Asp Pro Thr Val 7620 7625 7630
He Asn Ser lie Thr His Glu Leu Glu Thr Ala Gin Asn Asn Leu His 7635 7640 7645
Gly Asp Gin Lys Leu Ala His Ala Gin Gin Asp Ala Ala Asn Val He 7650 7655 7660
Asn Gly Leu lie His Leu Asn Val Ala Gin Arg Glu Val Met lie Asn 7665 7670 7675 7680
Thr Asn Thr Asn Ala Thr Thr Arg Giu Lys Val Ala Lys Asn Leu Asp 7685 7690 7695
Asn Ala Gin Ala Leu Asp Lys Ala Met Glu Thr Leu Gin Gin Val Val 7700 7705 7710
Ala His Lys Asn Asn lie Leu Asn Asp Ser Lys Tyr Leu Asn Glu Asp 7715 7720 7725
Ser Lys Tyr Gin Gin Gin Tyr Asp Arg Val He Ala Asp Ala Glu Gin 7730 7735 7740
Leu Leu Asn Gin Thr Thr Asn Pro Thr Leu Glu Pro Tyr Lys Val Asp 7745 7750 7755 7760 lie Val Lys Asp Asn Val Leu Ala Asn Glu Lys lie Leu Phe Gly Ala 7765 7770 7775
Glu Lys Leu Ser Tyr Asp Lys Ser Asn Ala Asn Asp Glu lie Lys His 7780 7785 7790
Met Asn Tyr Leu Asn Asn Ala Gin Lys Gin Ser He Lys Asp Met lie 7795 7800 7805
Ser His Ala Ala Leu Arg Thr Glu Val Lys Gin Leu Leu Gin Gin Ala 7810 7815 7820
Lys He Leu Asp Glu Ala Met Lys Ser Leu Glu Asp Lys Thr Gin Val 7825 7830 7835 7840
Val lie Thr Asp Thr Thr Leu Pro Asn Tyr Thr Glu Ala Ser Glu Asp 7845 7850 7855
Lys Lys Glu Lys Val Asp Gin Thr Val Ser His Ala Gin Ala lie lie 7860 7865 7870
Asp Lys lie Asn Gly Ser Asn Val Ser Leu Asp Gin Val Arg Gin Ala 7875 7880 7885
Leu Glu Gin Leu Thr Gin Ala Ser Glu Asn Leu Asp Gly Asp Gin Arg 7890 7895 7900
Val Glu Glu Ala Lys Val His Ala Asn Gin Thr lie Asp Gin Leu Thr 7905 7910 7915 7920
His Leu Asn Ser Leu Gin Gin Gin Thr Ala Lys Glu Ser Val Lys Asn 7925 7930 7935
Ala Thr Lys Leu Glu Glu lie Ala Thr Val Ser Asn Asn Ala Gin Ala 7940 7945 7950
Leu Asn Lys Val Met Gly Lys Leu Glu Gin Phe lie Asn His Ala Asp 7955 7960 7965
Ser Val Glu Asn Ser Asp Asn Tyr Arg Gin Ala Asp Asp Asp Lys lie 7970 7975 7980 lie Ala Tyr Asp Glu Ala Leu Glu His Gly Gin Asp lie Gin Lys Thr 7985 7990 7995 8000
Asn Ala Thr Gin Asn Glu Thr Lys Gin Ala Leu Gin Gin Leu lie Tyr 8005 8010 8015
Ala Glu Thr Ser Leu Asn Gly Phe Glu Arg Leu Asn His Ala Arg Pro 8020 8025 8030
Arg Ala Leu Glu Tyr lie Lys Ser Leu Glu Lys lie Asn Asn Ala Gin 8035 8040 8045
Lys Ser Ala Leu Glu Asp Lys Val Thr Gin Ser His Asp Leu Leu Glu 8050 8055 8060
Leu Glu His lie Val Asn Glu Gly Thr Asn Leu Asn Asp lie Met Gly 8065 8070 8075 8080
Glu Leu Ala Asn Ala lie Val Asn Asn Tyr Ala Pro Thr Lys Ala Ser 8085 8090 8095 lie Asn Tyr lie Asn Ala Asp Asn Leu Arg Lys Asp Asn Phe Thr Gin 8100 8105 8110
Ala lie Asn Asn Ala Arg Asp Ala Leu Asn Lys Thr Gin Gly Gin Asn 8115 8120 8125
Leu Asp Phe Asn Ala He Asp Thr Phe Lys Asp Asp He Phe Lys Thr 8130 8135 8140
Lys Asp Ala Leu Asn Gly He Glu Arg Leu Thr Ala Ala Lys Ser Lys 8145 8150 8155 8160
Ala Glu Lys Leu He Asp Ser Leu Lys Phe lie Asn Lys Ala Gin Phe 8165 8170 8175 -41 - 119629-序列表.doc 200815028
Thr His Ala Asn Asp Glu lie Met Asn Thr Asn Ser lie Ala Gin Leu 8180 8185 8190
Ser Arg lie Val Asn Gin Ala Phe Asp Leu Asn Asp Ala Met Lys Ser 8195 8200 8205
Leu Arg Asp Glu Leu Asn Asn Gin Ala Phe Pro Val Gin Ala Ser Ser 8210 8215 8220
Asn Tyr lie Asn Ser Asp Glu Asp Leu Lys Gin Gin Phe Asp His Ala 8225 8230 8235 8240
Leu Ser Asn Ala Arg Lys Val Leu Ala Lys Glu Asn Gly Lys Asn Leu 8245 8250 8255
Asp Glu Lys Gin lie Gin Gly Leu Lys Gin Val lie Glu Asp Thr Lys 8260 8265 8270
Asp Ala Leu Asn Gly He Gin Arg Leu Ser Lys Ala Lys Ala Lys Ala 8275 8280 8285 lie Gin Tyr Val Gin Ser Leu Ser Tyr lie Asn Asp Ala Gin Arg His 8290 8295 8300 lie Ala Glu Asn Asn He His Asn Ser Asp Asp Leu Ser Ser Leu Ala 8305 8310 8315 8320
Asn Thr Leu Ser Lys Ala Ser Asp Leu Asp Asn Ala Met Lys Asp Leu 8325 8330 8335
Arg Asp Thr He Glu Ser Asn Ser Thr Ser Val Fro Asn Ser Val Asn 8340 8345 8350
Tyr lie Asn Ala Asp Lys Asn Leu Gin lie Glu Phe Asp Glu Ala Leu 8355 8360 8365
Gin Gin Ala Ser Ala Thr Ser Ser Lys Thr Ser Glu Asn Pro Ala Thr 8370 8375 8380
lie Glu Glu Val Leu Gly Leu Ser Gin Ala He Tyr Asp Thr Lys Asn 8385 8390 8395 8400
Ala Leu Asn Gly Glu Gin Arg Leu Ala Thr Glu Lys Ser Lys Asp Leu 8405 8410 8415
Lys Leu lie Lys Gly Leu Lys Asp Leu Asn Lys Ala Gin Leu Glu Asp 8420 8425 8430
Val Thr Asn Lys Val Asn Ser Ala Asn Thr Leu Thr Glu Leu Ser Gin 8435 8440 8445
Leu Thr Gin Ser Thr Leu Glu Leu Asn Asp Lys Met Lys Leu Leu Arg 8450 8455 8460
Asp Lys Leu Lys Thr Leu Val Asn Pro Val Lys Ala Ser Leu Asn Tyr 8465 8470 8475 8480
Arg Asn Ala Asp Tyr Asn Leu Lys Arg Gin Phe Asn Lys Ala Leu Lys 8485 8490 8495
Giu Ala Lys Gly Val Leu Asn Lys Asn Ser Gly Thr Asn Val Asn lie 8500 8505 8510
Asn Asp lie Gin His Leu Leu Thr Gin lie Asp Asn Ala Lys Asp Gin 8515 8520 8525
Leu Asn Gly Glu Arg Arg Leu Lys Glu His Gin Gin Lys Ser Glu Val 8530 8535 8540
Phe lie lie Lys Glu Leu Asp lie Leu Asn Asn Ala Gin Lys Ala Ala 8545 8550 8555 8560 lie lie Asn Gin lie Arg Ala Ser Lys Asp lie Lys lie He Asn Gin 8565 8570 8575 lie Val Asp Asn Ala He Glii Leu Asn Asp Ala Met Gin Gly Leu Lys 8580 8585 8590
Glu His Val Ala Gin Leu Thr Ala Thr Thr Lys Asp Asn lie Glu Tyr 8595 8600 8605
Leu Asn Ala Asp Glu Asp His Lys Leu Gin Tyr Asp Tyr Ala He Asn 8610 8615 8620
Leu Ala Asn Asn Val Leu Asp Lys Glu Asn Gly Thr Asn Lys Asp Ala 8625 8630 8635 8640
Asn He lie lie Gly Met He Gin Asn Met Asp Asp Ala Arg Ala Leu 8645 8650 8655
Leu Asn Gly lie Glu Arg Leu Lys Asp Ala Gin Thr Lys Ala His Asn 8660 8665 8670
Asp lie Lys Asp Thr Leu Lys Arg Gin Leu Asp Glu lie Glu His Ala 8675 8680 8685
Asn Ala Thr Ser Asn Ser Lys Ala Gin Ala Lys Gin Met Val Asn Glu 8690 8695 8700
Glu Ala Arg Lys Ala Leu Ser Asn lie Asn Asp Ala Thr Ser Asn Asp 8705 8710 8715 8720
Leu Val Asn Gin Ala Lys Asp Glu Gly Gin Ser Ala lie Glu His lie 8725 8730 8735
His Ala Asp Glu Leu Fro Lys Ala Lys Leu Asp Ala Asn Gin Met lie 8740 8745 8750
Asp Gin Lys Val Glu Asp lie ksn His Leu He Ser Gin Asn Pro Asn 8755 8760 8765 -42- 119629-序列表.doc 200815028
Leu Ser Asn Glu Glu Lys Asn Lys Leu lie Ser Gin lie Asn Lys Leu 8770 8775 8780
Val Asn Gly lie Lys Asn Glu He Gin Gin Ala lie Asn Lys Gin Gin 8785 8790 8795 8800
He Glu Asn Ala Thr Thr Lys Leu Asp Glu Val He Glu Thr Thr Lys 8805 8810 8815
Lys Leu lie He Ala Lys Ala Glu Ala Lys Gin Met lie Lys Glu Leu 8820 8825 8830
Ser Gin Lys Lys Arg Asp Ala lie Asn Asn Asn Thr Asp Leu Thr Pro 8835 8840 8845
Ser Gin Lys Ala His Ala Leu Ala Asp He Asp Lys Thr Glu Lys Asp 8850 8855 8860
Ala Leu Gin His lie Glu Asn Ser Asn Ser lie Asp Asp lie Asn Asn 8865 8870 8875 8880
Asn Lys Glu His Ala Phe Asn Thr Leu Ala His lie lie lie Trp Asp 8885 8890 8895
Thr Asp Gin Gin Pro Leu Val Phe Glu Leu Pro Glu Leu Ser Leu Gin 8900 8905 8910
Asn Ala Leu Val Thr Ser Glu Val Val Val His Arg Asp Glu Thr lie 8915 8920 8925
Ser Leu Glu Ser lie lie Gly Ala Met Thr Leu Thr Asp Glu Leu Lys 8930 8935 8940
Val Asn lie Val Ser Leu Pro Asn Thr Asp Lys Val Ala Asp His Leu 8945 8950 8955 8960
Thr Ala Lys Val Lys Val He Leu Ala Asp Gly Ser Tyr Val Thr Val 8965 8970 8975
Asn Val Pro Val Lys Val Val Glu Lys Glu Leu Gin lie Ala Lys Lys 8980 8985 8990
Asp Ala lie Lys Thr lie Asp Val Leu Val Lys Gin Lys lie Lys Asp 8995 9000 9005 lie Asp Ser Asn Asn Glu Leu Thr Ser Thr Gin Arg Glu Asp Ala Lys 9010 9015 9020
Ala Glu lie Glu Arg Leu Lys Lys Gin Ala lie Asp Lys Val Asn His 9025 9030 9035 9040
Ser Lys Ser lie Lys Asp lie Glu Thr Val Lys Arg Thr Asp Phe Glu 9045 9050 9055
Glu lie Asp Gin Phe Asp Pro Lys Arg Phe Thr Leu Asn Lys Ala Lys 9060 9065 9070
Lys Asp lie lie Thr Asp Val Asn Thr Gin He Gin Asn Gly Phe Lys 9075 9080 9085
Glu lie Glu Thr lie Lys Gly Leu Thr Ser Asn Glu Lys Thr Gin Phe 9090 9095 9100
Asp Lys Gin Leu Thr Ala Leu Gin Lys Glu Phe Leu Glu Lys Val Glu 9105 9110 9115 9120
His Ala His Asn Leu Val Glu Leu Asn Gin Leu Gin Gin Glu Phe Asn 9125 9130 9135
Asn Arg Tyr Lys His lie Leu Asn Gin Ala His Leu Leu Gly Glu Lys 9140 9145 9150
His lie Ala Glu His Lys Leu Gly Tyr Val Val Val Asn Lys Thr Gin 9155 9160 9165
Gin lie Leu Asn Asn Gin Ser Ala Ser Tyr Phe lie Lys Gin Trp Ala 9170 9175 9180
Leu Asp Arg lie Lys Gin lie Gin Leu Glu Thr Met Asn Ser lie Arg 9185 9190 9195 9200
Gly Ala His Thr Val Gin Asp Val His Lys Ala Leu Leu Gin Gly lie 9205 9210 9215
Glu Gin lie Leu Lys Val Asn Val Ser lie lie Asn Gin Ser Phe Asn 9220 9225 9230
Asp Ser Leu His Asn Phe Asn Tyr Leu His Ser Lys Phe Asp Ala Arg 9235 9240 9245
Leu Arg Glu Lys Asp Val Ala Asn His lie Val Gin Thr Glu Thr Phe 9250 9255 9260
Lys Glu Val Leu Lys Gly Thr Gly Val Glu Pro Gly Lys lie Asn Lys 9265 9270 9275 9280
Glu Thr Gin Gin Pro Lys Leu His Lys Asn Asp Asn Asp Ser Leu Phe 9285 9290 9295
Lys His Leu Val Asp Asn Phe Gly Lys Thr Val Gly Val lie Thr Leu 9300 9305 9310 丁hr Gly Leu leu Ser Ser Phe Trp Leu Val Leu Ala Lys Arg Arg Lys 9315 9320 9325
Lys Glu Glu Glu Glu Lys Gin Ser lie Lys Asn His His Lys Asp lie 9330 9335 9340
Arg Leu Ser Asp Thr Asp Lys lie Asp Pro lie Val lie Thr Lys Arg 9345 9350 9355 9360 43 119629-序列表.doc 200815028
Lys lie Asp Lys Glu Glu Gin lie Gin Asn Asp Asp Lys His Ser lie 9365 9370 9375
Pro Val Ala Lys His Lys Lys Ser Lys Glu Lys Gin Leu Ser Glu Glu 9380 9385 9390
Asp lie His Ser He Pro Val Val Lys Arg Lys Gin Asn Ser Asp Asn 9395 9400 9405
Lys Asp Thr Lys Gin Lys Lys Val Thr Ser Lys Lys Lys Lys Thr Pro 9410 9415 9420
Gin Ser Thr Lys Lys Val Val Lys Thr Lys Lys Arg Ser Lys Lys 9425 9430 9435 <210〉 16 <21!> 1115 <212〉 PRT <213〉葡萄球菌 <400〉 16
Met Arg Asp Lys Lys Gly Pro Val Asn Lys Arg Val Asp Phe Leu Ser 15 10 15
Asn Lys Leu Asn Lys Tyr Ser lie Arg Lys Fhe Thr Val Gly Thr Ala 20 25 30
Ser lie Leu He Gly Ser Leu Met Tyr Leu Gly Thr Gin Gin Glu Ala 35 40 45
Glu Ala Ala Glu Asn Asn lie Glu Asn Pro Thr Thr Leu Lys Asp Asn 50 55 60
Val Gin Ser Lys Glu Val Lys lie Glu Glu Val Thr Asn Lys Asp Thr 65 70 75 80
Ala Pro Gin Gly Val Glu Ala Lys Ser Glu Val Thr Ser Asn Lys Asp 85 90 95
Thr lie Glu His Glu Ala Ser Val Lys Ala Glu Asp He Ser Lys Lys 100 105 110
Glu Asp Thr Pro Lys Glu Val Ala Asn Val Ala Glu Val Gin Pro Lys 115 120 125
Ser Ser Val Thr His Asn Ala Glu Ala Pro Lys Val Arg Lys Ala Arg 130 135 140
Ser Val Asp Glu Gly Ser Phe Asp lie Thr Arg Asp Ser Lys Asn Val 145 150 155 160
Val Glu Ser Thr Pro He Thr He Gin Gly Lys Glu His Phe Glu Gly 165 170 175
Tyr Gly Ser Val Asp lie Gin Lys Asn Pro Thr Asp Leu Gly Val Ser 180 185 190
Glu Val Thr Arg Phe Asn Val Gly Asn Glu Ser Asn Gly Leu lie Gly 195 200 205
Ala Leu Gin Leu Lys Asn Lys lie Asp Phe Ser Lys Asp Phe Asn Phe 210 215 220
Lys Val Arg Val Ala Asn Asn His Gin Ser Asn Thr Thr Gly Ala Asp 225 230 235 240
Gly Trp Gly Phe Leu Phe Ser Lys Gly Asn Ala Glu Glu Tyr Leu Thr 245 250 255
Asn Gly Gly He Leu Gly Asp Lys Gly Leu Val Asn Ser Gly Gly Phe 260 265 270
Lys He Asp Thr Gly Tyr lie Tyr Thr Ser Ser Met Asp Lys Thr Glu 275 280 285
Lys Gin Ala Gly Gin Gly Tyr Arg Gly Tyr Gly Ala Phe Val Lys Asn 290 295 300
Asp Ser Ser Gly Asn Ser Gin Met Val Gly Glu Asn lie Asp Lys Ser 305 310 315 320
Lys Thr Asn Phe Leu Asn Tyr Ala Asp Asn Ser Thr Asn Thr Ser Asp 325 330 335
Gly Lys Phe His Gly Gin Arg Leu Asn Asp Val lie Leu Thr Tyr Val 340 345 350
Ala Ser Thr Gly Lys Met Arg Ala Glu Tyr Ala Gly Lys Thr Trp Glu 355 360 365
Thr Ser lie Thr Asp Leu Gly Leu Ser Lys Asn Gin Ala Tyr Asn Phe 370 375 380
Leu lie Thr Ser Ser Gin Arg Trp Gly Leu Asn Gin Gly lie Asn Ala 385 390 395 400
Asn Gly Trp Met Arg Thr Asp Leu Lys Gly Ser Glu Phe Thr Phe Thr 405 410 415
Pro Glu Ala Pro Lys Thr lie Thr Glu Leu Glu Lys Lys Val Glu Glu 420 425 430 lie Pro Phe Lys Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 44- 119629-序列表.doc 200815028 435 440 445
Thr Glu Lys Val Thr Arg Glu Gly Gin Lys Gly Glu Lys Thr lie Thr 450 455 460
Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu lie lie Ser Lys Gly 465 470 475 480
Glu Ser Lys Glu Glu lie Thr Lys Asp Pro lie Asn Glu Leu Thr Glu 485 490 495
Tyr Gly Pro Glu Thr lie Ala Pro Gly His Arg Asp Glu Phe Asp Pro 500 505 510
Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly lie 515 520 525
Lys Asn Pro Glu Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 530 535 540
Thr Lys Tyr Gly Pro Val Lys Gly Asp Ser lie Val Glu Lys Glu Glu 545 550 555 560 lie Pro Phe Glu lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 565 570 575
Thr Glu Lys Val Thr Arg Glu Gly Gin Lys Gly Glu Lys Thr lie Thr 580 585 590
Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu lie lie Ser Lys Gly 595 600 605
Glu Ser Lys Glu Glu lie Thr Lys Asp Pro He Asn Glu Leu Thr Glu 610 615 620
Tyr Gly Pro Glu Thr lie Ala Fro Gly His Arg Asp Glu Phe Asp Pro 625 630 635 640
Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly lie 645 650 655
Lys Asn Pro Glu Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 660 665 670
Thr Lys Tyr Gly Pro Val Lys Gly Asp Ser lie Val Glu Lys Glu Glu 675 680 685 lie Pro Phe Lys Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 690 695 700
Thr Glu Lys Val Thr Arg Glu Gly Gin Lys Gly Glu Lys Thr He Thr 705 710 715 720
Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu lie He Ser Lys Gly 725 730 735
Glu Ser Lys Glu Glu He Thr Lys Asp Pro lie Asn Glu Leu Thr Glu 740 745 750
Tyr Gly Pro Glu Thr lie Thr Fro Gly His Arg Asp Glu Phe Asp Pro 755 760 765
Lys Leu Pro Thr Gly Glu Lys Glu Glu Val Pro Gly Lys Pro Gly lie 770 775 780
Lys Asn Pro Glu Thr Gly Asp Val Val Arg Pro Pro Val Asp Ser Val 785 790 795 800
Thr Lys Tyr Gly Pro Val Lys Gly Asp Ser lie Val Glu Lys Glu Glu 805 810 815 lie Pro Phe Glu Lys Glu Arg Lys Phe Asn Pro Asp Leu Ala Pro Gly 820 825 830
Thr Glu Lys Val Thr Arg Glu Gly Gin Lys Gly Glu Lys Thr lie Thr 835 840 845
Thr Pro Thr Leu Lys Asn Pro Leu Thr Gly Glu lie lie Ser Lys Gly 850 855 860
Glu Ser Lys Glu Glu lie Thr Lys Asp Pro Val Asn Glu Leu Thr Glu 865 870 875 880
Phe Gly Gly Glu Lys lie Pro Gin Gly His Lys Asp lie Phe Asp Pro 885 890 895
Asn Leu Pro Thr Asp Gin Thr Glu Lys Val Pro Gly Lys Pro Gly He 900 905 910
Lys Asn Pro Asp Thr Gly Lys Val He Glu Glu Pro Val Asp Asp Val 915 920 925 lie Lys His Gly Pro Lys Thr Gly Thr Pro Glu Thr Lys Thr Val Glu 930 935 940 lie Pro Phe Glu Thr Lys Arg Glu Phe Asn Pro Lys Leu Gin Pro Gly 945 950 955 960
Glu Glu Arg Val Lys Gin Glu Gly Gin Fro Gly Ser Lys Thr lie Thr 965 970 975
Thr Pro lie Thr Val Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly 980 985 990
Gin Pro Thr Glu Glu lie Thr Lys Gin Pro Val Asp Lys lie Val Glu 995 1000 1005
Phe Gly Gly Glu Lys Pro Lys Asp Pro Lys Gly Fro Glu Asn Pro Glu 1010 1015 1020
Lys Pro Ser Arg Pro Thr His Pro Ser Gly Pro Val Asn Pro Asn Asn 1025 1030 1035 1040 45 119629-序列表.doe 200815028
Pro Gly Leu Ser Lys Asp Arg Ala Lys Pro Asn Gly Pro Val His Ser 1045 1050 1055
Met Asp Lys Asn Asp Lys Val Lys Lys Ser Lys lie Ala Lys Glu Ser 1060 1065 1070
Val Ala Asn Gin Glu Lys Lys Arg Ala Glu Leu Pro Lys Thr Gly Leu 1075 1080 1085
Glu Ser Thr Gin Lys Gly Leo lie Phe Ser Ser lie lie Gly lie Ala 1090 1095 1100
Gly Leu Met Leu Leu Ala Arg Arg Arg Lys Asn 1105 1110 1115 <210> 17 <211〉 1469 <212> PRT <213〉葡萄球菌 <400> 17
Met Gly Lys Arg Arg Gin Gly Fro He Asn Lys Lys Val Asp Phe Leu I 5 10 15
Pro Asn Lys Leu Asn lys Tyr Ser He Arg Lys Phe Thr Val Gly Thr 20 25 30
Ala Ser lie Leu Leu Gly Ser Thr Leu He Phe Gly Ser Ser Ser His 35 40 45
Glu Ala Lys Ala Ala Glu Glu Lys Gin Val Asp Pro lie Thr Gin Ala 50 55 60
Asn Gin Asn Asp Ser Ser Glu Arg Ser Leu Glu Asn Thr Asn Gin Pro
65 70 75 80
Thr Val Asn Asn Glu Ala Pro Gin Met Ser Ser Thr Leu Gin Ala Glu 85 90 95
Glu Gly Ser Asn Ala Glu Ala Pro Asn Val Pro Thr lie Lys Ala Asn 100 105 110
Ser Asp Asn Asp Thr Gin Thr Gin Phe Ser Glu Ala Fro Thr Arg Asn 115 120 125
Asp Leu Ala Arg Lys Glu Asp lie Pro Ala Val Ser Lys Asn Glu Glu 130 135 140
Leu Gin Ser Ser Gin Pro Asn Thr Asp Ser Lys lie Glu Pro Thr Thr 145 150 155 160
Ser Glu Pro Val Asn Leu Asn Tyr Ser Ser Pro Phe Met Ser Leu Leu 165 170 175
Ser Met Pro Ala Asp Ser Ser Ser Asn Asn Thr Lys Asn Thr lie Asp 180 185 190 lie Pro Pro Thr Thr Val Lys Gly Arg Asp Asn Tyr Asp Phe Tyr Gly 195 200 205
Arg Val Asp lie Gin Ser Asn Pro Thr Asp Leu Asn Ala Thr Asn Leu 210 215 220
Thr Arg Tyr Asn Tyr Gly Gin Pro Pro Gly Thr Thr Thr Ala Gly Ala 225 230 235 240
Val Gin Phe Lys Asn Gin Val Ser Phe Asp Lys Asp Phe Asp Phe Asn 245 250 255 lie Arg Val Ala Asn Asn Arg Gin Ser Asn Thr Thr Gly Ala Asp Gly 260 265 270
Trp Gly Phe Met Phe Ser Lys Lys Asp Gly Asp Asp Phe Leu Lys Asn 275 280 285
Gly Gly lie Leu Arg Glu Lys Gly Thr Pro Ser Ala Ala Gly Phe Arg 290 295 300
He Asp Thr Gly Tyr Tyr Asn Asn Asp Pro Leu Asp Lys He Gin Lys 305 310 315 320
Gin Ala Gly Gin Gly Tyr Arg Gly Tyr Gly Thr Phe Val Lys Asn Asp 325 330 335
Ser Gin Gly Asn Thr Ser Lys Val Gly Ser Gly Thr Pro Ser Thr Asp 340 345 350
Phe Leu Asn Tyr Ala Asp Asn Thr Thr Asn Asp Leu Asp Gly Lys Phe 355 360 365
His Gly Gin Lys Leu Asn Asn Val Asn Leu Lys Tyr Asn Ala Ser Asn 370 375 380
Gin Thr Phe Thr Ala Thr Tyr Ala Gly Lys Thr Trp Thr Ala Thr Leu 385 390 395 400
Ser Glu Leu Gly Leu Ser Pro Thr Asp Ser Tyr Asn Phe Leu Val Thr 405 410 415
Ser Ser Gin Tyr Gly Asn Gly Asn Ser Gly Thr Tyr Ala Asp Gly Val 420 425 430
Met Arg Ala Asp Leu Asp Gly Ala Thr Leu Thr Tyr Thr Pro Lys Ala 435 440 445
Val Asp Gly Asp Pro lie Thr Ser Thr Lys Glu lie Pro Phe Asn Lys 46· 119629-序列表.doc 200815028 450 455 460
Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 465 470 475 480
Gin Lys Gly Glu Pro Gly lie Glu Thr Thr Thr Thr Pro Thr Tyr Val 485 490 495
Asn Pro Asn Thr Gly Glu Lys Val Gly Glu Gly Thr Pro Thr Thr Lys 500 505 510 lie Thr Lys Gin Pro Val Asp Glu lie Val His Tyr Gly Gly Glu Glu 515 520 525 lie Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 530 535 540
Ser Gin Thr Thr Gin Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 545 550 555 560
Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 565 570 575
Val Asp Gly Asp Pro lie Thr Ser Thr Glu Glu lie Pro Phe Asp Lys 580 585 590
Lys Arg Glu Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val Lys 595 600 605
Gin Lys Gly Glu Pro Gly Thr Lys Thr lie Thr Thr Pro Thr Thr Lys 610 615 620
Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 625 630 635 640
He Thr Lys Gin Pro Val Asp Glu lie Thr Glu Tyr Gly Gly Glu Glu 645 650 655 lie Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 660 665 670
Ser Gin Glu Asp Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 675 680 685
Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 690 695 700
Val Asp Gly Asp Pro lie Thr Ser Thr Glu Glu lie Pro Phe Asp Lys 705 710 715 720
Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val ~ 725 730 735
Gin Lys Gly Glu Pro Gly Thr Lys Thr lie Thr Thr Pro Thr Thr Lys 740 745 750
Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 755 760 765 lie Thr Lys Gin Pro Val Asp Glu lie Val His Tyr Gly Gly Glu Glu 770 775 780 lie Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 785 790 795 800
Ser Gin Glu Asp Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 805 810 815
Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 820 825 830
Val Asp Gly Asp Pro lie Thr Ser Thr Glu Glu lie Pro Phe Asp Lys 835 840 845
Lys Arg Glu Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val Lys 850 855 860
Gin Lys Gly Glu Pro Gly Thr Lys Thr lie Thr Thr Pro Thr Thr Lys 865 870 875 880
Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 885 890 895
Val Thr Lys Gin Pro Val Asp Glu lie Val His Tyr Gly Gly Glu Glu 900 905 910 lie Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 915 920 925
Ser Gin Glu Asp Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 930 935 940
Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 945 950 955 960
Vai Asp Gly Asp Pro He Thr Ser Thr Glu Glu lie Pro Phe Asp Lys 965 970 975
Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 980 985 990
Gin Lys Gly Glu Pro Gly Thr Lys Thr lie Thr Thr Pro Thr Thr Lys 995 1000 1005
Asn Pro Leu Thr Gly Glu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 1010 1015 1020 lie Thr Lys Gin Pro Val Asp Glu He Val His Tyr Gly Gly Glu Glu 1025 . 1030 1035 1040
He Lys Pro Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Lys Gly 1045 1050 1055 -47- 119629-序列表.doc 200815028
Ser Gin Thr Thr Gin Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 1060 1065 1070
Gly Glu Vai Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Fro 1075 1080 1085
Val Asp Gly Asp Pro lie Thr Ser Thr Glu Glu lie Pro Phe Asp Lys 1090 1095 1100
Lys Arg Glu Phe Asp Pro Asn Leu Ala Pro Gly Thr Glu Lys Val Val 1105 1110 1115 1120
Gin Lys Gly Glu Pro Gly Thr Lys Thr lie Thr Thr Pro Thr Thr Lys 1125 1130 1135
Asn Pro Leu Thr Gly Giu Lys Val Gly Glu Gly Glu Pro Thr Glu Lys 1140 1145 1150 lie Thr Lys Gin Pro Val Asp Glu lie Val His Tyr Gly Gly Glu Gin 1155 1160 1165
He Pro Gin Gly His Lys Asp Glu Phe Asp Pro Asn Ala Pro Val Asp 1170 1175 1180
Ser Lys Thr Glu Val Pro Gly Lys Pro Gly Val Lys Asn Pro Asp Thr 1185 1190 1195 1200
Gly Glu Val Val Thr Pro Pro Val Asp Asp Val Thr Lys Tyr Gly Pro 1205 1210 1215
Lys Val Gly Asn Pro lie Thr Ser Thr Glu Glu lie Pro Phe Asp Lys 1220 1225 1230
Lys Arg Val Phe Asn Pro Asp Leu Lys Pro Gly Glu Glu Arg Val Lys 1235 1240 1245
Gin Lys Gly Glu Pro Gly Thr Lys Thr lie Thr Thr Pro He Leu Val 1250 1255 1260
Asn Pro He Thr Gly Glu Lys Val Gly Glu Gly Lys Ser Thr Glu Lys 1265 1270 1275 1280
Val Thr Lys Gin Pro Val Asp Glu He Val Glu Tyr Gly Pro Thr Lys 1285 1290 1295
Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly 1300 1305 1310
Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Thr Pro Ala Glu 1315 1320 1325
Pro Gly Lys Fro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro 1330 1335 1340
Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly 1345 1350 1355 1360
Thr Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly Lys Fro Ala Glu 1365 1370 1375
Pro Gly Lys Pro Ala Glu Pro Gly Thr Pro Ala Glu Pro Gly Lys Pro 1380 1385 1390
Ala Glu Pro Gly Thr Pro Ala Glu Pro Gly Lys Pro Ala Glu Pro Gly 1395 1400 1405
Thr Pro Thr Gin Ser Gly Ala Pro Glu Gin Pro Asn Arg Ser Met His 1410 1415 1420
Ser Thr Asp Asn Lys Asn Gin Leu Pro Asp Thr Gly Glu Asn Arg Gin 1425 1430 1435 1440
Ala Asn Glu Gly Thr Leu Val Gly Ser Leu Leu Ala lie Val Gly Ser 1445 1450 1455
Leu Phe lie Phe Gly Arg Arg Lys Lys Gly Asn Glu Lys 1460 1465 <210> 18 <211〉 167 <212> PRT <213〉葡萄球菌 <400> 18
Met Lys Lys Leu Tyr Thr Ser Tyr Gly Thr Tyr Gly Phe Leu His Gin 15 10 15
He Lys lie Asn Asn Pro Thr His Gin Leu Phe Gin Phe Ser Ala Ser 20 25 30
Asp Tbr Ser Val lie Phe Glu Glu Thr Asp Gly Glu Thr Val Leu Lys 35 40 45
Ser Pro Ser lie Tyr Glu Val lie Lys Glu He Gly Glu Phe Ser Glu 50 55 60
His His Phe Tyr Cys Ala lie Phe lie Pro Ser Thr Glu Asp His Ala 65 70 75 80
Tyr Gin Leu Glu Lys Lys Leu He Ser Val Asp Asp Asn Phe Arg Asn 85 90 95
Phe Gly Gly Phe Lys Ser Tyr Arg Leu Leu Arg Pro Ala Lys Gly Thr 100 105 110
Thr Tyr Lys lie Tyr Phe Gly Phe Ala Asp Arg His Ala Tyr Glu Asp 48- 119629·序列表.doc 200815028 115 120 125
Phe Lys Gin Ser Asp Ala Phe Asn Asp His Phe Ser Lys Asp Ala Leu 130 135 140
Ser His Tyr Phe Gly Ser Ser Gly Gin His Ser Ser Tyr Phe Glu Arg 145 150 155 160
Tyr Leu Tyr Fro lie Lys Glu 165 <2I0> 19
<211〉 167 <212> PRT 〈213>葡萄球菌 <400> 19
Met Tyr Leu Tyr 丁hr Ser Tyr Gly Thr Tyr Gin Phe Leu Asn Gin lie 1 5 10 15
Lys Leu Asn His Gin Glu Arg Ser Leu Phe Gin Phe Ser Thr Asn Asp 20 25 30
Ser Ser lie lie Leu Glu Glu Ser Glu Gly Lys Ser lie Leu Lys His 35 40 45
Pro Ser Ala Tyr Gin Val He Asp Ser Thr Gly Glu Phe Asn Glu His 50 55 60
His Phe Tyr Ser Ala lie Phe Val Pro Thr Ser Glu Asp His Arg Gin 65 70 75 80
Gin Leu Glu Lys Lys Leu Leu Leu Val Asp Val Pro Leu Arg Asn Phe 85 90 95
Gly Gly Phe Lys Ser Tyr Arg Leu Leu Lys Pro Thr Glu Gly Ser Thr 100 105 110
Tyr Lys lie Tyr Phe Gly Phe Ala Asn Arg Thr Ala Tyr Gly Asp Phe 115 120 125
Lys Ala Ser Asp He Phe Asn Glu Asn Phe Ser Lys Asp Ala Leu Ser 130 135 140
Gin Tyr Phe Gly Ala Ser Gly Gin His Ser Ser Tyr Phe Glu Arg Tyr 145 150 155 160
Leu Tyr Pro lie Glu Asp His 165 <210> 20 <211〉 1141 <212> PRT <213〉葡萄球菌 <400〉 20
Met lie Asn Arg Asp Asn Lys Lys Ala lie Thr Lys Lys Gly Met lie 15 10 15
Ser Asn Arg Leu Asn Lys Phe Ser lie Arg Lys Tyr Thr Val Gly Thr 20 25 30
Ala Ser lie Leu Val Gly Thr Thr Leu lie Phe Gly Leu Gly Asn Gin 35 40 45
Glu Ala Lys Ala Ala Glu Asn Thr Ser Thr Glu Asn Ala Lys Gin Asp 50 55 60
Asp Ala Thr Thr Ser Asp Asn Lys Glu Val Val Ser Glu Thr Glu Asn 65 70 75 80
Asn Ser Thr Thr Glu Asn Asp Ser Thr Asn Pro lie Lys Lys Glu Thr 85 90 95
Asn Thr Asp Ser Gin Pro Glu Ala Lys Glu Glu Ser Thr Thr Ser Ser 100 105 110
Thr Gin Gin Gin Gin Asn Asn Val Thr Ala Thr Thr Glu Thr Lys Pro 115 120 125
Gin Asn lie Glu Lys Glu Asn Val Lys Pro Ser Thr Asp Lys Thr Ala 130 135 140
Thr Glu Asp Thr Ser Val lie Leu Glu Glu Lys Lys Ala Pro Asn Tyr 145 150 155 160
Thr Asn Asn Asp Val Thr Thr Lys Pro Ser Thr Ser Glu lie Gin Thr 165 170 175
Lys Pro Thr Thr Pro Gin Glu Ser Thr Asn lie Glu Asn Ser Gin Pro 180 185 190
Gin Pro Thr Pro Ser Lys Val Asp Asn Gin Val Thr Asp Ala Thr Asn 195 200 205
Pro Lys Glu Pro Val Asn Val Ser Lys Glu Glu Leu Lys Asn Asn Pro 210 215 220
Glu Lys Leu Lys Glu Leu Val Arg Asn Asp Asn Asn Thr Asp Arg Ser 49· 119629-序列表.doc 200815028 225 230 235 240
Thr Lys Pro Val Ala Thr Ala Pro Thr Ser Val Ala Pro Lys Arg Leu 245 250 255
Asn Ala Lys Met Arg Phe Ala Val Ala Gin Pro Ala Ala Val Ala Ser 260 265 270
Asn Asn Val Asn Asp Leu lie Thr Val Thr Lys Gin Thr He Lys Val 275 280 285
Gly Asp Gly Lys Asp Asn Val Ala Ala Ala His Asp Gly Lys Asp lie 290 295 300
Glu Tyr Asp Thr Glu Phe Thr lie Asp Asn Lys Val Lys Lys Gly Asp 305 310 315 320
Thr Met Thr lie Asn Tyr Asp Lys Asn Val He Pro Ser Asp Leu Thr 325 330 335
Asp Lys Asn Asp Pro lie Asp lie Thr Asp Pro Ser Gly Glu Val lie 340 345 350
Ala Lys Gly Thr Phe Asp Lys Ala Thr Lys Gin lie Thr Tyr Thr Phe 355 360 365
Thr Asp Tyr Val Asp Lys Tyr Glu Asp lie Lys Ala Arg Leu Thr Leu 370 375 380
Tyr Ser Tyr lie Asp Lys Gin Ala Val Pro Asn Glu Thr Ser Leu Asn 385 390 395 400
Leu Thr Phe Ala Thr Ala Gly Lys Glu Thr Ser Gin Asn Val Ser Val 405 410 415
Asp Tyr Gin Asp Pro Met Val His Gly Asp Ser Asn lie Gin Ser lie 420 425 430
Phe Thr Lys Leu Asp Glu Asn Lys Gin Thr lie Glu Gin Gin lie Tyr 435 440 445
Val Asn Pro Leu Lys Lys Thr Ala Thr Asn Thr Lys Val Asp lie Ala 450 455 460
Gly Ser Gin Val Asp Asp Tyr Gly Asn lie Lys Leu Gly Asn Gly Ser 465 470 475 480
Thr lie He Asp Gin Asn Thr Glu lie Lys Val Tyr Lys Val Asn Fro 485 490 495
Asn Gin Gin Leu Pro Gin Ser Asn Arg He Tyr Asp Phe Ser Gin Tyr 500 505 510
Glu Asp Val Thr Ser Gin Phe Asp Asn Lys Lys Ser Phe Ser Asn Asn 515 520 525
Val Ala Thr Leu Asp Phe Gly Asp He Asn Ser Ala Tyr lie He Lys 530 535 540
Val Val Ser Lys Tyr Thr Pro Thr Ser Asp Gly Glu Leu Asp lie Ala 545 550 555 560
Gin Gly Thr Ser Met Arg Thr Thr Asp Lys Tyr Gly Tyr Tyr Asn Tyr 565 570 575
Ala Gly Tyr Ser Asn Phe lie Val Thr Ser Asn Asp Thr Gly Gly Gly 580 585 590
Asp Gly Thr Val Lys Pro Glu Glu Lys Leu Tyr Lys lie Gly Asp Tyr 595 600 605
Val Trp Glu Asp Val Asp Lys Asp Gly Val Gin Gly Thr Asp Ser Lys 610 615 620
Glu Lys Pro Met Ala Asn Val Leu Val Thr Leu Thr Tyr Pro Asp Gly 625 630 635 640
Thr Thr Lys Ser Val Arg Thr Asp Ala Asn Gly His Tyr Glu Phe Gly 645 650 655
Gly Leu Lys Asp Gly Glu Thr Tyr Thr Val Lys Phe Glu Thr Pro Ala 660 665 670
Gly Tyr Leu Pro Thr Lys Val Asn Gly Thr Thr Asp Gly Glu Lys Asp 675 680 685
Ser Asn Gly Ser Ser lie Thr Val Lys lie Asn Gly Lys Asp Asp Met 690 695 700
Ser Leu Asp Thr Gly Phe Tyr Lys Glu Pro Lys Tyr Asn Leu Gly Asp 705 710 715 720
Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly lie Gin Asp Ala Asn Glu 725 730 735
Pro Gly lie Lys Asp Val Lys Val Thr Leu Lys Asp Ser Thr Gly Lys 740 745 750
Val lie Gly Thr Thr Thr Thr Asp Ala Ser Gly Lys Tyr Lys Phe Thr 755 760 765
Asp Leu Asp Asn Gly Asn Tyr Thr Val Glu Phe Glu Thr Fro Ala Gly 770 775 780
Tyr Thr Pro Thr Val Lys Asn Thr Thr Ala Glu Asp Lys Asp Ser Asn 785 790 795 800
Gly Leu Thr Thr Thr Gly Val He Lys Asp Ala Asp Asn Met Thr Leu 805 810 815
Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr Ser Leu Gly Asp Tyr Val 820 825 830 -50- 119629·序列表.doc 200815028
Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gin Asp Ser Thr Glu Lys Gly 835 840 845 lie Lys Asp Val Lys Val Thr Leu Leu Asn Glu Lys Gly Glu Val lie 850 855 860
Gly Thr Thr Lys Thr Asp Glu Asn Gly Lys Tyr Arg Phe Asp Asn Leu 865 870 875 880
Asp Ser Gly Lys Tyr Lys Val He Phe Glu Lys Pro Ala Gly Leu Thr 885 890 895
Gin Thr Val Thr Asn Thr Thr Glu Asp Asp Lys Asp Ala Asp Gly Gly 900 905 910
Glu Val Asp Val Thr lie Thr Asp His Asp Asp Phe He Leu Asp Asn 915 920 925
Gly Tyr Phe Glu Glu Asp Thr Ser Asp Ser Asp Ser Asp Ser Asp Ser 930 935 940
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 945 950 955 960
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 965 970 975
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 980 985 990
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 995 1000 1005
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1010 1015 1020
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1025 1030 1035 1040
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1045 1050 1055
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 1060 1065 1070
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys His Thr Pro Val 1075 1080 1085
Lys Pro Met Ser Thr Thr Lys Asp His His Asn Lys Ala Lys Ala Leu 1090 1095 1100
Pro Glu Thr Gly Ser Glu Asn Asn Gly Ser Asn Asn Ala Thr Leu Phe 1105 1110 1115 1120
Gly Gly Leu Phe Ala Ala Leu Gly Ser Leu Leu Leu Phe Gly Arg Arg 1125 1130 1135
Lys Lys Gin Asn Lys 1140 <210> 21 <211> 1056 <212> PRT <213〉葡萄球菌 <400〉 21
Met lie Asn Lys Lys Asn Asn Leu Leu Thr Lys Lys Lys Pro lie Ala 1 5 10 15
Asn Lys Ser Asn Lys Tyr Ala lie Arg Lys Phe Thr Val Gly Thr Ala 20 25 30
Ser lie Val lie Gly Ala Thr Leu Leu Phe Gly Leu Gly His Asn Glu 35 40 45
Ala Lys Ala Glu Glu Asn Ser Val Gin Asp Val Lys Asp Ser Asn Thr 50 55 60
Asp Asp Glu Leu Ser Asp Ser Asn Asp Gin Ser Ser Asp Glu Glu Lys 65 70 75 80
Asn Asp Val He Asn Asn Asn Gin Ser lie Asn Thr Asp Asp Asn Asn 85 90 95
Gin lie lie Lys Lys Glu Glu Thr Asn Asn Tyr Asp Gly lie Glu Lys 100 105 110
Arg Ser Glu Asp Arg Thr Glu Ser Thr Thr Asn Val Asp Glu Asn Glu 115 120 125
Ala Thr Phe Leu Gin Lys Thr Pro Gin Asp Asn Thr His Leu Thr Glu 130 135 140
Glu Glu Val Lys Glu Ser Ser Ser Val Glu Ser Ser Asn Ser Ser He 145 150 155 160
Asp Thr Ala Gin Gin Pro Ser His Thr Thr lie Asn Arg Glu Glu Ser 165 170 175
Val Gin Thr Ser Asp Asn Val Glu Asp Ser His Val Ser Asp Phe Ala 180 185 190
Asn Ser Lys lie Lys Glu Ser Asn Thr Glu Ser Gly Lys Glu Glu Asn 195 200 205
Thr lie Glu Gin Pro Asn Lys Val Lys Glu Asp Ser Thr Thr Ser Gin 51- 119629-序列表.doc 200815028 210 215 220
Pro Ser Gly Tyr Thr Asn lie Asp Glu Lys He Ser Asn Gin Asp GIu 225 230 235 240
Leu Leu Asn Leu Pro lie Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu 245 250 255
Ser Thr Thr Ser Ala Gin Pro Ser lie Lys Arg Val Thr Val Asn Gin 260 265 270
Leu Ala Ala Glu Gin Gly Ser Asn Val Asn His Leu lie Lys Val Thr 275 280 285
Asp Gin Ser He Thr Glu Gly Tyr Asp Asp Ser Glu Gly Val lie Lys 290 295 300
Ala His Asp Ala Glu Asn Leu He Tyr Asp Val Thr Phe Glu Val Asp 305 310 315 320
Asp Lys Val Lys Ser Gly Asp Thr Met Thr Val Asp lie Asp Lys Asn 325 330 335
Thr Val Pro Ser Asp Leu Thr Asp Ser Phe Thr lie Pro Lys lie Lys 340 345 350
Asp Asn Ser Gly Glu lie lie Ala Thr Gly Thr Tyr Asp Asn Lys Asn 355 360 365
Lys Gin lie Thr Tyr Thr Phe Thr Asp Tyr Val Asp Lys Tyr Glu Asn 370 375 380 lie Lys Ala His Leu Lys Leu Thr Ser Tyr lie Asp Lys Ser Lys Val 385 390 395 400
Pro Asn Asn Asn Thr Lys Leu Asp Val Glu Tyr Lys Thr Ala Leu Ser 405 410 415
Ser Val Asn Lys Thr lie Thr Val Glu Tyr Gin Arg Pro Asn Glu Asn 420 425 430
Arg Thr Ala Asn Leu Gin Ser Met Phe Thr Asn lie Asp Thr Lys Asn 435 440 445
His Thr Val Glu Gin Thr lie Tyr lie Asn Pro Leu Arg Tyr Ser Ala 450 455 460
Lys Glu Thr Asn Val Asn lie Ser Gly Asn Gly Asp Glu Gly Ser Thr 465 470 475 480 lie lie Asp Asp Ser Thr lie lie Lys Val Tyr Lys Val Gly Asp Asn 485 490 495
Gin Asn Leu Pro Asp Ser Asn Arg lie Tyr Asp Tyr Ser Glu Tyr Glu 500 505 510
Asp Val Thr Asn Asp Asp Tyr Ala Gin Leu Gly Asn Asn Asn Asp Val 515 520 525
Asn lie Asn Phe Gly Asn lie Asp Ser Pro Tyr lie lie Lys Val He 530 535 540
Ser Lys Tyr Asp Pro Asn Lys Asp Asp Tyr Thr Thr lie Gin Gin Thr 545 550 555 560
Val Thr Met Gin Thr Thr lie Asn Glu Tyr Thr Gly Glu Phe Arg Thr 565 570 575
Ala Ser Tyr Asp Asn Thr lie Ala Phe Ser Thr Ser Ser Gly Gin Gly 580 585 590
Gin Gly Asp Leu Pro Pro Glu Lys Thr Tyr Lys lie Gly Asp Tyr Val 595 600 605
Trp Glu Asp Val Asp Lys Asp Gly lie Gin Asn Thr Asn Asp Asn Glu 610 615 620
Lys Pro Leu Ser Asn Val Leu Val Thr Leu Thr Tyr Pro Asp Gly Thr 625 630 635 640
Ser Lys Ser Val Arg Thr Asp Glu Asp Gly Lys Tyr Gin Phe Asp Gly 645 650 655
Leu Lys Asn Gly Leu Thr Tyr Lys lie Thr Phe Glu Thr Pro Glu Gly 660 665 670
Tyr Thr Pro Thr Leu Lys His Ser Gly Thr Asn Pro Ala Leu Asp Ser 675 680 685
Glu Gly Asn Ser Val Trp Val Thr lie Asn Gly Gin Asp Asp Met Thr 690 695 700 lie Asp Ser Gly Phe Tyr Gin Thr Pro Lys Tyr Ser Leu Gly Asn Tyr 705 710 715 720
Val Trp Tyr Asp Thr Asn Lys Asp Gly He Gin Gly Asp Asp Glu Lys 725 730 735
Gly lie Ser Gly Val Lys Val Thr Leu Lys Asp Glu Asn Gly Asn He 740 745 750 lie Ser Thr Thr Thr Thr Asp Glu Asn Gly Lys Tyr Gin Phe Asp Asn 755 760 765
Leu Asn Ser Gly Asn Tyr lie Val His Phe Asp Lys Pro Ser Gly Met 770 775 780
Thr Gin Thr Thr Thr Asp Ser Gly Asp Asp Asp Glu Gin Asp Ala Asp 785 790 795 800
Gly Glu Glu Val His Val Thr lie Thr Asp His Asp Asp Phe Ser lie 805 810 815 -52 - 119629-序列表.doc 200815028
Asp Asn Gly Tyr Tyr Asp Asp Glu Ser Asp Ser Asp Ser Asp Ser Asp 820 825 830
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 835 840 845
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 850 855 860
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 865 870 875 880
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 885 890 895
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 900 905 910
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 915 920 925
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 930 935 940
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 945 950 955 960
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 965 970 975
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 980 985 990
Ser Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Leu Gly Asn Ser 995 1000 1005
Ser Asp Lys Ser Thr Lys Asp Lys Leu Pro Asp Thr Gly Ala Asn Glu 1010 1015 1020
Asp Tyr Gly Ser Lys Gly Thr Leu Leu Gly Thr Leu Phe Ala Gly Leu
1025 1030 1035 1040
Gly Ala Leu Leu Leu Gly Lys Arg Arg Lys Asn Arg Lys Asn Lys Asn 1045 1050 1055
<210> 22 <211〉 486 <212〉 PRT <213>葡萄球菌 <400〉 22
Met Ser Asn Asn Phe Lys Asp Asp Fhe Glu Lys Asn Arg Gin Ser lie 15 10 15
Asp Thr Asn Ser His Gin Asp His Thr Glu Asp Val Glu Lys Asp Gin 20 25 30
Ser Glu Leu Glu His Gin Asp Thr lie Glu Asn Thr Glu Gin Gin Phe 35 40 45
Pro Pro Arg Asn Ala Gin Arg Arg Lys Arg Arg Arg Asp Leu Ala Thr 50 55 60
Asn His Asn Lys Gin Val His Asn Glu Ser Gin Thr Ser Glu Asp Asn 65 70 75 80
Val Gin Asn Glu Ala Gly Thr lie Asp Asp Arg Gin Val Glu Ser Ser 85 90 95
His Ser Thr Glu Ser Gin Glu Pro Ser His Gin Asp Ser Thr Pro Gin 100 105 110
His Glu Glu Glu Tyr Tyr Asn Lys Asn Ala Phe Ala Met Asp Lys Ser 115 120 125
His Pro Glu Pro He Glu Asp Asn Asp Lys His Glu Thr He Lys Asp 130 135 140
Ala Glu Asn Asn Thr Glu His Ser Thr Val Ser Asp Lys Ser lie Ala 145 150 155 160
Glu Gin Ser Gin Gin Pro Lys Pro Tyr Phe Ala Thr Gly Ala Asn Gin 165 170 175
Ala Asn Thr Ser Lys Asp Lys His Asp Asp Val Thr Val Lys Gin Asp 180 185 190
Lys Asp Glu Ser Lys Asp His His Ser Gly Lys Lys Gly Ala Ala He 195 200 205
Gly Ala Gly Thr Ala Gly Val Ala Gly Ala Ala Gly Ala Met Gly Val 210 215 220
Ser Lys Ala Lys Lys His Ser Asn Asp Ala Gin Asn Lys Ser Asn Ser 225 230 235 240
Asp Lys Ser Asn Asn Ser Thr Glu Asp Lys Ala Ser Gin Asp Lys Ser 245 250 255
Lys Asp His His Asn Gly Lys Lys Gly Ala Ala He Gly Ala Gly Thr 260 265 270
Ala Gly Leu Ala Gly Gly Ala Ala Ser Lys Ser Ala Ser Ala Ala Ser 275 280 285
Lys Pro His Ala Ser Asn Asn Ala Ser Gin Asn His Asp Glu His Asp 53- 119629·序列表.doc 200815028 290 295 300
Asn His Asp Arg Asp Lys Glu Arg Lys Lys Gly Gly Met Ala Lys Val 305 310 315 320
Leu Leu Pro Leu lie Ala Ala Val Leu lie He Gly Ala Leu Ala lie 325 330 335
Phe Gly Gly Met Ala Leu Asn Asn His Asn Asn Gly Thr Lys Glu Asn 340 345 350
Lys lie Ala Asn Thr Asn Lys Asn Asn Ala Asp Glu Ser Lys Asp Lys 355 360 365
Asp 丁hr Ser Lys Asp Ala Ser Lys Asp Lys Ser Lys Ser Thr Asp Ser 370 375 380
Asp Lys Ser Lys Glu Asp Gin Asp Lys Ala Thr Lys Asp Glu Ser Asp 385 390 395 400
Asn Asp Gin Asn Asn Ala Asn Gin Ala Asn Asn Gin Ala Gin Asn Asn 405 410 415
Gin Asn Gin Gin Gin Ala Asn Gin Asn Gin Gin Gin Gin Gin Gin Arg 420 425 430
Gin Gly Gly Gly Gin Arg His Thr Val Asn Gly Gin Glu Asn Leu Tyr 435 440 445
Arg lie Ala He Gin Tyr Tyr Gly Ser Gly Ser Pro Glu Asn Val Glu 450 455 460
Lys lie Arg Arg Ala Asn Gly Leu Ser Gly Asn Asn He Arg Asn Gly 465 470 475 480
Gin Gin lie Val lie Pro 485
<210〉 23 <211> 472 <212> PRT <213〉葡萄球菌 <400> 23
Met lie Glu Leu lie Lys Met Glu Gly Met He Val Val Ser Asn Asn 15 10 15
Asn Phe Lys Asp Asp Phe Glu Lys Asn Arg Gin Ser He Asn Pro Asp 20 25 30
Glu Gin Gin Thr Glu Leu Lys Glu Asp Asp Lys Thr Asn Glu Asn Lys 35 40 45
Lys Glu Ala Asp Ser Gin Asn Ser Leu Ser Asn Asn Ser Asn Gin Gin 50 55 60
Phe Pro Pro Arg Asn Ala Gin Arg Arg Lys Arg Arg Arg Glu Thr Ala 65 70 75 80
Thr Asn Gin Ser Lys Gin Gin Asp Asp Lys His Gin Lys Asn Ser Asp 85 90 95
Ala Lys Thr Thr Glu Gly Ser Leu Asp Asp Arg Tyr Asp Glu Ala Gin 100 105 110
Leu Gin Gin Gin His Asp Lys Ser Gin Gin Gin Asn Lys Thr Glu Lys 115 120 125
Gin Ser Gin Asp Asn Arg Met Lys Asp Gly Lys Asp Ala Ala He Val 130 135 140
Asn Gly Thr Ser Glu Ser Pro Glu His Lys Ser Lys Ser Thr Gin Asn 145 150 155 160
Arg Pro Gly Pro Lys Ala Gin Gin Gin Lys Arg Lys Ser Glu Ser Thr 165 170 175
Gin Ser Lys Pro Ser Thr Asn Lys Asp Lys Lys Ala Ala Thr Gly Ala 180 185 190
Gly He Ala Gly Ala Ala Gly Val Ala Gly Ala Ala Glu Thr Ser Lys 195 200 205
Arg His His Asn Lys Lys Asp Lys Gin Asp Ser Lys His Ser Asn His 210 215 220
Glu Asn Asp Glu Lys Ser Val Lys Asn Asp Asp Gin Lys Gin Ser Lys 225 230 235 240
Lys Gly Lys Lys Ala Ala Val Gly Ala Gly Ala Ala Ala Gly Val Gly 245 250 255
Ala Ala Gly Val Ala His His Asn Asn Gin Asn Lys His His Asn Glu 260 265 270
Glu Lys Asn Ser Asn Gin Asn Asn Gin Tyr Asn Asp Gin Ser Glu Gly 275 280 285
Lys Lys Lys Gly Gly Phe Met Lys lie Leu Leu Pro Leu lie Ala Ala 290 295 300
He Leu lie Leu Gly Ala lie Ala He Phe Gly Gly Met Ala Leu Asn 305 310 315 320
Asn His Asn Asp Ser Lys Ser Asp Asp Gin Lys He Ala Asn Gin Ser 325 330 335 -54- 119629-序列表.doc 200815028
Lys Lys Asp Ser Asp Lys Lys Asp Gly Ala Gin Ser Glu Asp Asn Lys 340 345 350
Asp Lys Lys Ser Asp Ser Asn Lys Asp Lys Lys Ser Asp Ser Asp Lys 355 360 365
Asn Ala Asp Asp Asp Ser Asp Asn Ser Ser Ser Asn Pro Asn Ala Thr 370 375 380
Ser Thr Asn Asn Asn Asp Asn Val Ala Asn Asn Asn Ser Asn Tyr Thr 385 390 395 400
Asn Gin Asn Gin Gin Asp Asn Ala Asn Gin Asn Ser Asn Asn Gin Gin 405 410 415
Ala Thr Gin Gly Gin Gin Ser His Thr Val Tyr Gly Gin Glu Asn Leu 420 425 430
Tyr Arg lie Ala lie Gin Tyr Tyr Gly Glu Gly Thr Gin Ala Asn Vai 435 440 445
Asp Lys He Lys Arg Ala Asn Gly Leu Ser Ser Asn Asn lie His Asn 450 455 460
Gly Gin Thr Leu Val lie Pro Gin 465 470 <210〉 24 <211〉 165 <212> PRT <213〉葡萄球菌 <400> 24
Met Lys Asn Lys Leu lie Ala Lys Ser Leu Leu Thr He Ala Ala lie 1 5 10 15
Gly lie Thr Thr Thr Thr lie Ala Ser Thr Ala Asp Ala Ser Glu Gly 20 25 30
Tyr Gly Pro Arg Glu Lys Lys Pro Val Ser lie Asn His Asn lie Val 35 40 45
Glu Tyr Asn Asp Gly Thr Fhe Lys Tyr Gin Ser Arg Pro Lys Phe Asn 50 55 60
Ser Thr Pro Lys Tyr lie Lys Phe Lys His Asp Tyr Asn lie Leu Glu 65 70 75 80
Phe Asn Asp Gly Thr Phe Glu Tyr Gly Ala Arg Pro Gin Phe Asn Lys 85 90 95
Fro Ala Ala Lys Thr Asp Ala Thr lie Lys Lys Glu Gin Lys Leu He 100 105 110
Gin Ala Gin Asn Leu Val Arg Glu Phe Glu Lys Thr His Thr Val Ser 115 120 125
Ala His Arg Lys Ala Gin Lys Ala Val Asn Leu Val Ser Phe Glu Tyr 130 135 140
Lys Val Lys Lys Met Val Leu Gin Glu Arg lie Asp Asn Val Leu Lys 145 150 155 160
Gin Gly Leu Val Arg 165 <210〉 25 <211> 319 <212> PRT <213〉葡萄球菌 <400> 25
Met Lys Thr Arg lie Val Ser Ser Val Thr Thr Thr Leu Leu Leu Gly 15 10 15
Ser lie Leu Met Asn Pro Val Ala Asn Ala Ala Asp Ser Asp lie Asn 20 25 30 lie Lys Thr Gly Thr Thr Asp lie Gly Ser Asn Thr Thr Val Lys Thr 35 40 45
Gly Asp Leu Val Thr Tyr Asp Lys Glu Asn Gly Met His Lys Lys Val 50 55 60
Phe Tyr Ser Phe lie Asp Asp Lys Asn His Asn Lys Lys Leu Leu Val 65 70 75 80
He Arg Thr Lys Gly Thr He Ala Gly Gin Tyr Arg Val Tyr Ser Glu 85 90 95
Glu Gly Ala Asn Lys Ser Gly Leu Ala Trp Pro Ser Ala Phe Lys Val 100 105 110
Gin Leu Gin Leu Pro Asp Asn Glu Val Ala Gin lie Ser Asp Tyr Tyr 115 120 125
Pro Arg Asn Ser lie Asp Thr Lys Glu Tyr Met Ser Thr Leu Thr Tyr 130 135 140
Gly Phe Asn Gly Asn Val Thr Gly Asp Asp Thr Gly Lys lie Gly Gly 55- 119629-序列表.doc 200815028 145 150 155 160
Leu lie Gly Ala Asn Val Ser lie Gly His Thr Leu Lys Tyr Val Gin 165 170 175
Pro Asp Phe Lys Thr lie Leu Glu Ser Pro Thr Asp Lys Lys Val Gly 180 185 190
Trp Lys Val lie Phe Asn Asn Met Val Asn Gin Asn Trp Gly Pro Tyr 195 200 205
Asp Arg Asp Ser Trp Asn Pro Val Tyr Gly Asn Gin Leu Phe Met Lys 210 215 220
Thr Arg Asn Gly Ser Met Lys Ala Ala Glu Asn Phe Leu Asp Pro Asn 225 230 235 240
Lys Ala Ser Ser Leu Leu Ser Ser Gly Phe Ser Pro Asp Phe Ala Thr 245 250 255
Val lie Thr Met Asp Arg Lys Ala Ser Lys Gin Gin Thr Asn lie Asp 260 265 270
Val He Tyr Glu Arg Val Arg Asp Asp Tyr Gin Leu His Trp Thr Ser 275 280 285
Thr Asn Trp Lys Gly Thr Asn Thr Lys Asp Lys Trp Thr Asp Arg Ser 290 295 300
Ser Glu Arg Tyr Lys lie Asp Trp Glu Lys Glu Glu Met Thr Asn 305 310 315
<210〉 26 <211> 428 <212> PRT <213〉葡萄球菌 <400> 26
Met His Met Lys Asn Lys Tyr He Ser Lys Leu Leu Val Gly Ala Ala 1 5 10 15
Thr lie Thr Leu Ala Thr Met lie Ser Asn Gly Glu Ala Lys Ala Ser 20 25 30
Glu Asn TKr Gin Gin Thr Ser Thr Lys His Gin Thr Thr Gin Asn Asn 35 40 45
Tyr Val Thr Asp Gin Gin Lys Ala Phe Tyr Gin Val Leu His Leu Lys 50 55 60
Gly lie Thr Glu Glu Gin Arg Asn Gin Tyr lie Lys Thr Leu Arg Glu 65 70 75 80
His Pro Glu Arg Ala Gin Glu Val Phe Ser Glu Ser Leu Lys Asp Ser 85 90 95
Lys Asn Pro Asp Arg Arg Val Ala Gin Gin Asn Ala Phe Tyr Asn Val 100 105 110
Leu Lys Asn Asp Asn Leu Thr Glu Gin Glu Lys Asn Asn Tyr lie Ala 115 120 125
Gin lie Lys Glu Asn Pro Asp Arg Ser Gin Gin Val Trp Val Glu Ser 130 135 140
Val Gin Ser Ser Lys Ala Lys Glu Arg Gin Asn lie Glu Asn Ala Asp 145 150 155 160
Lys Ala lie Lys Asp Phe Gin Asp Asn Lys Ala Pro His Asp Lys Ser 165 170 175
Ala Ala Tyr Glu Ala Asn Ser Lys Leu Pro Lys Asp Leu Arg Asp Lys 180 185 190
Asn Asn Arg Phe Val Glu Lys Val Ser lie Glu Lys Ala He Val Arg 195 200 205
His Asp Glu Arg Val Lys Ser Ala Asn Asp Ala lie Ser Lys Leu Asn 210 215 220
Glu Lys Asp Ser lie Glu Asn Arg Arg Leu Ala Gin Arg Glu Val Asn 225 230 235 240
Lys Ala Pro Met Asp Val Lys Glu His Leu Gin Lys Gin Leu Asp Ala 245 250 255
Leu Val Ala Gin Lys Asp Ala Glu Lys Lys Val Ala Pro Lys Val Glu 260 265 270
Ala Pro Gin lie Gin Ser Pro Gin lie Glu Lys Pro Lys Ala Glu Ser 275 280 285
Pro Lys Val Glu Val Pro Gin Ser Lys Leu Leu Gly Tyr Tyr Gin Ser 290 295 300
Leu Lys Asp Ser Phe Asn Tyr Gly Tyr Lys Tyr Leu Thr Asp Thr Tyr 305 310 315 320
Lys Ser Tyr Lys Glu Lys Tyr Asp Thr Ala Lys Tyr Tyr Tyr Asn Thr 325 330 335
Tyr Tyr Lys Tyr Lys Gly Ala lie Asp Gin Thr Val Leu Thr Val Leu 340 345 350
Gly Ser Gly Ser Lys Ser Tyr lie Gin Pro Leu Lys Val Asp Asp Lys 355 360 365 -56- 119629·序列表.doc 200815028
Asn Gly Tyr Leu Ala Lys Ser Tyr Ala Gin Val Arg Asn Tyr Val Thr 370 375 380
Glu Ser lie Asn Thr Gly Lys Val Leu Tyr Thr Phe Tyr Gin Asn Pro 385 390 395 400
Thr Leu Val Lys Thr Ala lie Lys Ala Gin Glu Thr Ala Ser Ser lie 405 410 415
Lys Asn Thr Leu Ser Asn Leu Leu Ser Phe Trp Lys 420 425
<210〉 27 <211> 350 <212> PRT <213〉葡萄球菌 <400> 27
Met Thr Lys His Tyr Leu Asn Ser 1 5
Ser Ala Met Lys Lys lie Thr Met 20
Ser Leu Val Tyr lie Gly Ala Asp 35 40
Glu Ala Thr Asn Ala Thr Asn Asn 50 55
Thr Ser Gin Pro lie Asn Phe Gin 65 70
Lys Ser His Met Asp Asp Tyr Met 85
Gin Asn Asn Lys Tyr Tyr Phe Gin 100
Trp Lys Glu Tyr Lys Phe Tyr Asn 115 120
Thr Val Val Asn Asp Asn Lys Lys 130 135
Ala Val Glu Pro Gly Tyr Lys Ser 145 150
Val Pro Gin lie Asn Tyr Asn His 165
Glu Lys Ala lie Pro Thr Leu Ala 180
Lys Pro Val Gin Pro Lys Pro Ala 195 200
Thr Lys Pro Val Gin Pro Lys Val 210 215
Thr*Thr Ser Lys Val Glu Asp Asn 225 230
Asp Thr Thr Lys Asp Gin Thr Lys 245
Thr Ala Gin Thr Ala Gin Glu Gin 260
Asp Val Ala Thr Ala Lys Ser Glu 275 280
Asn Lys Ser Gin Gin Thr Asn Lys 290 295
Lys Gin Ala Ser Lys Ala Lys Glu 305 310
Val Asp Asn Phe lie Ser Thr Val 325
Gly Ser Leu Ser Leu Leu Leu Phe 340
Lys Tyr Gin Ser Glu Gin Arg Ser 10 15
Gly Thr Ala Ser lie lie Leu Gly 25 30
Ser Gin Gin Val Asn Ala Ala Thr 45
Gin Ser Thr Gin Val Ser Gin Ala 60
Val Gin Lys Asp Gly Ser Ser Glu 75 80
Gin His Pro Gly Lys Val He Lys 90 95
Thr Val Leu Asn Asn Ala Ser Phe 105 110
Ala Asn Asn Gin Glu Leu Ala Thr 125
Ala Asp Thr Arg Thr He Asn Val 140
Leu Thr Thr Lys Val His He Val 155 160
Arg Tyr Thr Thr His Leu Glu Phe 170 175
Asp Ala Ala Lys Pro Asn Asn Val 185 190
Gin Pro Lys Thr Pro Thr Glu Gin 205
Glu Lys Val Lys Pro Thr Val Thr 220
His Ser Thr Lys Val Val Ser Thr 235 240
Thr Gin Thr Ala His Thr Val Lys 250 255
Asn Lys Val Gin Thr Pro Val Lys 265 270
Ser Asn Asn Gin Ala Val Ser Asp 285
Val Thr Lys His Asn Glu Thr Pro 300
Leu Pro Lys Thr Gly Leu Thr Ser 315 320
Ala Phe Ala Thr Leu Ala Leu Leu 330 335
Lys Arg Lys Glu Ser Lys 345 350 <210> 28 <211〉 645 <212> PRT <213〉葡萄球菌 <400> 28
Met Asn Lys Gin Gin Lys Glu Phe Lys Ser Phe Tyr Ser He Arg Lys 15 10 15
Ser Ser Leu Gly Val Ala Ser Val Ala lie Ser Thr Leu Leu Leu Leu 20 25 30
Met Ser Asn Gly Glu Ala Gin Ala Ala Ala Glu Glu Thr Gly Gly Thr 35 40 45
Asn Thr Glu Ala Gin Pro Lys Thr Glu Ala Val Ala Ser Pro Thr Thr 57- 119629-序列表.doc 200815028 50 55 60
Thr Ser Glu Lys Ala Pro Glu Thr Lys Pro Val Ala Asn Ala Val Ser 65 70 75 80
Val Ser Asn Lys Glu Val Glu Ala Pro Thr Ser Glu Thr Lys Glu Ala 85 90 95
Lys Glu Val Lys Glu Val Lys Ala Pro Lys Glu Thr Lys Ala Val Lys 100 105 110
Pro Ala Ala Lys Ala Thr Asn Asn Thr Tyr Fro lie Leu Asn Gin Glu 115 120 125
Leu Arg Glu Ala He Lys Asn Pro Ala He Lys Asp Lys Asp His Ser 130 135 140
Ala Pro Asn Ser Arg Pro lie Asp Phe Glu Met Lys Lys Glu Asn Gly 145 150 155 160
Glu Gin Gin Phe Tyr His Tyr Ala Ser Ser Val Lys Pro Ala Arg Val 165 170 175
He Phe Thr Asp Ser Lys Pro Glu lie Glu Leu Gly Leu Gin Ser Gly 180 185 190
Gin Phe Trp Arg Lys Phe Glu Val Tyr Glu Gly Asp Lys Lys Leu Pro 195 200 205
He Lys Leu Val Ser Tyr Asp Thr Val Lys Asp Tyr Ala Tyr lie Arg 210 215 220
Phe Ser Val Ser Asn Gly Thr Lys Ala Val Lys lie Val Ser Ser Thr 225 230 235 240
His Phe Asn Asn Lys Glu Glu Lys Tyr Asp Tyr Thr Leu Met Glu Phe 245 250 255
Ala Gin Pro lie Tyr Asn Ser Ala Asp Lys Phe Lys Thr Glu Glu Asp 260 265 270
Tyr Lys Ala Glu Lys Leu Leu Ala Pro Tyr Lys Lys Ala Lys Thr Leu 275 280 285
Glu Arg Gin Val Tyr Glu Leu Asn Lys lie Gin Asp Lys Leu Pro Glu 290 295 300
Lys Leu Lys Ala Glu Tyr Lys Lys Lys Leu Glu Asp Thr Lys Lys Ala 305 310 315 320
Leu Asp Glu Gin Val Lys Ser Ala lie Thr Glu Phe Gin Asn Val Gin 325 330 335
Pro Thr Asn Glu Lys Met Thr Asp Leu Gin Asp Thr Lys Tyr Val Val 340 345 350
Tyr Glu Ser Val Glu Asn Asn Glu Ser Met Met Asp Thr Fhe Val Lys 355 360 365
His Pro He Lys Thr Gly Met Leu Asn Gly Lys Lys Tyr Met Val Met 370 375 380
Glu Thr Thr Asn Asp Asp Tyr Trp Lys Asp Phe Met Val Glu Gly Gin 385 390 395 400
Arg Val Arg Thr lie Ser Lys Asp Ala Lys Asn Asn Thr Arg Thr lie 405 410 415 lie Phe Pro Tyr Val Glu Gly Lys Thr Leu Tyr Asp Ala lie Val Lys 420 425 430
Val His Val Lys Thr lie Asp Tyr Asp Gly Gin Tyr His Val Arg lie 435 440 445
Val Asp Lys Glu Ala Phe Thr Lys Ala Asn Thr Asp Lys Ser Asn Lys 450 455 460
Lys Glu Gin Gin Asp Asn Ser Ala Lys Lys Glu Ala Thr Pro Ala Thr 465 470 475 480
Pro Ser Lys Pro Thr Pro Ser Pro Val Glu Lys Glu Ser Gin Lys Gin 485 490 495
Asp Ser Gin Lys Asp Asp Asn Lys Gin Leu Pro Ser Val Glu Lys Glu 500 505 510
Asn Asp Ala Ser Ser Glu Ser Gly Lys Asp Lys Thr Pro Ala Thr Lys 515 520 525
Pro Thr Lys Gly Glu Val Glu Ser Ser Ser Thr Thr Pro Thr Lys Val 530 535 540
Val Ser Thr Thr Gin Asn Val Ala Lys Pro Thr Thr Ala Ser Ser Lys 545 550 555 560
Thr Thr Lys Asp Val Val Gin Thr Ser Ala Gly Ser Ser Glu Ala Lys 565 570 575
Asp Ser Ala Pro Leu Gin Lys Ala Asn lie Lys Asn Thr Asn Asp Gly 580 585 590
His Thr Gin Ser Gin Asn Asn Lys Asn Thr Gin Glu Asn Lys Ala Lys 595 600 605
Ser Leu Pro Gin Thr Gly Glu Glu Ser Asn Lys Asp Met Thr Leu Pro 610 615 620
Leu Met Ala Leu Leu Ala Leu Ser Ser lie Val Ala Phe Val Leu Pro 625 630 635 640
Arg Lys Arg Lys Asn 645 58- 119629-序列表.doc 200815028 <2I0> 29 <211> 953 <212〉 PRT <213〉葡鏡菌 <400〉 29
Met Asn Asn Lys Lys Thr Ala Thr Asn Arg Lys Gly Met lie Pro Asn 1 5 10 15
Arg Leu Asn Lys Phe Ser lie Arg Lys Tyr Ser Val Gly Thr Ala Ser 20 25 30 lie Leu Val Gly Thr Thr Leu lie Phe Gly Leu Ser Gly His Glu Ala 35 40 45
Lys Ala Ala Glu His Thr Asn Gly Glu Leu Asn Gin Ser Lys Asn Glu 50 55 60
Thr Thr Ala Pro Ser Glu Asn Lys Thr Thr Glu Lys Val Asp Ser Arg 65 70 75 80
Gin Leu Lys Asp Asn Thr Gin Thr Ala Thr Ala Asp Gin Pro Lys Val 85 90 95
Thr Met Ser Asp Ser Ala Thr Val Lys Glu Thr Ser Ser Asn Met Gin 100 105 110
Ser Pro Gin Asn Ala Thr Ala Ser Gin Ser Thr Thr Gin Thr Ser Asn 115 120 125
Val Thr Thr Asn Asp Lys Ser Ser Thr Thr Tyr Ser Asn Glu Thr Asp 130 135 140
Lys Ser Asn Leu Thr Gin Ala Lys Asn Val Ser Thr Thr Fro Lys Thr 145 150 155 160
Thr Thr lie Lys Gin Arg Ala Leu Asn Arg Met Ala Val Asn Thr Val 165 170 175
Ala Ala Pro Gin Gin Gly Thr Asn Val Asn Asp Lys Val His Phe Thr 180 185 190
Asn He Asp lie Ala He Asp Lys Gly His Val Asn Lys Thr Thr Gly 195 200 205
Asn Thr Glu Phe Trp Ala Thr Ser Ser Asp Val Leu Lys Leu Lys Ala 210 215 220
Asn Tyr Thr He Asp Asp Ser Vai Lys Glu Gly Asp Thr Phe Thr Phe 225 230 235 240
Lys Tyr Gly Gin Tyr Phe Arg Pro Gly Ser Val Arg Leu Pro Ser Gin 245 250 255
Thr Gin Asn Leu Tyr Asn Ala Gin Gly Asn He He Ala Lys* Gly lie 260 265 270
Tyr Asp Ser Lys Thr Asn Thr Thr Thr Tyr Thr Phe Thr Asn Tyr Val 275 280 285
Asp Gin Tyr Thr Asn Val Ser Gly Ser Phe Glu Gin Val Ala Phe Ala 290 295 300
Lys Arg Glu Asn Ala Thr Thr Asp Lys Thr Ala Tyr Lys Met Glu Val 305 310 315 320
Thr Leu Gly Asn Asp Thr Tyr Ser Lys Asp Val lie Val Asp Tyr Gly 325 330 335
Asn Gin Lys Gly Gin Gin Leu He Ser Ser Thr Asn Tyr lie Asn Asn 340 345 350
Glu Asp Leu Ser Arg Asn Met Thr Val Tyr Val Asn Gin Pro Lys Lys 355 360 365
Thr Tyr Thr Lys Glu Thr Phe Val Thr Asn Leu Thr Gly Tyr Lys Phe 370 375 380
Asn Pro Asp Ala Lys Asn Phe Lys lie Tyr Glu Val Thr Asp Gin Asn 385 390 395 400
Gin Phe Val Asp Ser Phe Thr Pro Asp Thr Ser Lys Leu Lys Asp Val 405 410 415
Thr Gly Gin Phe Asp Val lie Tyr Ser Asn Asp Asn Lys Thr Ala Thr 420 425 430
Val Asp Leu Leu Asn Gly Gin Ser Ser Ser Asp Lys Gin Tyr He lie 435 440 445
Gin Gin Val Ala Tyr Pro Asp Asn Ser Ser Thr Asp Asn Gly Lys lie 450 455 460
Asp Tyr Thr Leu Glu Thr Gin Asn Gly Lys Ser Ser Trp Ser Asn Ser 465 470 475 480
Tyr Ser Asn Val Asn Gly Ser Ser Thr Ala Asn Gly Asp Gin Lys Lys 485 490 495
Tyr Asn Leu Gly Asp Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Lys 500 505 510
Gin Asp Ala Asn Glu Lys Gly lie Lys Gly Val Tyr Val lie Leu Lys 515 520 525
Asp Ser Asn Gly Lys Glu Leu Asp Arg Thr Thr Thr Asp Glu Asn Gly 59- 119629-序列表.doc 200815028 530 535 540
Lys Tyr Gin Phe Thr Gly Leu Ser Asn Gly Thr Tyr Ser Val Glu Phe 545 550 555 560
Ser Thr Pro Ala Gly Tyr Thr Pro Thr Thr Ala Asn Ala Gly Thr Asp 565 570 575
Asp Ala Val Asp Ser Asp Gly Leu Thr Thr Thr Gly Val lie Lys Asp 580 585 590
Ala Asp Asn Met Thr Leu Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr 595 600 605
Ser Leu Gly Asp Tyr Val 了rp Tyr Asp Ser Asn Lys Asp Gly Lys Gin 610 615 620
Asp Ser Thr Glu Lys Gly lie Lys Gly Val Lys Val Thr Leu Gin Asn 625 630 635 640
Glu Lys Gly Glu Val lie Gly Thr Thr Glu Thr Asp Glu Asn Gly Lys 645 650 655
Tyr Arg Phe Asp Asn Leu Asp Ser Gly Lys Tyr Lys Val lie Fhe Glu 660 665 670
Lys Pro Ala Gly Leu Thr Gin Thr Gly Thr Asn Thr Thr Glu Asp Asp 675 680 685
Lys Asp Ala Asp Gly Gly Glu Val Asp Val Thr lie Thr Asp His Asp 690 695 700
Asp Phe Thr Leu Asp Asn Gly Tyi: Tyr Glu Glu Glu Thr Ser Asp Ser 705 710 715 720
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 725 730 735
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 740 745 750
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 755 760 765
Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 770 775 780
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 785 790 795 800
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 805 810 815
Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Ser Asp Ser Asp Ser 820 825 830
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 835 840 845
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 850 855 860
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 865 870 875 880
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys 885 890 895
His Thr Pro Thr Lys Pro Met Ser Thr Val Lys Asp Gin His Lys Thr 900 905 910
Ala Lys Ala Leu Pro Glu Thr Gly Ser Glu Asn Asn Asn Ser Asn Asn 915 920 925
Gly Thr Leu Phe Gly Gly Leu Phe Ala Ala Leu Gly Ser Leu Leu Leu 930 935 940
Phe Gly Arg Arg Lys Lys Gin Asn Lys 945 950
<210〉 30 <211〉 935 <212〉 PRT ⑽葡萄球菌 <400〉 30
Met Asn Met Lys Lys Lys Glu Lys His Ala lie Arg Lys Lys Ser lie 1 5 10 15
Gly Val Ala Ser Val Leu Val Gly Thr Leu lie Gly Phe Gly Leu Leu 20 25 30
Ser Ser Lys Glu Ala Asp Ala Ser Glu Asn Ser Val Thr Gin Ser Asp 35 40 45
Ser Ala Ser Asn Glu Ser Lys Ser Asn Asp Ser Ser Ser Val Ser Ala 50 55 60
Ala Pro Lys Thr Asp Asp Thr Asn Val Ser Asp Thr Lys Thr Ser Ser 65 70 75 80
Asn Thr Asn Asn Gly Glu Thr Ser Val Ala Gin Asn Pro Ala Gin Gin 85 90 95
Glu Thr Thr Gin Ser Ser Ser Thr Asn Ala Thr Thr Glu Glu Thr Pro 100 105 110 -60 - 119629·序列表.doc 200815028
Val Thr Gly Glu Ala Thr Thr Thr Thr Thr Asn Gin Ala Asn Thr Pro 115 120 125
Ala Thr Thr Gin Ser Ser Asn Thr Asn Ala Glu Glu Leu Val Asn Gin 130 135 140
Thr Ser Asn Glu Thr Thr Ser Asn Asp Thr Asn Thr Val Ser Ser Val 145 150 155 160
Asn Ser Pro Gin Asn Ser Thr Asn Ala Glu Asn Val Ser Thr Thr Gin 165 170 175
Asp Thr Ser Thr Glu Ala Thr Pro Ser Asn Asn Glu Ser Ala Pro Gin 180 185 190
Asn Thr Asp Ala Ser Asn Lys Asp Val Val Ser Gin Ala Val Asn Pro 195 200 205
Ser Thr Pro Arg Met Arg Ala Phe Ser Leu Ala Ala Val Ala Ala Asp 210 215 220
Ala Pro Ala Ala Gly Thr Asp lie Thr Asn Gin Leu Thr Asp Val Lys 225 230 235 240
Val Thr lie Asp Ser Gly Thr Thr Val Tyr Pro His Gin Ala Gly Tyr 245 250 255
Val Lys Leu Asn Tyr Gly Fhe Ser Val Pro Asn Ser Ala Val Lys Gly 260 265 270
Asp Thr Phe Lys lie Thr Val Pro Lys Glu Leu Asn Leu Asn Gly Val 275 280 285
Thr Ser Thr Ala Lys Val Pro Pro lie Met Ala Gly Asp Gin Val Leu 290 295 300
Ala Asn Gly Val lie Asp Ser Asp Gly Asn Val He Tyr Thr Phe Thr 305 310 315 320
Asp Tyr Val Asp Asn Lys Glu Asn Val Thr Ala Asn lie Thr Met Pro 325 330 335
Ala Tyr He Asp Pro Glu Asn Val Thr Lys Thr Gly Asn Val Thr Leu 340 345 350
Thr Thr Gly lie Gly Thr Asn Thr Ala Ser Lys Thr Val Leu lie Asp 355 360 365
Tyr Glu Lys Tyr Gly Gin Phe His Asn Leu Ser lie Lys Gly Thr lie 370 375 380
Asp Gin lie Asp Lys Thr Asn Asn Thr Tyr Arg Gin Thr lie Tyr Val 385 390 395 400
Asn Pro Ser Gly Asp Asn Val Val Leu Pro Ala Leu Thr Gly Asn Leu 405 410 415 lie Pro Asn Thr Lys Ser Asn Ala Leu lie Asp Ala Lys Asn Thr Asp 420 425 430 lie Lys Val Tyr Arg Val Asp Asn Ala Asn Asp Leu Ser Glu Ser Tyr 435 440 445
Tyr Val Asn Pro Ser Asp Phe Glu Asp Val Thr Asn Gin Val Arg lie 450 455 460
Ser Phe Pro Asn Ala Asn Gin Tyr Lys Val Glu Phe Pro Thr Asp Asp 465 470 475 480
Asp Gin lie Thr Thr Pro Tyr lie Val Val Val Asn Gly His lie Asp 485 490 495
Pro Ala Ser Thr Gly Asp Leu Ala Leu Arg Ser Thr Phe Tyr Gly Tyr 500 505 510
Asp Ser Asn Phe lie Trp Arg Ser Met Ser Trp Asp Asn Glu Val Ala 515 520 525
Phe Asn Asn Gly Ser Gly Ser Gly Asp Giy lie Asp Lys Pro Val Val 530 535 540
Pro Glu Gin Pro Asp Glu Pro Gly Glu lie Glu Pro lie Pro Glu Asp 545 550 555 560
Ser Asp Ser Asp Pro Gly Ser Asp Ser Gly Ser Asp Ser Asn Ser Asp 565 570 575
Ser Gly Ser Asp Ser Gly Ser Asp Ser Thr Ser Asp Ser Gly Ser Asp -580 585 590
Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp 595 600 605
Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala 610 615 620
Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp 625 630 635 640
Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp 645 650 655
Ser Asp Ser Ala Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp Ser Asp 660 665 670
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 675 680 685
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 690 695 700
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 61- 119629·序列表.doc 200815028 705 710 715 720
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 725 730 735
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 740 745 750
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala 755 760 765
Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp 770 775 780
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp 785 790 795 800
Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp 805 810 815
Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Ala Ser Asp Ser Asp 820 825 830
Ser Gly Ser Asp Ser Asp Ser Ser Ser Asp Ser Asp Ser Asp Ser Thr 835 840 845
Ser Asp Thr Gly Ser Asp Asn Asp Ser Asp Ser Asp Ser Asn Ser Asp 850 855 860
Ser Glu Ser Gly Ser Asn Asn Asn Val Val Pro Pro Asn Ser Pro Lys 865 870 875 880
Asn Gly Thr Asn Ala Ser Asn Lys Asn Glu Ala Lys Asp Ser Lys Glu 885 890 895
Pro Leu Pro Asp Thr Gly Ser Glu Asp Glu Ala Asn Thr Ser Leu lie 900 905 910
Trp Gly Leu Leu Ala Ser Leu Gly Ser Leu Leu Leu Fhe Arg Arg Lys
915 920 925
Lys Glu Asn Lys Asp Lys Lys 930 935 <210〉 31 <211> 1038 <212> PRT <213〉葡萄球菌 <400> 31
Met Lys Asn Asn Leu Arg Tyr Gly He Arg Lys His Lys Leu Gly Ala 15 10 15
Ala Ser Val Fhe Leu Gly Thr Met He Val Val Gly Met Gly Gin Asp 20 25 30
Lys Glu Ala Ala Ala Ser Glu Gin Lys Thr Thr Thr Val Glu Glu Asn 35 40 45
Gly Asn Ser Ala Thr Asp Asn Lys Thr Ser Glu Thr Gin Thr Thr Ala 50 55 60
Thr Asn Val Asn His lie Glu Glu Thr Gin Ser Tyr Asn Ala Thr Val 65 70 75 80
Thr Glu Gin Pro Ser Asn Ala Thr Gin Vai Thr Thr Glu Glu Ala Pro 85 90 95
Lys Ala Val Gin Ala Pro Gin Thr Ala Gin Pro Ala Asn Val Glu Thr 100 105 110
Val Lys Glu Glu Glu Lys Pro Gin Val Lys Glu Thr Thr Gin Pro Gin 115 120 125
Asp Asn Ser Gly Asn Gin Arg Gin Val Asp Leu Thr Pro Lys Lys Val 130 135 140
Thr Gin Asn Gin Gly Thr Glu Thr Gin Val Glu Val Ala Gin Pro Arg 145 150 155 160
Thr Ala Ser Glu Ser Lys Pro Arg Val Thr Arg Ser Ala Asp Val Ala 165 170 175
Glu Ala Lys Glu Ala Ser Asp Val Ser Glu Val Lys Gly Thr Asp Val 180 185 190
Thr Ser Lys Val Thr Val Glu Ser Gly Ser lie Glu Ala Pro Gin Gly 195 200 205
Asn Lys Val Glu Pro His Ala Gly Gin Arg Val Val Leu Lys Tyr Lys 210 215 220
Leu Lys Phe Ala Asp Gly Leu Lys Arg Gly Asp Tyr Phe Asp Phe Thr 225 230 235 240
Leu Ser Asn Asn Val Asn Thr Tyr Gly Val Ser Thr Ala Arg Lys Val 245 250 255
Pro Glu lie Lys Asn Gly Ser Val Val Met Ala Thr Gly Glu He Leu 260 265 270
Gly Asn Gly Asn lie Arg Tyr Thr Phe Thr Asn Glu lie Glu His Lys 275 280 285
Val Glu Val Thr Ala Asn Leu Glu lie Asn Leu Phe lie Asp Pro Lys 290 295 300 -62- 119629-序列表.doc 200815028
Thr Val Gin Ser Asn Gly Glu Gin Lys lie Thr Ser Lys Leu Asn Gly 305 3l5 315 320
Glu Glu Thr Glu Lys Thr lie Pro Val Val Tyr Asn Pro Gly Val Ser 325 330 335
Asn Ser Tyr Thr Asn Val Asn Gly Ser lie Glu Thr Phe Asn Lys Glu 340 345 350
Ser Asn Lys Phe Thr His He Ala Tyr lie Lys Pro Met Asn Gly Asn 355 360 365
Gin Ser Asn Thr Val Ser Val Thr Gly Thr Leu Thr Glu Gly Ser Asn 370 375 380
Leu Ala Gly Gly Gin Pro Thr Val Lys Val Tyr Glu Tyr Leu Gly Lys 385 390 395 400
Lys Asp Glu Leu Pro Gin Ser Val Tyr Ala Asn Thr Ser Asp Thr Asn 405 410 415
Lys Phe Lys Asp Val Thr Lys Glu Met Asn Gly Lys Leu Ser Val Gin 420 425 430
Asp Asn Gly Ser Tyr Ser Leu Asn Leu Asp Lys Leu Asp Lys Thr Tyr 435 440 445
Val lie His Tyr Thr Gly Glu Tyr Leu Gin Gly Ser Asp Gin Val Asn 450 455 460
Phe Arg Thr Glu Leu Tyr Gly Tyr Pro Glu Arg Ala Tyr Lys Ser Tyr 465 470 475 480
Tyr Val Tyr Gly Gly Tyr Arg Leu Thr Trp Asp Asn Gly Leu Val Leu 485 490 495
Tyr Ser Asn Lys Ala Asp Gly Asn Gly Lys Asn Gly Gin lie lie Gin 500 505 510
Asp Asn Asp Phe Glu Tyr Lys Glu Asp Thr Ala Lys Gly Thr Met Ser 515 520 525
Gly Gin Tyr Asp Ala Lys Gin lie lie Glu Thr Glu Glu Asn Gin Asp 530 535 540
Asn Thr Pro Leu Asp lie Asp Tyr His Thr Ala lie Asp Gly Glu Gly 545 550 555 560
Gly Tyr Val Asp Gly Tyr lie Glu Thr lie Glu Glu Thr Asp Ser Ser 565 570 575
Ala lie Asp lie Asp Tyr His Thr Ala Val Asp Ser Glu Val Gly His 580 585 590
Val Gly Gly Tyr Thr Glu Ser Ser Glu Glu Ser Asn Pro lie Asp Phe 595 600 605
Glu Glu Ser Thr His Glu Asn Ser Lys His His Ala Asp Val Val Glu 610 615 620
Tyr Glu Glu Asp Thr Asn Pro Gly Gly Gly Gin Val Thr Thr Glu Ser 625 630 635 640
Asn Leu Val Glu Phe Asp Glu Glu Ser Thr Lys Gly lie Val Thr Gly 645 650 655
Ala Val Ser Asp His Thr Thr lie Glu Asp Thr Lys Glu Tyr Thr Thr 660 665 670
Glu Ser Asn Leu lie Glu Leu Val Asp Glu Leu Pro Glu Glu His Gly 675 680 685
Gin Ala Gin Gly Pro lie Glu Glu lie Thr Glu Asn Asn His His lie 690 695 700
Ser His Ser Gly Leu Gly Thr Giu Asn Gly His Gly Asn Tyr Gly Val 705 710 715 720 lie Glu Glu lie Glu Glu Asn Ser His Val Asp lie Lys Ser Glu Leu 725 730 735
Gly Tyr Glu Gly Gly Gin Asn Ser Gly Asn Gin Ser Phe Glu Glu Asp 740 745 750
Thr Glu Glu Asp Lys Pro Lys Tyr Glu Gin Gly Gly Asn lie Val Asp 755 760 765 lie Asp Phe Asp Ser Val Pro Gin lie His Gly Gin Asn Lys Gly Asp 770 775 780
Gin Ser Phe Glu Glu Asp Thr Glu Lys Asp Lys Pro Lys Tyr Glu His 785 790 795 800
Gly Gly Asn lie lie Asp lie Asp Phe Asp Ser Val Pro Gin lie His 805 810 815
Gly Phe Asn Lys His Asn Glu He lie Glu Glu Asp Thr Asn Lys Asp 820 825 830
Lys Pro Asn Tyr Gin Phe Gly Gly His Asn Ser Val Asp Phe Glu Glu 835 840 845
Asp Thr Leu Pro Lys Val Ser Gly Gin Asn Glu Gly Gin Gin Thr lie 850 855 860
Glu Glu Asp Thr Thr Pro Pro Thr Pro Pro Thr Pro Glu Val Pro Ser 865 870 875 880
Glu Pro Glu Thr Pro Met Pro Pro Thr Pro Glu Val Pro Ser Glu Pro 885 890 895
Glu Thr Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr 63- 119629·序列表.doc 200815028 900 905 910
Pro Thr Fro Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr Pro Thr 915 920 925
Fro Pro Thr Pro Glu Val Pro Ser Glu Pro Glu Thr Pro Thr Pro Pro 930 935 940
Thr Pro Glu Val Pro Ala Glu Pro Gly Lys Pro Val Pro Pro Ala Lys 945 950 955 960
Glu Glu Pro Lys Lys Pro Ser Lys Pro Val Giu Gin Gly Lys Val Val 965 970 975
Thr Fro Val He Glu lie Asn Glu Lys Val Lys Ala Val Ala Pro Thr 980 985 990
Lys Lys Ala Gin Ser Lys Lys Ser Glu Leu Pro Glu Thr Gly Gly Glu 995 1000 1005
Glu Ser Thr Asn Lys Gly Met Leu Phe Gly Gly Leu Phe Ser lie Leu 1010 1015 1020
Gly Leu Ala Leu Leu Arg Arg Asn Lys Lys Asn Asn Lys Ala 1025 1030 1035 <210> 32 <211> 877 <212> PRT <213〉葡萄球菌 <400> 32
Met Lys Lys Arg lie Asp Tyr Leu Ser Asn Lys Gin Asn Lys Tyr Ser 1 5 10 15 lie Arg Arg Phe Thr Val Gly Thr Thr Ser Val He Val Gly Ala Thr 20 25 30
He Leu Phe Gly lie Gly Asn His Gin Ala Gin Ala Ser Glu Gin Ser 35 40 45
Asn Asp Thr Thr Gin Ser Ser Lys Asn Asn Ala Ser Ala Asp Ser Glu 50 55 60
Lys Asn Asn Uet He Glu TKr Pro Gin Leu Asn Thr Tl^r Ala Asn Asp 65 70 75 80
Thr Ser Asp lie Ser Ala Asn Thr Asn Ser Ala Asn Val Asp Ser Thr 85 90 95
Thr Lys Pro Met Ser Thr Gin Thr Ser Asn Thr Thr Thr Thr Glu Pro 100 105 110
Ala Ser Thr Asn Glu Thr Pro Gin Pro Thr Ala lie Lys Asn Gin Ala 115 120 125
Thr Ala Ala Lys Met Gin Asp Gin Thr Val Pro Gin Glu Ala Asn Ser 130 135 140
Gin Val Asp Asn Lys Thr Thr Asn Asp Ala Asn Ser lie Ala Thr Asn 145 150 155 160
Ser Glu Leu Lys Asn Ser Gin Thr Leu Asp Leu Pro Gin Ser Ser Pro 165 170 175
Gin Thr lie Ser Asn Ala Gin Gly Thr Ser Lys Pro Ser Val Arg Thr 180 185 190
Arg Ala Val Arg Ser Leu Ala Val Ala Glu Pro Val Val Asn Ala Ala 195 200 205
Asp Ala Lys Gly Thr Asn Val Asn Asp Lys Val Thr Ala Ser Asn Phe 210 215 220
Lys Leu Glu Lys Thr Thr Phe Asp Pro Asn Gin Ser Gly Asn Thr Phe 225 230 235 240
Met Ala Ala Asn Phe Thr Val Thr Asp Lys Val Lys Ser Gly Asp Tyr 245 250 255
Phe Thr Ala Lys Leu Pro Asp Ser Leu Thr Gly Asn Gly Asp Val Asp 260 265 270
Tyr Ser Asn Ser Asn Asn Thr Met Pro lie Ala Asp lie Lys Ser Thr 275 280 285
Asn Gly Asp Val Val Ala Lys Ala Thr Tyr Asp lie Leu Thr Lys Thr 290 295 300
Tyr Thr Phe Val Phe Thr Asp Tyr Val Asn Asn Lys Glu Asn lie Asn 305 310 315 320
Gly Gin Phe Ser Leu Pro Leu Phe Thr Asp Arg Ala Lys Ala Pro Lys 325 330 335
Ser Gly Thr Tyr Asp Ala Asn lie Asn lie Ala Asp Glu Met Phe Asn 340 345 350
Asn Lys lie Thr Tyr Asn Tyr Ser Ser Pro lie Ala Gly lie Asp Lys 355 360 365
Pro Asn Gly Ala Asn lie Ser Ser Gin He He Gly Val Asp Thr Ala 370 375 380
Ser Gly Gin Asn Thr Tyr Lys Gin Thr Val Phe Val Asn Pro Lys Gin 385 390 395 400 64- 119629-序列表.doc 200815028
Arg Val Leu Gly Asn Thr Trp Val Tyr He Lys Gly Tyr Gin Asp Lys 405 410 415
He Glu Glu Ser Ser Gly Lys Val Ser Ala Thr Asp Thr Lys Leu Arg 420 425 430 lie Phe Glu Val Asn Asp Thr Ser Lys Leu Ser Asp Ser Tyr Tyr Ala 435 440 445
Asp Pro Asn Asp Ser Asn Leu Lys Glu Val Thr Asp Gin Phe Lys Asn 450 455 460
Arg lie Tyr Tyr Glu His Pro Asn Val Ala Ser He Lys Phe Gly Asp 465 470 475 480
He Thr Lys Thr Tyr Val Val Leu Val Glu Gly His Tyr Asp Asn Thr 485 490 495
Gly Lys Asn Leu Lys Thr Gin Val lie Gin Glu Asn Val Asp Pro Val 500 505 510
Thr Asn Arg Asp Tyr Ser lie Phe Gly Trp Asn Asn Glu Asn Val Val 515 520 525
Arg Tyr Gly Gly Gly Ser Ala Asp Gly Asp Ser Ala Val Asn Fro Lys 530 535 540
Asp Pro Thr Pro Gly Pro Pro Val Asp Pro Glu Pro Ser Pro Asp Pro 545 550 555 560
Glu Pro Glu Pro Thr Pro Asp Pro Glu Pro Ser Pro Asp Pro Glu Pro 565 570 575
Glu Pro Ser Pro Asp Pro Asp Pro Asp Ser Asp Ser Asp Ser Asp Ser 580 585 590
Gly Ser Asp Ser Asp Ser Gly Ser Asp Ser Asp Ser Glu Ser Asp Ser 595 600 605
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser 610 615 620
Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 625 630 635 640
Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser 645 650 655
Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Glu Ser 660 665 670
Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 675 680 685
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 690 695 700
Asp Ser Asp Ser Asp Ser Asp Ser Glu Ser Asp Ser Asp Ser Asp Ser 705 710 715 720
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Sex Asp Ser Asp Ser 725 730 735
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 740 745 750
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 755 760 765
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 770 775 780
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 785 790 795 800
Asp Ser Asp Ser Arg Val Thr Pro Pro Asn Asn Glu Gin Lys Ala Pro 805 810 815
Ser Asn Pro Lys Gly Glu Val Asn His Ser Asn Lys Val Ser Lys Gin 820 825 830
His Lys Thr Asp Ala Leu Pro Glu Thr Gly Asp Lys Ser Glu Asn Thr 835 840 845
Asn Ala Thr Leu Phe Gly Ala Met Met Ala Leu Leu Gly Ser Leu Leu 850 855 860
Leu Phe Arg Lys Arg Lys Gin Asp His Lys Glu Lys Ala 865 870 875 <210〉 33 <211〉 658 <212〉 PRT <213〉葡萄球菌 <400> 33
Met Lys Lys Gin lie lie Ser Leu Gly Ala Leu Ala Val Ala Ser Ser 1 5 10 15
Leu Phe Thr Trp Asp Asn Lys Ala Asp Ala He Val Thr Lys Asp Tyr 20 25 30
Ser Lys Glu Ser Arg Val Asn Glu Lys Ser Lys Lys Gly Ala Thr Val 35 40 45
Ser Asp Tyr Tyr Tyr Trp Lys lie He Asp Ser Leu Glu Ala Gin Phe 65- 119629-序列表.doc 200815028 50 55 60
Thr Gly Ala lie Asp Leu Leu Glu Asp Tyr Lys Tyr Gly Asp Pro lie 65 70 75 80
Tyr Lys Glu Ala Lys Asp Arg Leu Met Thr Arg Val Leu Gly Glu Asp 85 90 95
Gin Tyr Leu Leu Lys Lys Lys Ι1θ Asp Giu Tyr Glu Leu Tyr Lys Lys 100 105 110
Trp Tyr Lys Ser Ser Asn Lys Asn Thr Asn Met Leu Thr Fhe His Lys 115 120 125
Tyr Asn Leu Tyr Asn Leu Thr Met Asn Glu Tyr Asn Asp lie Phe Asn 130 135 140
Ser Leu Lys Asp Ala Val Tyr Gin Phe Asn Lys Glu Val Lys Glu He 145 150 155 160
Glu His Lys Asn Val Asp Leu Lys Gin Phe Asp Lys Asp Gly Giu Asp 165 170 175
Lys Ala Thr Lys Glu Val Tyr Asp Leu Val Ser Glu lie Asp Thr Leu 180 185 190
Val Val Thr Tyr Tyr Ala Asp Lys Asp Tyr Gly Glu His Ala Lys Glu 195 200 205
Leu Arg Ala Lys Leu Asp Leu lie Leu Gly Asp Thr Asp Asn Pro His 210 215 220
Lys lie Thr Asn Glu Arg lie Lys Lys Glu Met lie Asp Asp Leu Asn 225 230 235 240
Ser lie lie Asp Asp Phe Phe Met Glu Thr Lys Gin Asn Arg Pro Asn 245 250 255
Ser lie Thr Lys Tyr Asp Pro Thr Lys His Asn Phe Lys Glu Lys Ser 260 265 270
Glu Asn Lys Pro Asn Phe Asp Lys Leu Val Glu Glu Thr Lys Lys Ala 275 280 285
Val Lys Glu Ala Asp Glu Ser Trp Lys Asn Lys Thr Val Lys Lys Tyr 2Q〇 295 300
Glu Glu Thr Val Thr Lys Ser Pro Val Val Lys Glu Glu Lys Lys Val 305 310 315 320
Glu Glu Pro Gin Leu Pro Lys Val Gly Asn Gin Gin Glu Val Lys Thr 325 330 335
Thr Ala Gly Lys Ala Glu Glu Thr Thr Gin Pro Val Ala Gin Pro Leu 340 345 350
Val Lys lie Pro Gin Glu Thr lie Tyr Gly Glu Thr Val Lys Gly Pro 355 360 365
Glu Tyr Pro Thr Met Glu Asn Lys Thr Leu Gin Gly Glu lie Val Gin 370 375 380
Gly Pro Asp Phe Leu Thr Met Glu Gin Asn Arg Pro Ser Leu Sex Asp 385 390 395 400
Asn Tyr Thr Gin Pro Thr Thr Pro Asn Pro lie Leu Glu Gly Leu Glu 405 410 415
Gly Ser Ser Ser Lys Leu Glu lie Lys Pro Gin Gly Thr Glu Ser Thr 420 425 430
Leu Lys Gly lie Gin Gly Glu Ser Ser Asp lie Glu Val Lys Pro Gin 435 440 445
Ala Thr Glu Thr Thr Glu Ala Ser Gin Tyr Gly Pro Arg Fro Gin Phe 450 455 460
Asn Lys Thr Pro Lys Tyr Val Lys Tyr Arg Asp Ala Gly Thr Gly He 465 470 475 480
Arg Glu Tyr Asn Asp Gly Thr Phe Gly Tyr Glu Ala Arg Pro Arg Phe 485 490 495
Asn Lys Pro Ser Glu Thr Asn Ala Tyr Asn Val Thr Thr Asn Gin Asp 500 505 510
Gly Thr Val Ser Tyr Gly Ala Arg Pro Thr Gin Asn Lys Pro Ser Glu 515 520 525
Thr Asn Ala Tyr Asn Val Thr Thr His Ala Asn Gly Gin Val Ser Tyr 530 535 540
Gly Ala Arg Pro Thr Gin Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn 545 550 555 560
Val Thr Thr His Ala Asn Gly Gin Val Ser Tyr Gly Ala Arg Pro Thr 565 570 575
Gin Lys Lys Pro Ser Lys Thr Asn Ala Tyr Asn Val Thr Thr His Ala 580 585 590
Asn Gly Gin Val Ser Tyr Gly Ala Arg Pro Thr Tyr Lys Lys Pro Ser 595 600 605
Glu Thr Asn Ala Tyr Asn Val Thr Thr His Ala Asn Gly Gin Val Ser 610 615 620
Tyr Gly Ala Arg Pro Thr Gin Lys Lys Pro Ser Glu Thr Asn Ala Tyr 625 630 635 640
Asn Val Thr Thr His Ala Asp Gly Thr Ala Thr Tyr Gly Pro Arg Val 645 650 655 -66- 119629-序列表.doc 200815028
Thr Lys <210> 67 <211〉 961 <212> PRT <213〉葡萄球菌 <400〉 67
Met Lys Ser Asn Leu Arg Tyr Gly lie Arg Lys His Lys Leu Gly Ala 1 5 10 15
Ala Ser Val Phe Leu Gly Thr Met lie Val Val Gly Met Gly Gin Glu 20 25 30
Lys Glu Ala Ala Ala Ser Glu Gin Asn Asn Thr Thr Val Glu Glu Ser 35 40 45
Gly Ser Ser Ala Thr Glu Ser Lys Ala Ser Glu Thr Gin Thr Thr Thr 50 55 60
Asn Asn Val Asn Thr He Asp Glu Thr Gin Ser Tyr Ser Ala Thr Ser 65 70 75 80
Thr Glu Gin Pro Ser Lys Ser Thr Gin Val Thr Thr Glu Glu Ala Pro 85 90 95
Thr Thr Val Gin Ala Pro Lys Val Glu Thr Glu Met Lys Ser Gin Glu 100 105 110
Asp Leu Pro Ser Glu Lys Val Ala Asp Lys Glu Thr Thr Gly Thr Gin 115 120 125
Val Asp lie Ala Gin Pro Ser Asn Val Ser Glu lie Lys Pro Arg Met 130 135 140
Lys Arg Ser Ala Asp Val Thr Ala Val Ser Glu Lys Glu Val Ala Glu 145 150 155 160
Glu Ala Lys Ala Thr Gly Thr Asp Val Thr Asn Lys Val Glu Val Thr 165 170 175
Glu Ser Ser Leu Glu Gly His Asn Lys Asp Ser Asn lie Val Asn Pro 180 185 190
His Asn Ala Gin Arg Val Thr Leu Lys Tyr Lys Trp Lys Phe Gly Glu 195 200 205
Gly lie Lys Ala Gly Asp Tyr Phe Asp Phe Thr Leu Ser Asp Asn Val 210 215 220
Glu Thr His Gly lie Ser Thr Leu Arg Lys Val Pro Glu He Lys Ser 225 230 235 240
Ser Thr Glu Asp Lys Val Met Ala Asn Gly Gin Val He Asn Glu Arg 245 250 255
Thr lie Arg Tyr Thr Phe Thr Asp Tyr He Asn Asn Lys Lys Asp Leu 260 265 270
Thr Ala Glu Leu Asn Leu Asn Leu Phe lie Asp Pro Thr Thr Val Thr 275 280 285
Lys Gin Gly Ser Gin Lys Val Glu Val Thr Leu Gly Gin Asn Lys Val 290 295 300
Ser Lys Glu Phe Asp lie Lys Tyr Leu Asp Gly Val Lys Asp Arg Met 305 310 315 320
Gly Val 丁hr Val Asn Gly Arg lie Asp Thr Leu Asn Lys Glu Glu Gly 325 330 335
Lys Phe Ser His Phe Ala Tyr Val Lys Pro Asn Asn Gin Ser Leu Thr 340 345 350
Ser Val Thr Val Thr Gly Gin Val Thr Ser Gly Tyr Lys Gin Ser Ala 355 360 365
Asn Asn Pro Thr Val Lys Val Tyr Lys His He Gly Ser Asp Glu Leu 370 375 380
Ala Glu Ser Val Tyr Ala Lys Leu Asp Asp Thr Ser Lys Phe Glu Asp 385 390 395 400
Val Thr Glu Lys Val Asn Leu Ser Tyr Thr Ser Asn Gly Gly Tyr Thr 405 410 415
Leu Asn Leu Gly Asp Leu Asp Asn Ser Lys Asp Tyr Val lie Lys Tyr 420 425 430
Glu Gly Glu Tyr Asp Gin Asn Ala Lys Asp Leu Asn Phe Arg Thr His 435 440 445
Leu Ser Gly Tyr His Lys Tyr Tyr Pro Tyr Tyr Pro Tyr Tyr Pro Tyr 450 455 460
Tyr Pro Val Gin Leu Thr Trp Asn Asn Gly Val Ala Phe Tyr Ser Asn 465 470 475 480
Asn Ala Lys Gly Asp Gly Lys Asp Lys Pro Asn Asp Pro He lie Glu 485 490 495
Lys Ser Glu Pro lie Asp Leu Asp lie Lys Ser Glu Fro Pro Val Glu 500 505 510
Lys His Glu Leu Thr Gly Thr lie Glu Glu Ser Asn Asp Ser Lys Pro 67- 119629·序列表.doc 200815028 515 520 525 lie Asp Phe Glu Tyr His Thr Ala Val Glu Gly Ala Glu Gly His Ala 530 535 540
Glu Gly He lie Glu Thr Glu Glu Asp Ser lie His Val Asp Phe Glu 545 550 555 560
Glu Ser Thr His Glu Asn Ser Lys His His Ala Asp Val Val Glu Tyr 565 570 575
Glu Glu Asp Thr Asn Fro Gly Gly Gly Gin Val Thr Thr Glu Ser Asn 580 585 590
Leu Val Glu Phe Asp Glu Glu Ser Thr Lys Gly lie Val Thr Gly Ala 595 600 605
Val Ser Asp His Thr Thr Val Glu Asp Thr Lys Glu Tyr Thr Thr Glu 610 615 620
Ser Asn Leu lie Glu Leu Val Asp Glu Leu Pro Glu Glu His Gly Gin 625 630 635 640
Ala Gin Gly Pro lie Glu Glu lie Thr Glu Asn Asn His His lie Ser 645 650 655
His Ser Gly Leu Gly Thr Glu Asn Gly His Gly Asn Tyr Gly Val lie 660 665 670
Asp Glu lie Glu Glu Asn Ser His Val Asp lie Lys Ser Glu Leu Gly 675 680 685
Tyr Glu Gly Gly Gin Asn Ser Gly Asn Gin Ser Phe Glu Glu Asp Thr 690 695 700
Glu Glu Asp Lys Pro Lys Tyr Glu Gin Gly Gly Asn He Val Asp lie 705 710 715 720
Asp Phe Asp Ser Val Pro Gin lie His Gly Gin Asn Asn Gly Asn Gin 725 730 735
Ser Phe Glu Glu Asp Thr Glu Glu Asp Lys Pro Lys Tyr Glu Gin Gly 740 745 750
Gly Asn lie lie Asp lie Asp Phe Asp Ser Val Pro Gin lie His Gly 755 760 765
Phe Asn Lys His Asn Glu lie lie Glu Glu Asp Thr Asn Lys Asp Lys 770 775 780
Pro Asn Tyr Gin Phe Gly Gly His Asn Ser Val Asp Phe Glu Glu Asp 785 790 795 800
Thr Leu Pro Lys ¥al Ser Gly Gin Asn Glu Gly Gin Gin Thr He Glu 805 810 815
Glu Asp Thr Thr Pro Pro Thr Pro Fro Thr Pro Glu Val Pro Ser Glu 820 825 830
Fro Glu Thr Pro Thr Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Gly 835 840 845
Glu Pro Thr Pro Pro Lys Pro Glu Val Pro Ser Glu Pro Glu Thr Pro 850 855 860
Val Pro Pro Thr Pro Glu Val Pro Ser Glu Pro Gly Lys Pro Val Pro 865 870 875 880
Pro Ala Lys Glu Glu Pro Lys Lys Pro Ser Lys Pro Val Glu Gin Gly 885 890 895
Lys Val Val Thr Pro Val lie Glu lie Asn Glu Lys Val Lys Ala Val 900 905 910
Ala Pro Thr Lys Gin Lys Gin Ser Lys Lys Ser Glu Leu Pro Glu Thr 915 920 925
Gly Gly Glu Glu Ser Thr Asn Lys Gly Met Leu Phe Gly Gly Leu Phe 930 935 940
Ser lie Leu Gly Leu Val Leu Leu Arg Arg Asn Lys Lys Asn Asn Lys 945 950 955 960
Ala <210> 68 <211> 578 <212> PRT <213〉葡萄球菌 <400> 68
Met Lys Phe Lys Ser Leu lie Thr Thr Thr Leu Ala Leu Gly Val lie 1 5 10 15
Ala Ser Thr Gly Ala Asn Phe Asn Thr Asn Glu Ala Ser Ala Ala Ala 20 25 30
Lys Pro Leu Asp Lys Ser Ser Ser Thr Leu His His Gly His Ser Asn 35 40 45 lie Gin lie Pro Tyr Thr lie Thr Val Asn Gly Thr Ser Gin Asn lie 50 55 60
Leu Ser Ser Leu Thr Phe Asn Lys Asn Gin Asn lie Ser Tyr Lys Asp 65 70 75 80 68- 119629·序列表.doc 200815028 lie Glu Asn Lys Val Lys Ser Val Leu Tyr Phe Asn Arg Gly lie Ser 85 90 95
Asp lie Asp Leu Arg Leu Ser Lys Gin Ala Glu Tyr Thr Val His Phe 100 105 110
Lys Asn Gly Thr Lys Arg Val He Asp Leu Lys Ser Gly He Tyr Thr 115 120 125
Ala Asp Leu lie Asn Thr Ser Asp lie Lys Ala lie Ser Val Asn Val 130 135 140
Asp Thr Lys Lys Gin Pro Lys Asp Lys Ala Lys Ala Asn Val Gin Val 145 150 155 160
Pro Tyr Thr lie Thr Val Asn Gly Thr Ser Gin Asn lie Leu Ser-^Asn 165 170 175
Leu Thr Phe Asn Lys Asn Gin Asn lie Ser Tyr Lys Asp Leu Glu Gly 180 185 190
Lys Val Lys Ser Val Leu Glu Ser Asn Arg Gly lie Thr Asp Val Asp 195 200 205
Leu Arg Leu Ser Lys Gin Ala Lys Tyr Thr Val Asn Phe Lys Asn Gly 210 215 220
Thr Lys Lys Val lie Asp Leu Lys Ser Gly lie Tyr Thr Ala Asn Leu 225 230 235 240 lie Asn Ser Ser Asp lie Lys Ser lie Asn He Asn Val Asp Thr Lys 245 250 255
Lys His He Glu Asn Lys Ala Lys Arg Asn Tyr Gin Val Pro Tyr Ser 260 265 270 lie Asn Leu Asn Gly Thr Ser Thr Asn lie Leu Ser Asn Leu Ser Phe 275 280 285
Ser Asn Lys Pro Trp Thr Asn Tyr Lys Asn Leu Thr Ser Gin lie Lys 290 295 300
Ser Val Leu Lys His Asp Arg Gly lie Ser Glu Gin Asp Leu Lys Tyr 305 310 315 320
Ala Lys Lys Ala Tyr Tyr Thr Val Tyr Phe Lys Asn Gly Gly Lys Arg 325 330 335 lie Leu Gin Leu Asn Ser Lys Asn Tyr Thr Ala Asn Leu Val His Ala 340 345 350
Lys Asp Val Lys Arg lie Glu lie Thr Val Lys Thr Gly Thr Lys Ala 355 360 365
Lys Ala Asp Arg 丁yr Val Pro Tyr Thr lie Ala Val Asn Gly Thr Ser 370 375 380
Thr Pro He Leu Ser Lys Leu Lys lie Ser Asn Lys Gin Leu lie Ser 385 390 395 400
Tyr Lys Tyr Leu Asn Asp Lys Val Lys Ser Val Leu Lys Ser Glu Arg 405 410 415
Gly lie Ser Asp Leu Asp Leu Lys Phe Ala Lys Gin Ala Lys Tyr Thr 420 425 430
Val Tyr Phe Lys Asn Gly Lys Lys Gin Val Val Asn Leu Lys Ser Asp 435 440 445
He Phe Thr Pro Asn Leu Phe Ser Ala Lys Asp He Lys Lys He Asp 450 455 460 lie Asp Val Lys Gin Tyr Thr Lys Ser Lys Lys Lys lie Asn Lys Ser 465 470 475 480
Asn Asn Val Lys Phe Pro Val Thr lie Asn Lys Phe Glu Asn lie Val 485 490 495
Ser Asn Glu Phe Val Phe Tyr Asn Ala Ser Lys He Thr He Asn Asp 500 505 510
Leu Ser lie Lys Leu Lys Ser Ala Met Ala Asn Asp Gin Gly lie Thr 515 520 525
Lys His Asp lie Gly Leu Ala Glu Arg Ala Val Tyr Lys Val Tyr Phe 530 535 540
Lys Asn Gly Ser Ser Lys Tyr Val Asp Leu Lys Thr Glu Tyr Lys Asp 545 550 555 560
Glu Arg Val Phe Lys Ala Thr Asp lie Lys Lys Val Asp lie Glu Leu 565 570 575
Lys Phe <210〉 69 <211> 895 <212> PRT <213〉葡萄球菌 <400> 69
Met Asn Lys His His Pro Lys Leu Arg Ser Phe Tyr Ser lie Arg Lys 1 5 10 15
Ser Thr Leu Gly Val Ala Ser Val He Val Ser Thr Leu Phe Leu lie 69· 119629-序列表.doc 200815028 20 25 30
Thr Ser Gin His Gin Ala Gin Ala Ala Glu Asn Thr Asn Thr Ser Asp 35 40 45
Lys lie Ser Glu Asn Gin Asn Asn Asn Ala Thr Thr Thr Gin Pro Pro 50 55 60
Lys Asp Thr Asn Gin Thr Gin Pro Ala Thr Gin Pro Ala Asn Thr Ala 65 70 75 80
Lys Asn Tyr Pro Ala Ala Asp Glu Ser Leu Lys Asp Ala lie Lys Asp 85 90 95
Pro Ala Leu Glu Asn Lys Glu His Asp lie Gly Pro Arg Glu Gin Val 100 105 110
Asn Phe Gin Leu Leu Asp Lys Asn Asn Glu Thr Gin Tyr Tyr His Phe 115 120 125
Phe Ser lie Lys Asp Pro Ala Asp Val Tyr Tyr Thr Lys Lys Lys Ala 130 135 140
Glu Val Glu Leu Asp lie Asn Thr Ala Ser Thr Trp Lys Lys Phe Glu 145 150 155 160
Val Tyr Glu Asn Asn Gin Lys Leu Pro Yal Arg Leu Val Ser Tyr Ser 165 170 175
Pro Val Pro Glu Asp His Ala Tyr lie Arg Phe Fro Val Ser Asp Gly 180 185 190
Thr Gin Glu Leu Lys lie Val Ser Ser Thr Gin lie Asp Asp Gly Glu 195 200 205
Glu Thr Asn Tyr Asp Tyr Thr Lys Leu Val Phe Ala Lys Pro He Tyr 210 215 220
Asn Asp Pro Ser Leu Val Lys Ser Asp Thr Asn Asp Ala Val Val Thr 225 230 235 240
Asn Asp Gin Ser Ser Ser Val Ala Ser Asn Gin Thr Asn Thr Asn Thr 245 250 255
Ser Asn Gin Asn lie Ser Thr lie Asn Asn Ala Asn Asn Gin Pro Gin 260 265 270
Ala Thr Thr Asn Met Ser Gin Pro Ala Gin Pro Lys Ser Ser Thr Asn 275 280 285
Ala Asp Gin Ala Ser Ser Gin Pro Ala His Glu Thr Asn Ser Asn Gly 290 295 300
Asn Thr Asn Asp Lys Thr Asn Glu Ser Ser Asn Gin Ser Asp Vai Asn 305 310 315 320
Gin Gin Tyr Pro Pro Ala Asp Glu Ser Leu Gin Asp Ala He Lys Asn 325 330 335
Pro Ala lie lie Asp Lys Glu His Thr Ala Asp Asn Trp Arg Pro lie 340 345 350
Asp Phe Gin Met Lys Asn Asp Lys Gly Glu Arg Gin Phe Tyr His Tyr 355 360 365
Ala Ser Thr Val Glu Pro Ala Thr Val lie Phe Thr Lys Thr Gly Pro 370 375 380 lie He Glu Leu Gly Leu Lys Thr Ala Ser Thr Trp Lys Lys Phe Glu 385 390 395 400
Val Tyr Glu Gly Asp Lys Lys Leu Pro Val Glu Leu Val Ser Tyr Asp 405 410 415
Ser Asp Lys Asp Tyr Ala Tyr lie Arg Phe Pro Yal Ser Asn Gly Thr 420 425 430
Arg Glu Val Lys lie Val Ser Ser lie Glu Tyr Gly Glu Asn lie His 435 440 445
Glu Asp Tyr Asp Tyr Thr Leu Met Val Phe Ala Gin Pro lie Thr Asn 450 455 460
Asn Pro Asp Asp Tyr Yal Asp Glu Glu Thr Tyr Asn Leu Gin Lys Leu 465 470 475 480
Leu Ala Pro Tyr His Lys Ala Lys Thr Leu Glu Arg Gin Val Tyr Glu 485 490 495
Leu Glu Lys Leu Gin Glu Lys Leu Pro Glu Lys Tyr Lys Ala Glu Tyr 500 505 510
Lys Lys Lys Leu Asp Gin Thr Arg Val Glu Leu Ala Asp Gin Val Lys 515 520 525
Ser Ala Val Thr Glu Phe Glu Asn Val Thr Pro Thr Asn Asp Gin Leu 530 535 540
Thr Asp Leu Gin Glu Ala His Phe Val Val Phe Glu Ser Glu Glu Asn 545 550 555 560
Ser Glu Ser Val Met Asp Gly Phe Val Glu His Pro Phe Tyr Thr Ala 565 570 575
Thr Leu Asn Gly Gin Lys Tyr Val Val Met Lys Thr Lys Asp Asp Ser 580 585 590
Tyr Trp Lys Asp Leu He Val Glu Gly Lys Arg Val Thr Thr Val Ser 595 600 605
Lys Asp Pro Lys Asn Asn Ser Arg Thr Leu lie Phe Pro Tyr lie Pro 610 615 620 -70- 119629-序列表.doc 200815028
Asp Lys Ala Val Tyr Asn Ala lie Val Lys Val Val Val Ala Asn lie 625 630 635 640
Gly Tyr Glu Gly Gin Tyr His Val Arg He lie Asn Gin Asp lie Asn 645 650 655
Thr Lys Asp Asp Asp Thr Ser Gin Asn Asn Thr Ser Glu Pro Leu Asn 660 665 670
Val Gin Thr Gly Gin Glu Gly Lys Val Ala Asp Thr Asp Val Ala Glu 675 680 685
Asn Ser Ser Thr Ala Thr Asn Pro Lys Asp Ala Ser Asp Lys Ala Asp 690 695 700
Val He Glu Pro Glu Ser Asp Val Val Lys Asp Ala Asp Asn Asn lie 705 710 715 720
Asp Lys Asp Val Gin His Asp Val Asp His Leu Ser Asp Met Ser Asp 725 730 735
Asn Asn His Phe Asp Lys Tyr Asp Leu Lys Glu Met Asp Thr Gin He 740 745 750
Ala Lys Asp Thr Asp Arg Asn Val Asp Lys Asp Ala Asp Asn Ser Val 755 760 765
Gly Met Ser Ser Asn Val Asp Thr Asp Lys Asp Ser Asn Lys Asn Lys 770 775 780
Asp Lys Val lie Gin Leu Asn His lie Ala Asp Lys Asn Asn His Thr 785 790 795 800
Gly Lys Ala Ala Lys Leu Asp Val Val Lys Gin Asn Tyr Asn Asn Thr 805 810 815
Asp Lys Val Thr Asp Lys Lys Thr Thr Glu His Leu Pro Ser Asp lie 820 825 830
His Lys Thr Val Asp Lys Thr Val Lys Thr Lys Glu Lys Ala Gly Thr 835 840 845
Pro Ser Lys Glu Asn Lys Leu Ser Gin Ser Lys Met Leu Pro Lys Thr 850 855 860
Gly Glu Thr Thr Ser Ser Gin Ser Trp Trp Gly Leu Tyr Ala Leu Leu 865 870 875 880
Gly Met Leu Ala Leu Phe lie Pro Lys Phe Arg Lys Glu Ser Lys 885 890 895
<210> 70 <211> 747 <212> PRT <213〉葡萄球菌 <400> 70
Met Ala Glu Thr Thr Gin Asp Gin 15 Ser Asn Lys Val Lys Ala Thr Thr 20
Asn Pro Thr Gin Asn lie Ser Gly 35 40 lie Val Gin Pro Lys Thr Ala Asn 50 55
Ser Gin Lys Val Asp Thr Ala Gin 65 70
Gin Ser Ala Thr Thr Asn Asn Thr 85
Thr Thr Ala Pro Lys Thr Asn Thr 100
Leu Val Asp Asp Glu Asp Asp Asn 115 120
Leu lie Lys Ser Ala Ala Lys Pro 130 135
Thr Ala Ala Pro Lys Ala Ala Thr 145 150
Glu Ala Thr Pro Lys Val Thr Thr 165
Ser Val Ala Ala Thr Pro Lys Thr 180
Val Asn Ser Ser lie Asn Asp Tyr 195 200
Pro Lys lie Glu Glu Asp Tyr Thr 210 215
Arg Asn Gly Val Gly Arg Pro Glu 225 230
Asn Asp Arg Ser Thr lie Asn Gly 245
Tyr Gin Asn Ala Phe Val His Ala
Thr Thr Asn Lys Asn Val Leo Asp 10 15
Glu Gin Ala Lys Ala Glu Val Lys 25 30
Thr Gin Val Tyr Gin Asp Pro Ala 45
Asn Lys Thr Gly Asn Ala Gin Val 60
Val Asn Gly Asp Thr Arg Ala Asn 75 80
Gin Pro Val Ala Lys Ser Thr Ser 90 95
Asn Val Thr Asn Ala Gly Tyr Ser 105 110
Ser Glu Asn Gin He Asn Pro Glu 125
Ala Ala Leu Glu Thr Gin Tyr Lys 140
Thr Ser Ala Pro Lys Ala Lys Thr 155 160
Phe Ser Ala Ser Ala Gin Pro Arg 170 175
Ser Leu Pro Lys Tyr Lys Pro Gin 185 190
He Cys Lys Asn Asn Leu Lys Ala 205
Ser Tyr Phe Pro Lys Tyr Ala Tyr 220
Gly lie Val Val His Asp Thr Ala 235 240
Glu lie Ser Tyr Met Lys Asn Asn 250 255
Phe Val Asp Gly Asp Arg lie lie -71- 119629-序列表.doc 200815028 260 265 270
Glu Thr Ala Pro Thr Asp Tyr Leu Ser Trp Gly Val Gly Ala Val Gly 275 280 285
Asn Pro Arg Phe lie Asn Val Glu lie Val His Thr His Asp Tyr Ala 290 295 300
Ser Phe Ala Arg Ser Met Asn Asn Tyr Ala Asp Tyr Ala Ala Thr Gin 305 310 315 320
Leu Gin Tyr Tyr Gly Leu Lys Pro Asp Ser Ala Glu Tyr Asp Gly Asn 325 330 335
Gly Thr Val Trp Thr His Tyr Ala Val Ser Lys Tyr Leu Gly Gly Thr 340 345 350
Asp His Ala Asp Pro His Gly Tyr Leu Arg Ser His Asn Tyr Ser Tyr 355 360 365
Asp Gin Leu Tyr Asp Leu lie Asn Glu Lys Tyr Leu lie Lys Met Gly 370 375 380
Lys Val Ala Pro Trp Gly Thr Gin Ser Thr Thr Thr Pro Thr Thr Pro 385 390 395 400
Ser Lys Pro Thr Thr Pro Ser Lys Pro Ser Thr Gly Lys Leu Thr Val 405 410 415
Ala Ala Asn Asn Gly Val Ala Gin lie Lys Pro Thr Asn Ser Gly Leu 420 425 430
Tyr Thr Thr Val Tyr Asp Lys Thr Gly Lys Ala Thr Asn Glu Val Gin 435 440 445
Lys Thr Phe Ala Val Ser Lys Thr Ala Thr Leu Gly Asn Gin Lys Phe 450 455 460
Tyr Leu Val Gin Asp Tyr Asn Ser Gly Asn Lys Phe Gly Trp Val Lys 465 470 475 480
Glu Gly Asp Val Val Tyr Asn Thr Ala Lys Ser Pro Val Asn Val Asn 485 490 495
Gin Ser Tyr Ser lie Lys Pro Gly Thr Lys Leu Tyr Thr Val Pro Trp 500 505 510
Gly Thr Ser Lys Gin Val Ala Gly Ser Val Ser Gly Ser Gly Asn Gin 515 520 525
Thr Phe Lys Ala Ser Lys Gin Gin Gin lie Asp Lys Ser He Tyr Leu 530 535 540
Tyr Gly Ser Val Asn Gly Lys Ser Gly Trp Val Ser Lys Ala Tyr Leu 545 550 555 560
Val Asp Thr Ala Lys Pro Thr Pro Thr Pro Thr Pro Lys Pro Ser Thr 565 570 575
Pro Thr Thr Asn Asn Lys Leu Thr Val Ser Ser Leu Asn Gly Val Ala 580 585 590
Gin lie Asn Ala Lys Asn Asn Gly Leu Phe Thr Thr Val Tyr Asp Lys 595 600 605
Thr Gly Lys Pro Thr Lys Glu Val Gin Lys Thr Phe Ala Val Thr Lys 610 615 620
Glu Ala Ser Leu Gly Gly Asn Lys Phe Tyr Leu Val Lys Asp lyr Asn 625 630 635 640
Ser Pro Thr Leu lie Gly Trp Val Lys Gin Gly Asp Val lie Tyr Asn 645 650 655
Asn Ala Lys Ser Pro Val Asn Val Met Gin Thr Tyr Thr Val Lys Pro 660 665 670
Gly Thr Lys Leu Tyr Ser Val Pro Trp Gly Thr Tyr Lys Gin Glu Ala 675 680 685
Gly Ala Val Ser Gly Thr Gly Asn Gin Thr Phe Lys Ala Thr Lys Gin 690 695 700
Gin Gin He Asp Lys Ser lie Tyr Leu Phe Gly Thr Val Asn Giy Lys 705 710 715 720
Ser Gly Trp Val Ser Lys Ala Tyr Leu Ala Val Pro Ala Ala Pro Lys 725 730 735
Lys Ala Val Ala Gin Pro Lys Thr Aia Val Lys 740 745 <210> 71 <211> 482 <212> PRT <213〉葡萄球菌 <400> 71
Met Ala Tyr Thr Val Thr Lys Fro Gin Thr Thr Gin Thr Val Ser Lys 15 10 15 lie Ala Gin Val Lys Pro Asn Asn Thr Gly lie Arg Ala Ser Val Tyr 20 25 30
Glu Lys Thr Ala Lys Asn Gly Ala Lys Tyr Ala Asp Arg Thr Phe Tyr 35 40 45 72- 119629-序列表.doc 200815028
Val Thr Lys GIu Arg Ala His Gly Asn Glu Thr Tyr Val Leu Leu Asn 50 55 60
Asn Thr Ser His Asn lie Pro Leu Gly Trp Phe Asn Val Lys Asp Leu 65 70 75 80
Asn Val Gin Asn Leu Gly Lys Glu Val Lys Thr Thr Gin Lys Tyr Thr 85 90 95
Val Asn Lys Ser Asn Asn Gly Leu Ser Met Val Pro Trp Gly Thr Lys 100 105 110
Asn Gin Val He Leu Thr Gly Asn Asn lie Ala Gin Gly Thr Phe Asn 115 120 125
Ala Thr Lys Gin Val Ser Val Gly Lys Asp Val Tyr Leu Tyr Gly Thr 130 135 140 lie Asn Asn Arg Thr Gly Trp Val Asn Ala Lys Asp Leu Thr Ala Pro 145 150 155 160
Thr Ala Val Lys Pro Thr Thr Ser Ala Ala Lys Asp lyr Asn Tyr Thr 165 170 175
Tyr Val He Lys Asn Gly Asn Gly Tyr Tyr Tyr Val Thr Fro Asn Ser 180 185 190
Asp Thr Ala Lys Tyr Ser Leu Lys Ala Phe Asn Glu Gin Pro Phe Ala 195 200 205
Val Val Lys Glu Gin Val lie Asn Gly Gin Thr Trp Tyr Tyr Gly Lys 210 215 220
Leu Ser Asn Gly Lys Leu Ala Trp lie Lys Ser Thr Asp Leu Ala Lys 225 230 235 240
Glu Leu lie Lys Tyr Asn Gin Thr Giy Met Thr Leu Asn Gin Val Ala 245 250 255
Gin lie Gin Ala Gly Leu Gin Tyr Lys Pro Gin Val Gin Arg Val Pro 260 265 270
Gly Lys Trp Thr Asp Ala Lys Phe Asn Asp Val Lys His Ala Met Asp 275 280 285
Thr Lys Arg Leu Ala Gin Asp Pro Ala Leu Lys Tyr Gin Phe Leu Arg 290 295 300
Leu Asp Gin Pro Gin Asn lie Ser lie Asp Lys lie Asn Gin Phe Leu 305 310 315 220
Lys Gly Lys Gly Val Leu Glu Asn Gin Gly Ala Ala Phe Asn Lys Ala 325 330 335
Ala Gin Met Tyr Gly lie Asn Glu Val Tyr Leu lie Ser His Ala Leu 340 345 350
Leu Glu Thr Gly Asn Gly Thr Ser Gin Leu Ala Lys Gly Ala Asp Val 355 360 365
Val Asn Asn Lys Val Val Thr Asn Ser Asn Thr Lys Tyr His Asn Val 370 375 380
Phe Gly He Ala Ala Tyr Asp Asn Asp Pro Leu Arg Glu Gly lie Lys 385 390 395 400
Tyr Ala Lys Gin Ala Gly Trp Asp Thr Val Ser Lys Ala lie Val Gly 405 410 415
Gly Ala Lys Phe lie Gly Asn Ser Tyr Val Lys Ala Gly Gin Asn Thr 420 425 430
Leu Tyr Lys Met Arg Trp Asn Pro Ala His Pro Gly Thr His Gin Tyr 435 440 445
Ala Thr Asp Val Asp Trp Ala Asn lie Asn Ala Lys He lie Lys Gly 450 455 460
Tyr Tyr Asp Lys lie Gly Glu Val Gly Lys Tyr Phe Asp He Pro Gin 465 470 475 480
Tyr Lys <210〉 72 <211> 706 <212> PRT <213〉葡萄球菌 <400〉 72
Asp Arg Val Leu Ala Ser His Pro Asp Val Ala Thr lie Arg Gin Asn 1 5 10 15
Val Thr Ala Ala Asn Ala Ala Lys Ser Ala Leu Asp Gin Ala Arg Asn 20 25 30
Gly Leu Thr Val Asp Lys Ala Pro Leu Glu Asn Ala Lys Asn Gin Leu 35 40 45
Gin His Ser lie Asp Thr Gin Thr Ser Thr Thr Gly Met Thr Gin Asp 50 55 60
Ser lie Asn Ala Tyr Asn Ala Lys Leu Thr Ala Ala Arg Asn Lys He 65 70 75 80
Gin Gin lie Asn Gin Val Leu Ala Gly Ser Pro Thr Val Glu Gin lie 73- 119629-序列表.doc 200815028 85 90 95
Asn Thr Asn Thr Ser Thr Ala Asn Gin Ala Lys Ser Asp Leu Asp His 100 105 110
Ala Arg Gin Ala Leu Thr Pro Asp Lys Ala Pro Leu.Gin Thr Ala Lys 115 120 125
Thr Gin Leu Glu Gin Ser lie Asn Gin Pro Thr Asp Thr Thr Giy Met 130 135 140
Thr Thr Ala Ser Leu Asn Ala Tyr Asn Gin Lys Leu Gin Ala Ala Arg 145 150 155 160
Gin Lys Leu Thr Glu lie Asn Gin Val Leu Asn Gly Asn Pro Thr ¥al 165 170 175
Gin Asn lie Asn Asp Lys Val Thr Glu Ala Asn Gin Ala Lys Asp Gin 180 185 190
Leu Asn Thr Ala Arg Gin Gly Leu Thr Leu Asp Arg Gin Pro Ala Leu 195 200 205
Thr Thr Leu His Gly Ala Ser Asn Leu Asn Gin Ala Gin Gin Asn Asn 210 215 220
Phe Thr Gin Gin lie Asn Ala Ala Gin Asn His Ala Ala Leu Glu Thr 225 230 235 240 lie Lys Ser Asn lie Thr Ala Leu Asn Thr Ala Met Thr Lys Leu Lys 245 250 255
Asp Ser Val Ala Asp Asn Asn Thr lie Lys Ser Asp Gin Asn Tyr Thr 260 265 270
Asp Ala Thr Pro Ala Asn Lys Gin Ala Tyr Asp Asn Ala Val Asn Ala 275 280 285
Ala Lys Gly Val He Gly Glu Thr Thr Asn Pro Thr Met Asp Val Asn 290 295 300
Thr Val Asn Gin Lys Ala Ala Ser Val Lys Ser Thr Lys Asp Ala Leu 305 310 315 320
Asp Gly Gin Gin Asn Leu Gin Arg Ala Lys Thr Glu Ala Thr Asn Ala 325 330 335 lie Thr His Ala Ser Asp Leu Asn Gin Ala Gin Lys Asn Ala Leu Thr 340 345 350
Gin Gin Val Asn Ser Ala Gin Asn Val Gin Ala Val Asn Asp lie Lys 355 360 365
Gin Thr Thr Gin Ser Leu Asn Thr Ala Met Thr Gly Leu Lys Arg Gly 370 375 380
Val Ala Asn His Asn Gin Val Val Gin Ser Asp Asn Tyr Val Asn Ala 385 390 395 400
Asp Thr Asn Lys Lys Asn Asp Tyr Asn Asn Ala Tyr Asn His Ala Asn 405 410 415
Asp lie lie Asn Gly Asn Ala Gin His Pro Val lie Thr Pro Ser Asp 420 425 430
Val Asn Asn Ala Leu Ser Asn Val Thr Ser Lys Glu His Ala Leu Asn 435 440 445
Gly Glu Ala Lys Leu Asn Ala Ala Lys Gin Glu Ala Asn Thr Ala Leu 450 455 460
Gly His Leu Asn Asn Leu Asn Asn Ala Gin Arg Gin Asn Leu Gin Ser 465 470 475 480
Gin lie Asn Gly Ala His Gin He Asp Ala Val Asn Thr He Lys Gin 485 490 495
Asn Ala Thr Asn Leu Asn Ser Ala Met Gly Asn Leu Arg Gin Ala Val 500 505 510
Ala Asp Lys Asp Gin Val Lys Arg Thr Glu Asp Tyr Ala Asp Ala Asp 515 520 525
Thr Ala Lys Gin Asn Ala Tyr Asn Ser Ala Val Ser Ser Ala Giu Thr 530 535 540 lie lie Asn Gin Thr Thr Asn Pro Thr Met Ser Val Asp Asp Val Asn 545 550 555 560
Arg Ala Thr Ser Ala Val Thr Ser Asn Lys Asn Ala Leu Asn Gly Tyr 565 570 575
Glu Lys Leu Ala Gin Ser Lys Thr Asp Ala Ala Arg Ala lie Asp Ala 580 585 590
Leu Pro His Leu Asn Asn Ala Gin Lys Ala Asp Val Lys Ser Lys He 595 600 605
Asn Ala Ala Ser Asn He Ala Gly Val Asn Thr Val Lys Gin Gin Gly 610 615 620
Thr Asp Leu Asn Thr Ala Met Gly Asn Leu Gin Gly Ala He Asn Asp 625 630 635 640
Glu Gin Thr Thr Leu Asn Ser Gin Asn Tyr Gin Asp Ala Thr Pro Ser 645 650 655
Lys Lys Thr Ala Tyr Thr Asn Ala Val Gin Ala Ala Lys Asp lie Leu 660 665 670
Asn Lys Ser Asn Gly Gin Asn Lys Thr Lys Asp Gin Val Thr Glu Ala 675 680 685 74- 119629-序列表.doc 200815028
Met Asn Gin Val Asn Ser Ala Lys Asn Asn Leu Asp Gly Thr Arg Leu 690 695 700
Leu Asp 705 <210〉 73 <21I> 241 <212> PRT 〈213〉葡麵菌 <400> 73
Ala Ser Thr Gin His Thr Val Gin Ser Gly Glu Ser Leu Trp Ser He 1 5 10 15
Ala Gin Lys Tyr Asn Thr Ser Val Glu Ser lie Lys Gin Asn Asn Gin 20 25 30
Leu Asp Asn Asn Leu Val Phe Pro Gly Gin Val lie Ser Val Gly Gly 35 40 45
Ser Asp Ala Gin Asn Thr Ser Asn Thr Ser Pro Gin Ala Gly Ser Ala 50 55 60
Ser Ser His了hr Val Gin Ala Gly Glu Ser Leu Asn lie lie Ala Ser 65 70 75 80
Arg Tyr Gly Val Ser Val Asp Gin Leu Met Ala Ala Asn Asn Leu Arg 85 90 95
Gly Tyr Leu He Met Pro Asn Gin Thr Leu Gin lie Pro Asn Gly Gly 100 105 110
Ser Gly Gly Thr Thr Pro Thr Ala Thr Thr Gly Ser' Asn Gly Asn Ala 115 120 125
Ser Ser Phe Asn His Gin Asn Leu Tyr Thr Ala Gly Gin Cys Thr Trp 130 135 140
Tyr Val Phe Asp Arg Arg Ala Gin Ala Gly Ser Pro lie Ser Thr Tyr 145 150 155 160
Trp Ser Asp Ala Lys Tyr Trp Ala Gly Asn Ala Ala Asn Asp Gly Tyr 165 170 175
Gin Val Asn Asn Thr Pro Ser Val Gly Ser lie Met Gin Ser Thr Pro 180 185 190
Gly Pro Tyr Gly His Val Ala Tyr Val Glu Arg Val Asn Gly Asp Gly 195 200 205
Ser He Leu lie Ser Glu Met Asn Tyr Thr Tyr Gly Pro Tyr Asn Met 210 215 220
Asn Tyr Arg Thr lie Pro Ala Ser Glu Val Ser Ser Tyr Ala Phe lie 225 230 235 240
His <210〉 74 <211> 995 <212> PRT <213〉葡萄球菌 <400> 74
Asn Arg Lys Gly Met lie Pro Asn 10 15 Lys Tyr Ser Val Gly Thr Ala Ser 25 30 Phe Gly Leu Ser Gly His Glu Ala 45 Glu Leu Asn Gin Ser Lys Asn Glu 60 Thr Thr Lys Lys Val Asp Ser Arg 75 80 Ala Thr Ala Asp Gin Fro Lys Val 90 95 Lys Glu Thr Ser Ser Asn Met Gin 105 110 Gin Ser Thr Thr Lys Thr Ser Asn 125 Thr Thr Tyr Ser Asn Glu Thr Asp 140 Asp Val Ser Thr Thr Pro Lys Thr 155 160 Asn Arg Met Ala Val Asn Thr Val 170 175 Val Asn Asp Lys Val His Phe Ser
Met Asn Asn Lys Lys Thr Ala Thr I 5
Arg Leu Asn Lys Phe Ser lie Arg 20 lie Leu Val Gly Thr Thr Leu lie 35 40
Lys Ala Ala Glu His Thr Asn Gly 50 55
Thr Thr Ala Pro Ser Glu Asn Lys 65 70
Gin Leu Lys Asp Asn Thr Gin Thr 85
Thr Uet Ser Asp Ser Ala Thr Val 100
Ser Pro Gin Asn Ala Thr Ala Asn 115 120
Val Thr Thr Asn Asp Lys Ser Ser 130 135
Lys Ser Asn Leu Thr Gin Ala Lys 145 150
Thr Thr lie Lys Pro Arg Thr Leu 165
Ala Ala Pro Gin Gin Gly Thr Asn 75- 119629-序列表.doc 200815028 180 185 190
Asn He Asp lie Ala lie Asp Lys Gly His Val Asn Gin Thr Thr Gly 195 200 205
Lys Thr Glu Phe Trp Ala Thr Ser Ser Asp Val Leu Lys Leu Lys Ala 210 215 220
Asn Tyr Thr lie Asp Asp Ser Val Lys Glu Gly Asp Thr Phe Thr Fhe 225 230 235 240
Lys Tyr Gly Gin Tyr Phe Arg Pro Gly Ser Val Arg Leu Pro Ser Gin 245 250 255
Thr Gin Asn Leu Tyr Asn Ala Gin Gly Asn He lie Ala Lys Gly lie 260 265 270
Tyr Asp Ser Thr Thr Asn Thr Thr Thr Tyr Thr Phe Thr Asn Tyr Val 275 280 285
Asp Gin Tyr Thr Asn Val Arg Gly Ser Phe Glu Gin Val Ala Phe Ala 290 295 300
Lys Arg Lys Asn Ala Thr Thr Asp Lys Thr Ala Tyr Lys Met Glu Val 305 310 315 320
Thr Leu Gly Asn Asp Thr Tyr Ser Glu Glu lie lie Val Asp Tyr Gly 325 330 335
Asn Lys Lys Ala Gin Fro Leu lie Ser Ser Thr Asn Tyr He Asn Asn 340 345 350
Glu Asp Leu Ser Arg Asn Met Thr Ala Tyr Val Asn Gin Pro Lys Asn 355 360 365
Thr Tyr Thr Lys Gin Thr Phe Val Thr Asn Leu Thr Gly Tyr Lys Fhe 370 375 380
Asn Pro Asn Ala Lys Asn Phe Lys lie Tyr Glu Val Thr Asp Gin Asn
385 390 395 400
Gin Phe Val Asp Ser Phe Thr Pro Asp Thr Ser Lys Leu Lys Asp Val 405 410 415
Thr Asp Gin Fhe Asp Val lie Tyr Ser Asn Asp Asn Lys Thr Ala Thr 420 425 430
Val Asp Leu Met Lys Gly Gin Thr Ser Ser Asn Lys Gin Tyr lie lie 435 440 445
Gin Gin Val Ala Tyr Pro Asp Asn Ser Ser Thr Asp Asn Gly Lys lie 450 455 460
Asp Tyr Thr Leu Asp Thr Asp Lys Thr Lys Tyr Ser Trp Ser Asn Ser 465 470 475 480
Tyr Ser Asn Val Asn Gly Ser Ser Thr Ala Asn Gly Asp Gin Lys Lys 485 490 495
Tyr Asn Leu Gly Asp Tyr Val Trp Glu Asp Thr Asn Lys Asp Gly Lys 500 505 510
Gin Asp Ala Asn Glu Lys Gly lie Lys Gly Val Tyr Val lie Leu Lys 515 520 525
Asp Ser Asn Gly Lys Glu Leu Asp Arg Thr Thr Thr Asp Glu Asn Gly 530 535 540
Lys Tyr Gin Phe Thr Gly Leu Ser Asn Gly Thr Tyr Ser Val Glu Phe 545 550 555 560
Ser Thr Pro Ala Gly Tyr Thr Pro Thr Thr Ala Asn Val Gly Thr Asp 565 570 575
Asp Ala Val Asp Ser Asp Gly Leu Thr Thr Thr Gly Val lie Lys Asp 580 585 590
Ala Asp Asn Met Thr Leu Asp Ser Gly Phe Tyr Lys Thr Pro Lys Tyr 595 600 605
Ser Leu Gly Asp Tyr Val Trp Tyr Asp Ser Asn Lys Asp Gly Lys Gin 610 615 620
Asp Ser Thr Glu Lys Gly lie Lys Gly Val Lys Val Thr Leu Gin Asn 625 630 635 640
Glu Lys Gly Glu Val lie Gly Thr Thr Glu Thr Asp Glu Asn Gly Lys 645 650 655
Tyr Arg Phe Asp Asn Leu Asp Ser Gly Lys Tyr Lys Val lie Phe Glu 660 665 670
Lys Pro Ala Gly Leu Thr Gin Thr Gly Thr Asn Thr Thr Glu Asp Asp 675 680 685
Lys Asp Ala Asp Gly Gly Glu Val Asp Val Thr He Thr Asp His Asp 690 695 700
Asp Phe Thr Leu Asp Asn Gly Tyr Tyr Glu Glu Glu Thr Ser Asp Ser 705 710 715 720
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 725 730 735
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 740 745 750
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 755 760 765
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 770 775 780 -76- 119629-序列表.doc 200815028
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 785 790 795 800
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 805 810 815
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 820 825 830
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 835 840 845
Asp Ser Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Ser Asp Ser 850 855 860
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 865 870 875 880
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 885 890 895
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser 900 905 910
Asp Ser Asp Ser Asp Ser Asp Ser Asp Ser Asp Asn Asp Ser Asp Ser 915 920 925
Asp Ser Asp Ser Asp Ser Asp Ala Gly Lys His Thr Pro Ala Lys Pro 930 935 940
Met Ser Thr Val Lys Asp Gin His Lys Thr Ala Lys Ala Leu Pro Glu 945 950 955 960
Thr Gly Ser Glu Asn Asn Asn Ser Asn Asn Gly Thr Leu Phe Gly Gly 965 970 975
Leu Phe Ala Ala Leu Gly Ser Leu Leu Leu Phe Gly Arg Arg Lys Lys 980 985 990
Gin Asn Lys 995 <210〉 75 <211〉 2186 <212〉 PRT <213〉葡萄球菌 <400> 75
Met Asn Leu Leu Lys Lys Asn Lys Tyr Ser He Arg Lys Tyr Lys Val 1 5 10 15
Gly He Phe Ser Thr Leu lie Gly Thr Val Leu Leu Leu Ser Asn Pro 20 25 30
Asn Gly Ala Gin Ala Leu Thr Thr Asp Asn Asn Val Gin Ser Asp Thr 35 40 45
Asn Gin Ala Thr Pro Val Asn Ser Gin Asp Lys Asp Val Ala Asn Asn 50 55 60
Arg Gly Leu Ala Asn Ser Ala Gin Asn Thr Pro Asn Gin Ser Ala Thr 65 70 75 80
Thr Asn Gin Ala Thr Asn Gin Ala Leu Val Asn His Asn Asn Gly Ser 85 90 95 lie Val Asn Gin Ala Thr Pro Thr Ser Val Gin Ser Ser Thr Pro Ser 100 105 110
Ala Gin Asn Asn Asn His Thr Asp Gly Asn Thr Thr Ala Thr Glu Thr 115 120 125
Val Ser Asn Ala Asn Asn Asn Asp Val Val Ser Asn Asn Thr Ala Leu 130 135 140
Asn Val Pro Thr Lys Thr Asn Glu Asn Gly Ser Gly Gly His Leu Thr 145 150 155 160
Leu Lys Glu lie Gin Glu Asp Val Arg His Ser Ser Asn Lys Pro Glu 165 170 175
Leu Val Ala He Ala Glu Pro Ala Ser Asn Arg Pro Lys Lys Arg Ser 180 185 190
Arg Arg Ala Ala Pro Ala Asp Pro Asn Ala Thr Pro Ala Asp Pro Ala 195 200 205
Ala Ala Ala Val Gly Asn Gly Gly Ala Pro Val Ala lie Thr Ala Pro 210 215 220
Tyr Thr Pro Thr Thr Asp Pro Asn Ala Asn Asn Ala Gly Gin Asn Ala 225 230 235 240
Pro Asn Glu Val Leu Ser Phe Asp Asp Asn Gly lie Arg Pro Ser Thr 245 250 255
Asn Arg Ser Val Pro Thr Val Asn Val Val Asn Asn Leu Pro Gly Phe 260 265 270
Thr Leu lie Asn Gly Gly Lys Val Gly Val Phe Ser His Ala Met Val 275 280 285
Arg Thr Ser Met Phe Asp Ser Gly Asp Asn Lys Asn Tyr Gin Ala Gin 290 295 300
Gly Asn Val He Ala Leu Gly Arg lie His Gly Thr Asp Thr Asn Asp 77- 119629-序列表.doc 200815028 305 310 315 320
His Gly Asp Phe Asn Gly lie Glu Lys Ala Leu Thr Val Asn Pro Asn 325 330 335
Ser Glu Leu He Phe Glu Phe Asn Thr Met Thr Thr Lys Asn Gly Gin 340 345 350
Gly Ala Thr Asn Val He He Lys Asn Ala Asp Thr Asn Asp Thr lie 355 360 365
Ala Glu Lys Thr Val Glu Gly Gly Pro Thr Leu Arg Leu Phe Lys Val 370 375 380
Pro Asp Asn Val Arg Asn Leu Lys lie Gin Phe Val Pro Lys Asn Asp 385 390 395 400
Ala He Thr Asp Ala Arg Gly He Tyr Gin Leu Lys Asp Gly Tyr Lys 405 410 415
Tyr Tyr Ser Fhe Val Asp Ser lie Gly Leu His Ser Gly Ser His Val 420 425 430
Phe Val Glu Arg Arg Thr Met Asp Pro Thr Ala Thr Asn Asn Lys Giu 435 440 445
Phe Thr Val Thr Thr Ser Leu Lys Asn Asn Gly Asn Ser Gly Ala Ser 450 455 460
Leu Asp Thr Asn Asp Phe Val Tyr Gin Val Gin Leu Pro Glu Gly Val 465 470 475 480
Glu Tyr ¥al Asn Asn Ser Leu Thr Lys Asp Phe Pro Ser Asn Asn Ser 485 490 495
Gly Val Asp Val Asn Asp Met Asn Val Thr Tyr Asp Ala Ala Asn Arg 500 505 510
Val lie Thr He Lys Ser Thr Gly Gly Gly Thr Ala Asn Ser Pro Ala 515 520 525
Arg Leu Met Pro Asp Lys lie Leu Asp Leu Arg Tyr Lys Leu Arg Val 530 535 540
Asn Asn Val Pro Thr Pro Arg Thr Val Thr Phe Asn Glu Thr Leu Thr 545 550 555 560
Tyr Lys Thr Tyr Thr Gin Asp Phe lie Asn Ser Ala Ala Glu Ser His 565 570 575
Thr Val Ser Thr Asn Pro Tyr Thr lie Asp lie lie Met Asn Lys Asp 580 585 590
Ala Leu Gin Ala Glu Val Asp Arg Arg lie Gin Gin Ala Asp Tyr Thr 595 600 605
Phe Ala Ser Leu Asp lie Phe Asn Gly Leu Lys Arg Arg Ala Gin Thr 610 615 620 lie Leu Asp Glu Asn Arg Asn Asn Val Pro Leu Asn Lys Arg Val Ser 625 630 635 640
Gin Ala Tyr lie Asp Ser Leu Thr Asn Gin Met Gin His Thr Leu lie 645 650 655
Arg Ser Val Asp Ala Glu Asn Ala Val Asn Lys Lys Val Asp Gin Met 660 665 670
Glu Asp Leu Val Asn Gin Asn Asp Glu Leu Thr Asp Glu Glu Lys Gin 675 680 685
Ala Ala lie Gin Val He Glu Glu His Lys Asn Glu lie lie Gly Asn 690 695 700 lie Gly Asp Gin Thr Thr Asp Asp Gly Val Thr Arg lie Lys Asp Gin 705 710 715 720
Gly lie Gin Thr Leu Ser Gly Asp Thr Ala Thr Pro Val Val Lys Pro 725 730 735
Asn Ala Lys Lys Ala lie Arg Asp Lys Ala Thr Lys Gin Arg Glu lie 740 745 750
He Asn Ala Thr Pro Asp Ala Thr Glu Asp Glu He Gin Asp Ala Leu 755 760 765
Asn Gin Leu Ala Thr Asp Glu Thr Asp Ala lie Asp Asn Val Thr Asn 770 775 780
Ala Thr Thr Asn Ala Asp Val Glu Thr Ala Lys Asn Asn Gly lie Asn 785 790 795 800
Thr lie Gly Ala Val Val Pro Gin Val Thr His Lys Lys Ala Ala Arg 805 810 815
Asp Ala lie Asn Gin Ala Thr Ala Thr Lys Arg Gin Gin lie Asn Ser 820 825 830
Asn Arg Glu Ala Thr Gin Glu Glu Lys Asn Ala Ala Leu Asn Glu Leu 835 840 845
Thr Gin Ala Thr Asn His Ala Leu Glu Gin lie Asn Gin Ala Thr Thr 850 855 860
Asn Ala Asn Val Asp Asn Ala Lys Gly Asp Gly Leu Asn Ala lie Asn 865 870 875 B80
Pro lie Ala Pro Val Thr Val Val Lys Gin Ala Ala Arg Asp Ala Val 885 890 895 -78- 119629·序列表.doc 200815028
Ser His Asp Ala Gin Gin His He Ala Glu lie Asn Ala Asn Pro Asp 900 905 910
Ala Thr Gin Glu Glu Arg Gin Ala Ala lie Asp Lys Val Asn Ala Ala 915 920 925
Val Thr Ala Ala Asn Thr Asn lie Leu Asn Ala Asn Thr Asn Ala Asp 930 935 940
Val Glu Gin Val Lys Thr Asn Ala lie Gin Gly He Gin Ala lie Thr 945 950 955 960
Pro Ala Thr Lys Val Lys Thr Asp Ala Lys Asn Ala lie Asp Lys Ser 965 970 975
Ala Glu Thr Gin His Asn Thr He Phe Asn Asn Asn Asp Ala Thr Leu 980 985 990
Glu Glu Gin Gin Ala Ala Gin Gin Leu Leu Asp Gin Ala Val Ala Thr 995 1000 1005
Ala Lys Gin Asn lie Asn Ala Ala Asp Thr Asn Gin Glu Val Ala Gin 1010 1015 1020
Ala Lys Asp Gin Gly Thr Gin Asn lie Val Val He Gin Fro Ala Thr 1025 1030 1035 1040
Gin Val Lys Thr Asp Thr Arg Asn Val Val Asn Asp Lys Ala Arg Glu 1045 1050 1055
Ala lie Thr Asn He Asn Ala Thr Thr Gly Ala Thr Arg Glu Glu Lys 1060 1065 1070
Gin Glu Ala lie Asn Arg Val Asn Thr Leu Lys Asn Arg Ala Leu Thr 1075 1080 1085
Asp lie Gly Val Thr Ser Thr Thr Ala Met Val Asn Ser lie Arg Asp 1090 1095 1100
Asp Ala Val Asn Gin lie Gly Ala Val Gin Pro His Val Thr Lys Lys 1105 1110 1115 1120
Gin Thr Ala Thr Gly Val Leu Asn Asp Leu Ala Thr Ala Lys Lys Gin 1125 1130 1135
Glu lie Asn Gin Asn Thr Asn Ala Thr Thr Glu Glu Lys Gin Val Ala 1140 1145 1150
Leu Asn Gin Val Asp Gin Glu Leu Ala Thr Ala lie Asn Asn He Asn 1155 1160 1165
Gin Ala Asp Thr Asn Ala Glu Val Asp Gin Ala Gin Gin Leu Gly Thr 1170 1175 1180
Lys Ala lie Asn Ala lie Gin Pro Asn He Val Lys Lys Pro Ala Ala 1185 1190 1195 1200
Leu Ala Gin lie Asn Gin His Tyr Asn Ala Lys Leu Ala Glu He Asn 1205 1210 1215
Ala Thr Pro Asp Ala Thr Asn Asp Glu Lys Asn Ala Ala lie Asn Thr 1220 1225 1230
Leu Asn Gin Asp Arg Gin Gin Ala lie Glu Ser lie Lys Gin Ala Asn 1235 1240 1245
Thr Asn Ala Glu Val Asp Gin Ala Ala Thr Val Ala Glu Asn Asn lie 1250 1255 1260
Asp Ala Val Gin Val Asp Val Val Lys Lys Gin Ala Ala Arg Asp Lys 1265 1270 1275 1280 lie Thr Ala Glu Val Ala Lys Arg lie Glu Ala Val Lys Gin Thr Pro 1285 1290 1295
Asn Ala Thr Asp Glu Glu Lys Gin Ala Ala Val Asn Gin lie Asn Gin 1300 1305 1310
Leu Lys Asp Gin Ala lie Asn Gin He Asn Gin Asn Gin Thr Asn Asp 1315 1320 1325
Gin Val Asp Thr Thr Thr Asn Gin Ala Val Asn Ala lie Asp Asn Val 1330 1335 1340
Glu Ala Glu Val Val lie Lys Thr Lys Ala lie Ala Asp He Glu Lys 1345 1350 1355 1360
Ala Val Lys Glu Lys Gin Gin Gin lie Asp Asn Ser Leu Asp Ser Thr 1365 1370 1375
Asp Asn Glu Lys Glu Val Ala Ser Gin Ala Leu Ala Lys Glu Lys Glu 1380 1385 1390
Lys Ala Leu Ala Ala lie Asp Gin Ala Gin Thr Asn Ser Gin Val Asn 1395 1400 1405
Gin Ala Ala Thr Asn Gly Val Ser Ala He Lys lie lie Gin Pro Glu 1410 1415 1420
Thr Lys Val Lys Pro Ala Ala Arg Glu Lys lie Asn Gin Lys Ala Asn 1425 1430 1435 1440
Glu Leu Arg Ala Lys He Asn Gin Asp Lys Glu Ala Thr Ala Glu Glu 1445 1450 1455
Arg Gin Val Ala Leu Asp Lys lie Asn Glu Phe Val Asn Gin Ala Met 1460 1465 1470
Thr Asp lie Thr Asn Asn Arg Thr Asn Gin Gin Val Asp Asp Thr Thr 1475 1480 1485
Ser Gin Ala Leu Asp Ser lie Ala Leu Val Thr Pro Asp His lie Val 79- 119629-序列表.doc 200815028 1490 1495 1500
Arg Ala Ala Ala Arg Asp Ala Val Lys Gin Gin Tyr Glu Ala Lys Lys 1505 1510 1515 1520
Arg Glu He Glu Gin Ala Glu His Ala Thr Asp Glu Glu Lys Gin Val 1525 1530 1535
Ala Leu Asn Gin Leu Ala Asn Asn Glu Lys Arg Ala Leu Gin Asn He 1540 1545 1550
Asp Gin Ala lie Ala Asn Asn Asp Val Lys Arg Val Glu Thr Asn Gly 1555 1560 1565
He Ala Thr Leu Lys Gly Val Gin Pro His lie Val He Lys Pro Glu 1570 1575 1580
Ala Gin Gin Ala lie Lys Ala Ser Ala Glu Asn Gin Val Glu Ser He 1585 1590 1595 1600
Lys Asp Thr Pro His Ala Thr Val Asp Glu Leu Asp Glu Ala Asn Gin 1605 1610 1615
Leu lie Ser Asp Thr Leu Lys Gin Ala Gin Gin Glu lie Glu Asn Thr 1620 1625 1630
Asn Gin Asp Ala Ala Val Thr Asp Val Arg Asn Gin Thr lie Lys Ala 1635 1640 1645
He Glu Gin lie Lys Pro Lys Val Arg Arg Lys Arg Ala Ala Leu Asp 1650 1655 1660
Ser lie Glu Glu Asn Asn Lys Asn Gin Leu Asp Ala He Arg Asn Thr 1665 1670 1675 1680
Leu Asp Thr Thr Gin Asp Glu Arg Asp Val Ala lie Asp Thr Leu Asn 1685 1690 1695
Lys lie Val Asn Thr lie Lys Asn Asp lie Ala Gin Asn Lys Thr Asn 1700 1705 1710
Ala Glu Val Asp Arg Thr Glu Thr Asp Gly Asn Asp Asn lie Lys Val 1715 1720 1725 lie Leu Pro Lys Val Gin Val Lys Pro Ala Ala Arg Gin Ser Val Gly 1730 1735 1740
Val Lys Ala Glu Ala Gin Asn Ala Leu lie Asp Gin Ser Asp Leu Ser 1745 1750 1755 1760
Thr Glu Glu Glu Arg Leu Ala Ala Lys His Leu Val Glu Glo Ala Leu 1765 1770 1775
Asn Gin Ala lie Asp Gin lie Asn His Ala Asp Lys Thr Ala Gin Val 1780 1785 1790
Asn Gin Asp Ser lie Asn Ala Gin Asn lie lie Ser Lys lie Lys Pro 1795 1800 1805
Ala Thr Thr Val Lys Ala Thr Ala Leu Gin Gin lie Gin Asn lie Ala 1810 1815 1820
Thr Asn Lys lie Asn Leu lie Lys Ala Asn Asn Glu Ala Thr Asp Glu 1825 1830 1835 1840
Glu Gin Asn lie Ala lie Ala Gin Val Glu Lys Glu Leu lie Lys Ala 1845 1850 1855
Lys Gin Gin lie Ala Ser Ala Val Thr Asn Ala Asp Val Ala Tyr Leu 1860 1865 1870
Leu His Asp Glu Lys Asn Glu lie Arg Glu lie Glu Pro Val lie Asn 1875 1880 1885
Arg Lys Ala Ser Ala Arg Glu Gin Leu Thr Thr Leu Phe Asn Asp Lys 1890 1895 1900
Lys Gin Ala lie Glu Ala Asn lie Gin Ala Thr Val Glu Glu Arg Asn 1905 1910 1915 1920
Ser He Leu Ala Gin Leu Gin Asn lie Tyr Asp Thr Ala He Gly Gin 1925 1930 1935 lie Asp Gin Asp Arg Ser Asn Ala Gin Val Asp Lys Thr Ala Ser Leu 1940 1945 1950
Asn Leu Gin Thr lie His Asp Leu Asp Val His Pro lie Lys Lys Pro 1955 1960 1965
Asp Ala Glu Lys Thr He Asn Asp Asp Leu Ala Arg Val Thr Ala Leu 1970 1975 1980
Val Gin Asn Tyr Arg Lys Val Ser Asn Arg Asn Lys Ala Asp Ala Leu 1985 1990 1995 2000
Lys Ala lie Thr Ala Leu Lys Leu Gin Met Asp Glu Glu Leu Lys Thr 2005 2010 2015
Ala Arg Thr Asn Ala Asp Val Asp Ala Val Leu Lys Arg Phe Asn Val 2020 2025 2030
Ala Leu Ser Asp He Glu Ala Val lie Thr Glu Lys Glu Asn Ser Leu 2035 2040 2045
Leu Arg lie Asp Asn He Ala Gin Gin Thr Tyr Ala Lys Phe Lys Ala 2050 2055 2060 lie Ala Thr Pro Glu Gin Leu Ala Lys Val Lys Val Leu lie Asp Gin 2065 2070 2075 2080
Tyr Val Ala Asp Gly Asn Arg Met lie Asp Glu Asp Ala Thr Leu Asn 2085 2090 2095 -80- 119629-序列表.doc 200815028
Asp lie Lys Gin His Thr Gin Phe lie Val Asp Glu He Leu Ala lie 2100 2105 2110
Lys Leu Pro Ala Glu Ala Thr Lys Val Ser Pro Lys Glu He Gin Pro 2115 2120 2125
Ala Pro Lys Val Cys Thr Pro He Lys Lys Glu Glu Thr His Glu Ser 2130 2135 2140
Arg Lys Val Glu Lys Glu Leu Pro Asn Thr Gly Ser Glu Gly Met Asp 2145 2150 2155 2160
Leu Pro Leu Lys Glu Phe Ala Leu lie Thr Gly Ala Ala Leu Leu Ala 2165 2170 2175
Arg Arg Arg Thr Lys Asn Glu Lys Glu Ser 2180 2185 <210〉 76 <211> 773 <212> PRT <213〉葡萄球菌 <400〉 76
Glu Glu Asn Ser Val Gin Asp Val Lys Asp Ser Asn Thr Asp Asp Glu I 5 10 15
Leu Ser Asp Ser Asn Asp Gin Ser Ser Asp Glu Giu Lys Asn Asp Val 20 25 30 lie Asn Asn Asn Gin Ser lie Asn Thr Asp Asp Asn Asn Gin lie lie 35 40 45
Lys Lys Glu Glu Thr Asn Asn Tyr Asp Gly lie Glu Lys Arg Ser Giu 50 55 60
Asp Arg Thr Glu Ser Thr Thr Asn Val Asp Glu Asn Glu Ala Thr Phe 65 70 75 80
Leu Gin Lys Thr Pro Gin Asp Asn Thr His Leu Thr Glu Glu Glu Val 85 90 95
Lys Glu Ser Ser Ser Val Glu Ser Ser Asn Ser Ser He Asp Thr Ala 100 105 110
Gin Gin Fro Ser His Thr Thr He Asn Arg Glu Glu Ser Val Gin Thr 115 120 125
Ser Asp Asn Val Glu Asp Ser His Val Ser Asp Phe Ala Asn Ser Lys 130 135 140
He Lys Glu Ser Asn Thr Glu Ser Gly Lys Glu Glu Asn Thr lie Glu 145 150 155 160
Gin Pro Asn Lys Val Lys Glu Asp Ser Thr Thr Ser Gin Pro Ser Gly 165 170 175
Tyr ThrAsn lie Asp Glu Lys lie Ser Asn Gin Asp Glu Leu Leu Asn 180 185 190
Leu Pro lie Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu Ser Thr Thr 195 200 205
Ser Ala Gin Pro Ser lie Lys Arg Val Thr Val Asn Gin Leu Ala Ala 210 215 220
Glu Gin Gly Ser Asn Val Asn His Leu lie Lys Val Thr Asp Gin Ser 225 230 235 240 lie Thr Glu Gly Tyr Asp Asp Ser Glu Gly Val lie Lys Ala His Asp 245 250 255
Ala Glu Asn Leu lie Tyr Asp Val Thr Phe Glu Val Asp Asp Lys Val 260 265 270
Lys Ser Gly Asp Thr Met Thr Val Asp He Asp Lys Asn Thr Val Pro 275 280 285
Ser Asp Leu Thr Asp Ser Phe Thr lie Pro Lys lie Lys Asp Asn Ser 290 295 300
Gly Glu lie lie Ala Thr Gly Thr Tyr Asp Asn Lys Asn Lys Gin lie 305 310 315 320
Thr Tyr Thr Phe Thr Asp Tyr Val Asp Lys Tyr Glu Asn lie Lys Ala 325 330 335
His Leu Lys Leu Thr Ser Tyr lie Asp Lys Ser Lys Val Pro Asn Asn 340 345 350
Asn 了hr Lys Leu Asp Val Glu Tyr Lys Thr Ala Leu Ser Ser Val Asn 355 360 365
Lys Thr lie Thr Val Glu Tyr Gin Arg Pro Asn Glu Asn Arg Thr Ala 370 375 380
Asn Leu Gin Ser Met Phe Thr Asn lie Asp Thr Lys Asn His Thr Val 385 390 395 400
Glu Gin Thr lie Tyr lie Asn Pro Leu Arg Tyr Ser Ala Lys Glu Thr 405 410 415
Asn Val Asn He Ser Gly Asn Gly Asp Glu Gly Ser Thr lie lie Asp 420 425 430 • Asp Ser Thr He lie Lys Val Tyr Lys Val Gly Asp Asn Gin Asn Leu 81- 119629·序列表.doc 200815028 435 440 445
Pro Asp Ser Asn Arg lie Tyr Asp Tyr Ser Glu Tyr Glu Asp Val Thr 450 455 460
Asn Asp Asp Tyr Ala Gin Leu Gly Asn Asn Asn Asp Val Asn lie Asn 465 470 475 480
Phe Gly Asn He Asp Ser Pro Tyr lie He Lys Val He Ser Lys Tyr 485 490 495
Asp Pro Asn Lys Asp Asp Tyr Thr Thr lie Gin Gin Thr Val Thr Met 500 505 510
Gin Thr Thr lie Asn Glu Tyr Thr Gly Glu Phe Arg Thr Ala Ser Tyr 515 520 525
Asp Asn Thr lie Ala Phe Ser Thr Ser Ser Gly Gin Gly Gin Gly Asp 530 535 540
Leu Pro Pro Glu Lys Thr Tyr Lys He Gly Asp Tyr Val Trp Glu Asp 545 550 555 560
Val Asp Lys Asp Gly lie Gin Asn Thr Asn Asp Asn Glu Lys Pro Leu 565 570 575
Ser Asn Val Leu Val Thr Leu Thr Tyr Pro Asp Gly Thr Ser Lys Ser 580 585 590
Val Arg Thr Asp Glu Asp Gly Lys Tyr Gin Phe Asp Gly Leu Lys Asn 595 600 605
Gly Leu Thr Tyr Lys lie Thr Phe Glu Thr Pro Glu Gly Tyr Thr Pro 610 615 620
Thr Leu Lys His Ser Gly Thr Asn Pro Ala Leu Asp Ser Glu Gly Asn 625 630 635 640
Ser Val Trp Val Thr lie Asn Gly Gin Asp Asp Met Thr lie Asp Ser
645 650 655
Gly Phe Tyr Gin Thr Pro Lys Tyr Ser Leu Gly Asn Tyr Val Trp Tyr 660 665 670
Asp Thr Asn Lys Asp Gly lie Gin Gly Asp Asp Glu Lys Gly lie Ser 675 680 685
Gly Val Lys Val Thr Leu Lys Asp Glu Asn Gly Asn lie lie Ser Thr 690 695 700
Thr Thr Thr Asp Glu Asn Gly Lys Tyr Gin Phe Asp Asn Leu Asn Ser 705 710 715 720
Gly Asn Tyr He Val His Phe Asp Lys Pro Ser Gly Met Thr Gin Thr 725 730 735
Thr Thr Asp Ser Gly Asp Asp Asp Glu Gin Asp Ala Asp Gly Glu Glu 740 745 750
Val His Val Thr lie Thr Asp His Asp Asp Phe Ser lie Asp Asn Gly 755 760 765
Tyr Tyr Asp Asp Glu 770
〈210〉 87 <211〉 774 <212〉 PRT <213>葡萄球菌 <400> 87 .
Met Glu Glu Asn Ser Val Gin Asp Val Lys Asp Ser Asn Thr Asp Asp 1 5 10 15
Glu Leu Ser Asp Ser Asn Asp Gin Ser Ser Asp Glu Glu Lys Asn Asp 20 25 30
Val lie Asn Asn Asn Gin Ser lie Asn Thr Asp Asp Asn Asn Gin lie 35 40 45 lie Lys Lys Glu Glu Thr Asn Asn Tyr Asp Gly lie Glu Lys Arg Ser 50 55 60
Glu Asp Arg Thr Glu Ser Thr Thr Asn Val Asp Glu Asn Glu Ala Thr 65 70 75 80
Phe Leu Gin Lys Thr Pro Gin Asp Asn Thr His Leu Thr Glu Glu Glu 85 90 95
Val Lys Glu Ser Ser Ser Val Glu Ser Ser Asn Ser Ser He Asp Thr 100 105 110
Ala Gin Gin Pro Ser His Thr Thr lie Asn Arg Glu Glu Ser Val Gin 115 120 125
Thr Ser Asp Asn Val Glu Asp Ser His Val Ser Asp Phe Ala Asn Ser 130 135 140
Lys He Lys Glu Ser Asn Thr Glu Ser Gly Lys Glu Glu Asn Thr lie 145 150 155 160
Glu Gin Pro Asn Lys Val Lys Glu Asp Ser Thr Thr Ser Gin Pro Ser 165 170 175 -82- 119629-序列表.doc 200815028
Gly Tyr Thr Asn lie Asp Glu Lys lie Ser Asn Gin Asp Glu Leu Leu 180 185 190
Asn Leu Pro lie Asn Glu Tyr Glu Asn Lys Ala Arg Pro Leu Ser Thr 195 200 205
Thr Ser Ala Gin Pro Ser lie Lys Arg Val Thr Val Asn Gin Leu Ala 210 215 220
Ala Glu Gin Gly Ser Asn Val Asn His Leu lie Lys Val Thr Asp Gin 225 230 235 240
Ser lie Thr Glu Gly Tyr Asp Asp Ser Glu Gly Val lie Lys Ala His 245 250 255
Asp Ala Glu Asn Leu lie Tyr Asp Val Thr Phe Glu Val Asp Asp Lys 260 265 270
Val Lys Ser Gly Asp Thr Met Thr Val Asp He Asp Lys Asn Thr Val 275- 280 285
Pro Ser Asp Leu Thr Asp Ser Phe Thr He Pro Lys He Lys Asp Asn 290 295 300
Ser Gly Glu lie lie Ala Thr Gly Thr Tyr Asp Asn Lys Asn Lys Gin 305 310 315 320 lie Thr Tyr Thr Phe Thr Asp Tyr Val Asp Lys Tyr Glu Asn He Lys 325 330 335
Ala His Leu Lys Leu Thr Ser Tyr lie Asp Lys Ser Lys Val Pro Asn 340 345 350
Asn Asn Thr Lys Leu Asp Val Glu Tyr Lys Thr Ala Leu Ser Ser Val 355 360 365
Asn Lys Thr lie Thr Val Glu Tyr Gin Arg Pro Asn Glu Asn Arg Thr 370 375 380
Ala Asn Leu Gin Ser Met Phe Thr Asn lie Asp Thr Lys Asn His Thr 385 390 395 400
Val Glu Gin Thr He Tyr lie Asn Pro Leu Arg Tyr Ser Ala Lys Glu 405 410 415
Thr Asn Val Asn He Ser Gly Asn Gly Asp Glu Gly Ser Thr lie lie 420 425 430
Asp Asp Ser Thr lie lie Lys Val Tyr Lys Val Gly Asp Asn Gin Asn 435 440 445
Leu Pro Asp Ser Asn Arg lie Tyr Asp Tyr Ser Glu Tyr Glu Asp Val 450 455 460
Thr Asn Asp Asp Tyr Ala Gin Leu Gly Asn Asn Asn Asp Val Asn He 465 470 475 480
Asn Phe Gly Asn lie Asp Ser Pro Tyr He lie Lys Val lie Ser Lys 485 490 495
Tyr Asp Pro Asn Lys Asp Asp Tyr Thr Thr lie Gin Gin Thr Val Thr 500 505 510
Met Gin Thr Thr lie Asn Glu Tyr Thr Gly Glu Phe Arg Thr Ala Ser 515 520 525
Tyr Asp Asn Thr He Ala Phe Ser Thr Ser Ser Gly Gin Gly Gin Gly 530 535 540
Asp Leu Pro Pro Glu Lys Thr Tyr Lys lie Gly Asp Tyr Val Trp Glu 545 550 555 560
Asp Val Asp Lys Asp Gly lie Gin Asn Thr Asn Asp Asn Glu Lys Pro 565 570 575
Leu Ser Asn Val Leu Val Thr Leu Thr Tyr Pro Asp Gly Thr Ser Lys 580 585 590
Ser Val Arg Thr Asp Glu Asp Gly Lys Tyr Gin Phe Asp Gly Leu Lys 595 600 605
Asn Gly Leu Thr Tyr Lys lie Thr Phe Glu Thr Fro Glu Gly Tyr Thr 610 615 620
Pro Thr Leu Lys His Ser Gly Thr Asn Pro Ala Leu Asp Ser Glu Gly 625 630 635 640
Asn Ser Val Trp Val Thr lie Asn Gly Gin Asp Asp Met Thr He Asp 645 650 655
Ser Gly Phe Tyr Gin Thr Pro Lys Tyr Ser Leu Gly Asn Tyr Val Trp 660 665 670
Tyr Asp Thr Asn Lys Asp Gly lie Gin Gly Asp Asp Glu Lys Gly He 675 680 685
Ser Gly Val Lys Val Thr Leu Lys Asp Glu Asn Gly Asn lie He Ser 690 695 700
Thr Thr Thr Thr Asp Glu Asn Gly Lys Tyr Gin Phe Asp Asn Leu Asn 70S 710 715 720
Ser Gly Asn Tyr lie Val His Phe Asp Lys Pro Ser Gly Met Thr Gin 725 730 735
Thr Thr Thr Asp Ser Gly Asp Asp Asp Glu Gin Asp Ala Asp Gly Glu 740 745 750
Glu Val His Val Thr lie Thr Asp His Asp Asp Phe Ser lie Asp Asn 755 760 765 -83- 119629-序列表.doc 200815028
Gly Tyr Tyr Asp Asp Glu 770 <210> 88 <211〉 128 <212〉 PRT <213〉葡麟菌 <400〉 88
Met Asp Val Asn Thr Val Asn Gin Lys Ala Ala Ser Val Lys Ser Thr 15 10 15
Lys Asp Ala Leu Asp Gly Gin Gin Asn Leu Gin Arg Ala Lys Thr Glu 20 25 30
Ala Thr Asn Ala lie Thr His Ala Ser Asp Leu Asn Gin Ala Gin Lys 35 40 45
Asn Ala Leu Thr Gin Gin Val Asn Ser Ala Gin Asn ¥al His Ala Val 50 55 60
Asn Asp lie Lys Gin Thr Thr Gin Ser Leu Asn Thr Ala Met Thr Gly 65 70 75 80
Leu Lys Arg Gly Val Ala Asn His Asn Gin Val Val Gin Ser Asp Asn 85 90 95
Tyr Val Asn Ala Asp Thr Asn Lys Lys Asn Asp Tyr Asn Asn Ala Tyr 100 105 110
Asn His Ala Asn Asp lie He Asn Gly Asn Ala Gin His Pro Val lie 115 120 125
84- 119629-序列表.doc

Claims (1)

  1. 200815028 十、申請專利範圍: 1. 一種用於使N-乙醯化少於40%之PNAG與載體蛋白共軛之 方法,其包含以下步驟: a) 藉由添加包含順丁烯二醯亞胺基之鍵聯劑來活化該 PNAG以形成活化之PNAG ; b) 藉由添加包含酼基之鍵聯劑來活化該載體蛋白以形 成活化之載體蛋白;及 ^ c)使該活化之PNAG與該活化之載體蛋白反應以形成 φ PNAG-载體蛋白共軛物。 2. —種用於使N·乙醯化少於40%之PNAG與載體蛋白共軛之 方法,其包含以下步驟: a) 藉由添加包含巯基之鍵聯劑來活化該PNAG以形成活 化之PNAG ; b) 藉由添加包含順丁烯二醯亞胺基之鍵聯劑來活化該 載體蛋白以形成活化之載體蛋白;及 c) 使該活化之PNAG與該活化之載體蛋白反應以形成 • PNAG·載體蛋白共軛物。 3. 一種用於使N-乙醯化少於40%之PNAG與載體蛋白共軛之 - 方法,其包含以下步驟: . a)藉由添加包含巯基之鍵聯劑來活化該PNAG以形成活 化之PNAG ; b) 藉由添加包含酼基之鍵聯劑來活化該載體蛋白以形 成活化之載體蛋白;及 c) 使該活化之PNAG與該活化之載體蛋白反應以形成 119629.doc 200815028 PNAG-載體蛋白共軛物。 4. 如請求項1之方法,其中在步驟a)中該包含順丁烯二醯亞 胺基之鍵聯劑連接至PNAG上之胺基。 5. 如請求項2之方法,其中在步驟b)中該包含順丁烯二醯亞 胺基之鍵聯劑連接至該載體蛋白上之胺基。 v 6.如請求項1、2、4及5中任一項之方法,其中該包含順丁 烯二醯亞胺基之鍵聯劑係選自由BMPS、EMCS、 GMBS、MBS、LC-SMCC、SMCC、SMPB、SMPH、磺 # 基-EMCS、磺基-MBS、磺基-SMCC、磺基-GMBS及磺 基-SMPB組成之群。 7. 如請求項6之方法,其中該包含順丁烯二醯亞胺基之鍵 聯劑為GMBS或磺基-GMBS。 8. 如請求項1-5中任一項之方法,其中在步驟a)期間PNAG 與該包含順丁烯二醯亞胺基之鍵聯劑之重量/重量比率為 1:20-2:1 〇 9. 如請求項1-5中任一項之方法,其中該藉由添加包含順丁 _ 燁二醯亞胺基之鍵聯劑之活化步驟係在6·0-8·5之pH值下 進行。 、. 10.如請求項1、3及4中任一項之方法,其中在步驟b)中該包 、 含巯基之鍵聯劑連接至該載體蛋白上之胺基。 11.如請求項1-5中任一項之方法,其中該包含酼基之鍵聯劑 係選自由 SPDP、LC-SPDP、SMPT、LC-SMPT、磺基-SPDP、磺基-SMPT、磺基-LC-SMPT、磺基-LC-SPDP及 N-乙醯基同型半胱胺酸硫内酯組成之群。 119629.doc 200815028 12. 如請求項11之方法,其中該包含巯基之鍵聯劑為SPDP或 LC-SPDP 〇 13. 如請求項11之方法,其中該包含巯基之鍵聯劑具有5-10 埃之間隔長度。 14. 如請求項11之方法,其中該包含巯基之鍵聯劑具有10-25 或15-20埃之間隔長度。 15. 如請求項1-5中任一項之方法,其中在該藉由添加包含酼 基之鍵聯劑之活化步驟期間,該包含巯基之鍵聯劑與該 載體蛋白或PNAG之重量/重量比率為1〇〇:1-1〇:1。 16. 如請求項1-5中任一項之方法,其中該藉由添加包含巯基 之鍵聯劑之活化步驟係在6.0-9.0之pH值下進行。 17. 如請求項1-5中任一項之方法,其中在步驟c)期間活化之 PNAG與該活化之載體蛋白之重量/重量比率為4:1-1:4。 18·如請求項1-5中任一項之方法,其中步驟c)係在6·0-9·0之 pH值下進行。 19·如請求項1-5中任一項之方法,其包含用半胱胺酸阻斷過 量之活化基團之另一步驟d)。 20·如請求項1-5中任一項之方法,其中該載體蛋白係選自由 以下組成之群:破傷風類毒素、白喉類毒素、 CRM197、rEPA、蛋白 D、SitC/MntC/唾液結合蛋白、 EbhA、EbhB、彈性蛋白結合蛋白(EbpS)、EFB(FIB)、 SBI、ClfA、SdrC、SdrG、SdrH、脂肪酶<^11〇、8如八、 FnbA、FnbB、Cna、ClfB、FbpA、Npase、IsaA/PisA、 SsaA、EPB、SSP-1、SSP-2、HBP、玻璃連接蛋白、血 119629.doc 200815028 纖維蛋白原結合蛋白、凝固酶、Fig、MAP、IsdA、 IsdB、HarA、SitC、α毒素(Hla)、α毒素 H35R 突變體、 MRPII及自溶素或其片段。 21. —種用於製造疫苗之方法,其包含進行如請求項1-20中 任一項之方法及合併該PNAG-載體蛋白共軛4勿與醫藥學 上可接受之賦形劑之另一步驟。 22·如請求項21之方法,其包含合併該PNAG-載體蛋白共輛 物與額外抗原之另一步驟。 23·如請求項22之方法,其中該(等)額外抗原包含細菌多醣 或募醣。 24.如請求項23之方法,其中該額外抗原包含來自5及/或8型 金黃色葡萄球菌awrews)之英膜多酷或寡 醣。 25·如請求項22或23之方法,其中該(等)額外抗原包含來自 金黃色葡萄球菌之3 3 6抗原。 26·如請求項22-24中任一項之方法,其中該(等)額外抗原包 含葡萄球菌蛋白或其片段。 27·如請求項26之方法,其中該葡萄球菌蛋白或其片段包含 與SEQ ID NO : 1至33、67至76、87及88中任一序列之胺 基酸序列至少80%相同之胺基酸序列。 28.如請求項21-24中任一項之方法,其中該PNAG-載體蛋白 共輛物係與佐劑合併。 29· —種PNAG-載體蛋白共軛物,其可藉由如請求項1-20中 任一項之方法獲得。 119629.doc 200815028 30· —種PNAG-載體蛋白共軛物,其中該PNAG少於40% N-乙醯化,且該PNAG與該載體蛋白係藉由包含鍵結硫原 子之順丁烯二醯亞胺基之鍵聯劑接合。 31·如請求項30之PNAG-載體蛋白共輛物,其中該順丁烯二 醯亞胺基係位於該PNAG與該硫原子之間。 ν 32·如請求項30之PNAG-載體蛋白共軛物,其中該順丁烯二 醯亞胺基係位於該載體蛋白與該硫原子之間。 33.如請求項30之PNAG-載體蛋白共軛物,其具有如下結 ⑩ 構: PNAG
    \載體蛋白 其中R1及R2係獨立選自視情況經取代之芳族鏈或脂肪鏈 或一鍵。
    34·如請求項30之PNAG-載體蛋白共軛物,其具有如下結 構:
    載體蛋白
    PNAG 其中R1及R2係獨立選自視情況經取代之芳族鏈或脂肪鏈 或一鍵。 119629.doc 200815028 35. —種PNAG-載體蛋白共軛物,其中該PNAG少於40% N-乙醯化,且該PNAG與該載體蛋白係藉由包含鍵結至硫 原子之硫原子之鍵聯劑接合。 36·如請求項35之PNAG-載體蛋白共軛物,其具有如下結 構:
    其中R1及R2係獨立選自視情況經取代之芳族鏈或脂肪鏈 或一鍵。 37·如請求項33、34或36之PNAG-載體蛋白共軛物,其中R1 為C1-C6烷基。 38.如請求項33、34或36之PNAG-載體蛋白共輒物,其中R2 為C1-C6烷基。 39·如請求項37之PNAG-載體蛋白共軛物,其中R2為C1-C6 烧基。 40·如請求項34之PNAG-載體蛋白共軛物,其具有如下結 構:
    41. 一種N-乙醯化少於40%之活化之PNAG,其中該PNAG共 119629.doc
    200815028 價鍵結至包含順丁烯二醯亞胺基之鍵聯劑。 42.如請求項41之活化之PNAG,其具有如下結構: Ο
    其中R1係選自視情況經取代之芳族鏈或脂肪鏈(例如C1-C6或C3烷基)或一鍵。 43. —種疫苗,其包含如請求項29-40中任一項之PNAG-載體 蛋白共軛物及醫藥學上可接受之賦形劑。 44. 如請求項29-36及40中任一項之PNAG-載體蛋白共軛物, 其係用於治療或預防葡萄球菌疾病。 45. —種如請求項29-40中任一項之PNAG-載體蛋白共軛物之 用途,其係用於製備供治療或預防葡萄球菌疾病之疫 苗。
    119629.doc 200815028 七、 指定代表圖: (一) 本案指定代表圖為:(無) (二) 本代表圖之元件符號簡單說明: 八、 本案若有化學式時,請揭示最能顯示發明特徵的化學式: (無)
    119629.doc
TW096111419A 2006-03-30 2007-03-30 共軛方法 TWI425951B (zh)

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