CN109963586A - 作为抗疟疾疫苗的生物融合蛋白 - Google Patents
作为抗疟疾疫苗的生物融合蛋白 Download PDFInfo
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Abstract
本发明涉及包括至少一个融合至载体异源蛋白序列的抗原性氨基酸序列的融合蛋白，其中所述抗原性序列包括疟原虫属(Plasmodium)蛋白的表位序列且所述载体异源蛋白序列是在人类中具有免疫原性的序列。所述蛋白可用作抗疟疾疫苗。
Description
本发明涉及对抗疟疾的保护，更特定而言涉及包括融合蛋白的疟疾疫苗。
背景技术
造成人类疟疾的寄生虫，尤其包含恶性疟原虫(Plasmodium falciparum)，在人类宿主中展现不同形态且随其在所感染宿主的生物体中的定位不同而表达不同抗原。这些寄生虫在它们的生命循环期间在人体内的形态和抗原性差异使得能够具有至少4个不同发育阶段。寄生虫在人类中的最初发育阶段对应于通过寄生虫的昆虫载体的叮咬引入宿主血液中的子孢子形式。第二阶段对应于寄生虫通过肝且感染肝细胞，其中寄生虫发育形成肝裂殖体，所述肝裂殖体在其成熟(例如，在恶性疟原虫的情形下，在子孢子侵入后第6天)时通过破裂释放肝裂殖子。第三阶段的特征在于在成熟时释放游离裂殖子的寄生虫的无性形式(血液阶段裂殖体)感染血液红细胞；此红细胞发育阶段对应于疾病的病原期。第四阶段对应于形成具有性潜力的形式(或配子母细胞)，所述形式将变成细胞外性形式或蚊子中的配子。
并无引入临床实践中的实践或有效疫苗。
疟疾亚单位疫苗迄今为止已展示免疫原性的重大缺陷。所观察到的免疫反应效价低且持续时间短。已探究各种方式来解决此缺陷，包含选择佐剂、在诸如病毒样颗粒(VLP)、腺病毒载体等复合载体中表达和设置复杂初免-加强方案。即使使用来自恶性疟原虫疟疾寄生虫的红细胞前环子孢子蛋白(CSP)和乙型肝炎病毒的病毒包膜蛋白(HBsAg)中的重复序列和T细胞表位的基因和复杂佐剂如ASO1所工程化改造的RTS,S/AS01疫苗亦受困于疟疾特异性免疫反应的极短持续时间(而乙型肝炎反应长时间保持较高)。
还揭示了疟原虫属(Plasmodium)抗原至载体蛋白的化学偶联。举例而言，包括偶联至铜绿假单胞菌(Pseudomonas aeruginosa)胞外蛋白A(repA)的去毒形式的疟原虫属蛋白Pfs25H的疫苗正处于评估中。
然而，化学偶联具有若干缺点。其在技术上需求较高，难以再现，且相当昂贵。
仍亟需展示良好免疫原性和对抗疟疾的保护同时易于复制并负担得起的疫苗产品。
发明内容
本发明提供源于由与载体蛋白如CRM197融合的疟原虫属多肽组成的新颖构建体的改良免疫原性的优点。并非以化学方式使疟原虫属分子偶合至载体蛋白，发明者研发一种新方式，其中将寄生虫蛋白与载体蛋白一起编码为融合蛋白，从而制备“生物偶联的融合产物”，其在本文中也称为“生物融合分子”且可以以重组方式在例如大肠杆菌(E.coli)中产生。
更特定而言，本发明提供包括至少一个融合于载体异源蛋白序列的N-末端和/或C-末端的抗原性氨基酸序列的融合蛋白，其中所述抗原性序列包括疟原虫属蛋白的表位序列且所述载体异源蛋白序列是在人类中具有免疫原性的序列。
抗原性序列可以是由红细胞阶段的疟原虫属所表达的抗原性蛋白或其表位片段。
或者，抗原性序列可以是由红细胞前阶段的疟原虫属所表达的抗原性蛋白或其表位片段。
本发明的另一目标是编码如本文所定义的融合蛋白的核酸构建体。
还提供在表达盒中包括所述核酸构建体的载体以及其中插入所述载体的宿主细胞。
另外阐述了制备融合蛋白的体外方法，所述方法包括使宿主细胞在诱导核酸构建体表达的条件下繁殖，且收集如此表达的融合蛋白。
根据本发明，提供一种疫苗，其包括所述融合蛋白或至少两种分别包括至少两种不同抗原性氨基酸序列的融合蛋白的组合或编码所述融合蛋白的核酸构建体，与生理上可接受的媒剂。
所述疫苗可用于向人类对象接种疫苗，来对抗疟疾。
附图说明
图1是PP21(也称为生物融合体MSP3-1)的编码序列的图式。下面显示的碱基对的标度自Nco I位点开始。
图2展示pET26a-PP21质粒图(A)、通过使用Sma I(B)或Eco R I(C)进行限制酶消化的小量制备分析。
图3：通过IMAC纯化的重组蛋白PP21。(A)通过电泳在变性条件和考马斯蓝色染(Coomassie blue)下进行的分析。(B)通过蛋白质印记(Western blotting)使用鼠类抗MSP3免疫血清在1:1000稀释下评价的抗原性。观察到的上区带与全长PP21的84kDa的理论分子量一致。37kDa处的另一带在较小程度上由抗MSP3免疫血清识别，可对应于PP21的降解片段。
图4：通过蛋白质印记使用抗MSP3-1mAb RAM1在1:1000稀释下评价的在不同储存温度下的PP21稳定性的时间量表。
图5：与阳性对照MSP3-LSP相比所测定的PP21抗原含量。通过与大量人类和动物抗MSP3血清包含人类重组抗体的反应性来测定临床前PP21的抗原性。抗原含量提供反应性表位的量的较精确量度。其通过用于Elisa分析中的涂层的抗原连续稀释液来实施且通过充分限定的阳性对照(此处是通过MSP3的C-末端区域免疫化的大鼠的集合)予以揭示。PP21的反应性与MSP3合成和重组构建体相同。
图6：在通过生物融合体MSP3-1偶联物免疫化2次后于小鼠中所诱导的特异性抗体反应与当前MSP3-1-LSP相比的显著改良。使用于Montanide ISA720中的仅1μg生物融合体MSP3-1或10μg MSP3-1LSP在第0、14和28天对5只(BALB/c)或4只(C57BL/6)小鼠的组免疫化。在第2次注射后一周在第21天(A)和在第3次免疫化后一周在第35天收集血样。通过ELISA测定特异性MSP3-1 LSP抗体效价。单独展示每一小鼠(1至5)的结果(此处在仅两次免疫化后)。
图7：在通过生物融合体MSP3-1免疫化2次和3次后于小鼠中所诱导的抗体反应与当前MSP3-1-LSP的对比。第三次注射加强抗体反应且证实生物融合体MSP3-1在C57Bl/6小鼠和Balb/c小鼠中的更好免疫原性。通过1μg生物融合体MSP3-1的3次注射诱导的MSP3-1-LSP特异性抗体的平均效价在C57Bl/6和Balb/c中分别达到3×105和2×105；而10μg MSP3-1-LSP的3次注射在C57Bl/6和Balb/c小鼠中分别诱导最大105和2.5×104的平均效价。
图8：通过生物融合体MSP3-1在小鼠中所诱导的MSP3-1特异性抗体的持续时间与当前MSP3-1-LSP相比的重大改良。
A和B：生物融合体MSP3-CRM与MSP3-1-LSP的对比：使用于Montanide ISA720中的仅1μg生物融合体MSP3-1或10μg MSP3-1LSP在第0、14和28天对BALB/c(A-上左图)和C57BL/6(B-上右图)小鼠免疫化。在随访中的不同日期收集血样。通过ELISA测定特异性MSP3-1LSP抗体效价。所展示结果对应于在不同天数在每一组小鼠中所获得的抗MSP3-1 LSP抗体效价的几何平均值。在160天随访后，生物融合体-MSP3-1偶联物免疫小鼠中的平均抗体效价在C57bl/6和Balb/c中分别为1.5×105和105，其比通过MSP3-1-LSP诱导且在第一次免疫化后第160天测量的抗体的平均效价高至少10倍。
C和D：通过MSP3-CRM诱发的免疫反应的长期持久性：通过在第0、14和103天经皮下注射在Montanide ISA 720佐剂(v/v)中佐剂化的1μg生物融合体MSP3-CRM来对Balb/c和C57Bl6小鼠(4至5只小鼠/组)的组免疫化。在不同天数收集血样。通过ELISA测定特异性MSP3抗体效价。结果展示，在两次免疫化后效价显著增加且在第49天达到最大，而实施于第103天的第三次抗原注射不诱导抗体反应量值的任何可检测增加。所述特异性抗体仅随时间略微降低，且即使在免疫化后第540天仍可以以高效价检测到。
E：在仅2次免疫化后通过MSP3-CRM诱发的免疫反应的长期持久性。就在仅两次免疫化后观察的满意反应而言，在仅在第0和14天通过皮下注射使用2μg在Montanide ISA720(v/v)中佐剂化的生物融合体MSP3-CRM免疫化的其他17只Balb/c小鼠中分析此免疫化方案。在不同日期收集血样。通过ELISA测定特异性MSP3-1-LSP抗体效价。结果展示，MSP3抗体效价在两次抗原注射后有所增加且在所有小鼠中于第42与72天之间达到最大，且在380天实验随访中显示免疫反应仅中度降低。
图9：与MSP3-1-LSP相比，在使用生物融合体MSP3-1免疫化的小鼠中诱导的抗体对MSP3-1 ADCI(Ab依赖性细胞抑制)靶表位的改良识别。在MSP3-1-LSP中，肽“b”、“c”和“d”定义由在ADCI分析中有效的抗体靶向的不同B细胞表位，其与抗MSP3-1抗体的保护效应相关。为评估生物融合体MSP3-1诱导抗体靶向这些表位的能力，通过ELISA测定抗体对血清中的肽a、b、c和d的效价。因此，由新颖制剂识别的ADCI靶的数量相当大且具有较高效价。使用于Montanide ISA720中的仅1μg生物融合体MSP3-1或10μg MSP3-1 LSP在第0、14和28天将BALB/c和C57BL/6小鼠免疫化。在第3次免疫化后一周，即在第35天收集血样。以1/400稀释小鼠血清且通过ELISA测定不同MSP3-1肽(a、b、c和d)的特异性抗体的效价。所展示结果对应于使用每一测试小鼠的血清获得的光学密度。
图10：使用1μg生物融合体MSP3-1、10μg当前MSP3-1 LSP或10μg MSP3-1 C-末端重组蛋白免疫化的HIMM模型(人类免疫原性小鼠模型)中的人类抗体反应。向NOD.Cg-Prkdcscid-IL2rgtm1WjI/SzJ(NSG)小鼠中植入在体外经1μg/ml抗原刺激或未刺激的人类脾细胞(4只小鼠/组)。使每一NSG小鼠接受30×106个经抗原引发或未引发的脾细胞的腹膜腔内注射(ip)。在第7和21天，使用1μg生物融合体MSP3-1或10μg MSP3-1-LSP或10μg MSP3-1 C-末端重组蛋白对重建小鼠进行加强。使用Montanide ISA 720(v/v)将所有抗原佐剂化且经腹膜腔内(ip)进行注射。使用未引发脾细胞重建的小鼠仅接受佐剂。在每一免疫化后一周收集血样。通过总IgG和特异性IgG ELISA来分析特异性抗体。使用下式计算经调节的特异性抗体效价：(抗原特异性抗体效价/总人类IgG浓度)×10(10mg/ml可视为平均人类总IgG浓度)。表示出ELISA效价的几何平均值(95％CI)。
图11：使用1μg生物融合体MSP3-1、10μg当前MSP3-1 LSP或10μg MSP3-1 C-末端重组蛋白免疫化的HIMM模型(Hu淋巴NSG小鼠)中的人类IFN-γ细胞反应。免疫化条件与上文相同。通过IFN-γELISPOT评估细胞反应。在第28天，回收每一组小鼠的脾细胞，汇集且在体外使用或不使用抗原刺激进行培养。所展示结果对应于使用每一组小鼠获得的特异性斑点形成细胞(SFC)。
图12：HIMM中的T细胞反应：通过1μg生物偶联物PP21或10μg MSP3-LSP免疫化的小鼠中的移植人类淋巴细胞中的CD4-Th1反应的显著改良。
图13：在使用生物融合体MSP3-1免疫化的HIMM模型中诱发的人类抗体对寄生虫天然蛋白的改良识别。向NSG小鼠中植入人类脾细胞且使用1μg生物融合体MSP3-1、10μg当前MSP3-1 LSP或10μg MSP3-1 C-末端重组蛋白免疫化(如图6中所描述)。通过免疫荧光抗体测试(IFAT)在3D7恶性疟原虫(Pf)感染的红细胞上评估第28天小鼠血清中的人类抗体与寄生虫蛋白的反应性，其是在疟疾攻击期间活化ADCI防御机制的关键特征。所展示结果对应于使用每一组小鼠获得的效价范围。
图14：使用1μg生物融合体MSP3-1免疫化的HIMM模型中所诱发的人类抗体反应不取决于疫苗制剂中所使用的佐剂。(A)向NSG小鼠中植入衍生自两个不同供体且使用1μg经Montanide ISA720佐剂化的生物融合体MSP3-1进行刺激或并不刺激的人类脾细胞(如图6中所描述)(4只小鼠/组/供体)。(B)向NSG小鼠中植入使用1μg经MF59而非MontanideISA720佐剂化的生物融合体MSP3-1进行刺激(9只小鼠)或并不刺激(8只小鼠)的人类脾细胞(如图6中所描述，但使用来自不同供体的人类淋巴细胞)。在两种情形下，通过ELISA在第28天测定特异性MSP3-1 LSP抗体效价。所展示结果对应于使用每一组小鼠获得的ELISA效价的平均值±SD。
图15：使用经Montanide ISA720佐剂化的生物融合体MSP3-1免疫化的HIMM模型中的人类淋巴细胞中所诱发人类IgG抗体的抗体子类。向NSG小鼠中植入使用1μg MSP3生物融合体刺激或并不刺激的人类脾细胞(如图10中所描述)。以1/20稀释在第28天收集的小鼠血清。通过子类IgG ELISA测定特异性MSP3-1 LSP抗体效价。所展示结果对应于使用经免疫化小鼠和未免疫化小鼠获得的光学密度的平均值±SD。
图16：使用经MF59佐剂化的生物融合体MSP3-1免疫化的HIMM模型中所诱发人类IgG抗体的子类。向NSG小鼠中植入使用1μg经MF59佐剂化的生物融合体MSP3-1刺激或并不刺激的人类脾细胞(如图14中所描述)。以1/20稀释在第28天收集的小鼠血清。通过子类IgGELISA在反应小鼠的血清中测定特异性MSP3-1 LSP抗体效价。所展示结果对应于使用经免疫化小鼠和未免疫化小鼠获得的光学密度的平均值±SD。两种佐剂皆获得嗜细胞子类IgG1的主导性。
图17：0.2μg或1μg PP21在Balbc小鼠/PP21-montanide(上左和上右)或相同剂量在C57bl小鼠(下图左和下右图)中的免疫原性。如图6-8来测定抗MSP3-1-LSP抗体效价的演变。
图18：通过PP21诱发的抗MSP3-1抗体与MSP3蛋白质家族的其他成员的交叉反应性(通过ELISA测得的OD值)。使C57Bl/6(C)和Balb/c(B)小鼠接受4μg PP21的2次注射(J0、J14)。在第63天收集试样。
图19：由氢氧化铝佐剂化的PP21在C57BL(C)和Balb/C小鼠(B)中在1μg剂量/免疫化下的免疫原性。展示在2次免疫化或3次免疫化后通过ELISA在C57BL(C)和Balb/C小鼠(B)中测得的抗体效价。未测试高于25:600的稀释度。应注意，氢氧化铝在人类中是产生高Th1反应的强力佐剂，与之相反，其在啮齿类动物中通常是较差佐剂，且仍与PP21一起诱导强力反应。
图20：生物融合体偶联物PP21在南美松鼠猴中的高免疫原性。通过在第0、28和112天经皮下(SC)施用1μg由MontanideI Isa 720佐剂化的PP21对出生于Primate Center ofBelem,Brasil的动物屋中的笼中的南美松鼠猴进行免疫化(虚线，与仅接受Montanide的对照(直线)相比)。通过ELISA针对MSP3-LSP抗原以及通过IFAT和WB测定抗体(未展示)。即使在每次免疫化仅使用0.1μg抗原时，免疫反应约低5倍，即仍非常显著(未展示)。
图21：在接受1μg PP25与Montanide ISA720或10μg LSA3-729与MontanideISA720的Balb/C小鼠中通过LSA3-CRM(PP25)或LSA3-729所诱发的抗体反应。在第0、7、28天免疫化，在第45天收集血清。
图22：在LSA3-CRM(PP25)或LSA3-729免疫化Balb/C小鼠(在体外通过DG 729攻击)中所诱发的IFNγ(ELISPOT)。
图23：HIMM中的抗LSA3-729人类抗体反应和结果改良的再现性：使用来自两个人类供体《A》和《B》的淋巴细胞在HIMM中对LSA3-CRM构建体PP25的抗LSA3-729人类抗体反应。
图24：通过PP25诱发的免疫反应的持续时间的改善。
图25：研发用于HuH7.5中的恶性疟原虫肝阶段发育的新颖宿主细胞且与人类原代肝细胞(HPH)进行比较。所述图展示在感染子孢子后第4、5和7天肝裂殖体的代表性试样，其经小鼠多克隆抗PfHsp-70免疫染色。放大率：400倍，比例尺：10μm。在第7天于HPH中难以发现满意LS。然后将此肝细胞瘤模型用于功能分析中以测量能够抑制子孢子侵袭至肝细胞中的抗体。
图26：抗Pf LSA3抗体对Hu7.5肝细胞瘤细胞中的子孢子侵袭的抑制(ILSDA)。展示天然蛋白质上的抗LSA3反应性之间的关联(通过IFAT分析)以及肝阶发育期抑制分析(ILSDA)中的功能抑制效应。较小图形展示使用抗环子孢子mAb 2A10的相同分析。
图27：在HIMM模型中移植的人类淋巴细胞中通过构建体PP23(MSP3-2-CRMP97-MSP3-3)诱发强B和T细胞反应。上图(A)展示抗体反应，中间图(B)展示同型分布，其主要是IgG1类，主要嗜细胞类能够与ADCI机制中的单核细胞协同作用。下图(C)展示通过在体外由MSP3-2或MSP3-3再刺激的IFN-γ的分泌评估的T细胞反应。
图28：BALb/c小鼠(n＝5)中的1μg与10μg剂量的生物融合体LSA5-CRM/MontanideISA720相比的免疫原性。实验条件类似于图8中所描述的那些。在第0、14和28天(箭头)通过生物融合体LSA5-CRM/Montanide ISA720免疫化。通过ELISA滴定利用LSA5-LSP作为抗原使用在第0、7、21、42天收集的血清来实施血清抗体检测。
具体实施方式
定义
“疫苗”应理解为意指用以产生免疫性，以用于预防和/或治疗疾病的组合物。因此，疫苗是包括抗原的药剂，且旨在用于人类或动物中，通过接种疫苗而产生特定防御和保护性物质。本文所用的“疫苗”意指能够引起对疟疾的部分或完全保护的免疫原性组合物。疫苗可用于预防感染和/或用于在受感染个体中治疗感染。
术语“免疫原性”意指所提及的组合物或蛋白质能够在施用时诱发免疫反应。个体中的“免疫反应”是指对抗原产生适应性和/或先天性免疫反应，包含体液免疫反应、细胞免疫反应或体液与细胞免疫反应。“体液免疫反应”是指由抗体所介导的免疫反应。
本文件中所用的术语“保护”或“预防”是指在与疟原虫属寄生虫接触后不会出现症状或出现的疾病症状减少。特定而言，术语“预防疟疾”是指治疗对象在与造成疟疾的疟原虫属接触后，不会出现症状或出现的症状减少。
“患者”或“对象”通常是哺乳动物对象，优选是人类对象。所述对象可以是雄性或雌性、儿童或成人。所述对象可以是先前已诊断或鉴别为患有疟疾者。或者，所述对象也可以是过去未曾被诊断患有疟疾但处于发生所述病症的风险下，例如因感染或因在疟疾流行的区域内旅行。举例而言，所述对象可以是表现出一或多种疟疾症状者。
举例而言，所述对象可感染恶性疟原虫或间日疟原虫(Plasmodium vivax)。
原始多肽的“同源”或“实质上同源”序列通常是如下序列：其与原始多肽序列或原始多肽的免疫原性或表位片段具有至少约80％同一性，且实质上保留所述原始多肽对预期靶的期望效应(即诱发免疫原性反应或被抗体识别)。在越来越优选的实施例中，同源序列与原始多肽序列或其免疫原性或表位片段具有至少约85％、90％、95％、97％或99％的同一性。
“免疫原性片段”通常具有至少5个氨基酸的长度。越优选地，免疫原性片段的长度为至少7、9、11、13、15、17和19个氨基酸。“表位”通常具有至少5个氨基酸，优选为至少7至14个氨基酸的长度。“表位片段”包括这种表位且因此可以更长。
在本发明的上下文中，术语“融合或生物融合”意指在重组蛋白中，载体蛋白直接连接至抗原性疟原虫属序列，或通过肽连接体连接至抗原性疟原虫属序列。所述肽连接体可以是1至35个氨基酸，优选为5至20个氨基酸，更优选为5至10个氨基酸的序列。在优选实施方式中，连接体肽是(Gly-Gly-Gly-Gly-Ser)n、(Gly)n或(EAAAK)n，其中n为1至4，优选为1至3。在任何实施方式中，形成单一多肽。
载体蛋白
载体异源蛋白序列可有利地选自：白喉类毒素的交叉反应材料(CRM)、白喉类毒素(D)、铜绿假单胞菌胞外蛋白A的无毒突变重组体(repA)、脑膜炎球菌外膜蛋白复合物(OMPC)、破伤风类毒素(T)、流行性感冒嗜血杆菌蛋白D(H.influenza protein D，hiD)及其免疫原性片段。
在优选实施方式中，载体异源蛋白序列可以是CRM197或其免疫原性片段，所述片段优选地选自：CRM197的片段A、跨膜结构域T、受体结合结构域R、CRM197的氨基酸序列1-190和CRM197的氨基酸序列1-389。
白喉毒素的片段A自氨基酸1延伸至201。CRM197拥有酶促惰性片段A，所述片段显示甘氨酸52被谷氨酸替换。
白喉毒素的片段B自氨基酸202延伸至535。
表1下面展示关于特定载体的其他信息。
也可使用实质上同源序列。
抗原性疟原虫属序列
本发明的融合蛋白构建体包括至少一个包含疟原虫属蛋白的表位序列的抗原性序列。
所述抗原性序列可以是来自任何疟原虫属物种的任何疟原虫属抗原的序列。
感染人类的寄生虫的“疟原虫属”包括(但不限于)恶性疟原虫、间日疟原虫、诺氏症原虫(P.knowles)、卵形疟原虫(P.ovale)和三日疟原虫(P.malariae)。下文所列示的抗原主要是来自恶性疟原虫的抗原。然而，也涵盖其他疟原虫属物种中的直系同源物。特定而言，间日疟原虫抗原与恶性疟原虫抗原展示相同的低免疫原性。
所述抗原可表达于红细胞阶段(也称为血液阶段)或红细胞前阶段(子孢子和肝阶段)中。
可使用的抗原性序列的实例列示于下表2中。也可使用实质上同源序列。
表达于红细胞阶段中且作为Ab依赖性细胞抑制(ADCI)防御机制的靶的抗原包含：
MSP3(例如MSP3-1、MSP3-2、MSP3-3、MSP3-4、MSP3-7、MSP3-8)、11-1的PEBS子区(也称为LSA5)、Glurp R0和R2、SERP、P27和P27A、P45、P90和P77、P14、P181(其是P77的组合)、MSP1-区2、MSP2(两个3D7和FC27等位基因，二者皆是二态和恒定区域)、GBP 130(尤其N和C部分二者)、蛋白质332、蛋白质11-1、MSP4或其任何表位片段。
优选地，融合蛋白中的抗原性序列系MSP3或其表位片段。
在另一优选实施方式中，融合蛋白中的抗原性序列系LSA5或其表位片段。
恶性疟原虫裂殖子表面蛋白3(MSP-3)是已知无性血液阶段疟疾疫苗候选抗原(Sirima等人，N Engl J Med 2011,365(11):1062-1064；Demanga等人，Infect Immun2010,78(1):486-494；Daher等人，Infect Immun 2010,78(1):477-485；Rousillon等人、Roussilhon等人，PLoS Medicine，2007年11月4日，第11期，e320)。
特定而言，可使用6种MSP3蛋白中的任一种，优选为MSP3-1以及蛋白质的肽a、b、c、d、e、f、重组体C-末端以及全长和N-末端。在优选实施方式中，抗原性序列是MSP3或其表位片段，所述片段涵盖选自MSP3-1、MSP3-2、MSP3-3、MSP3-4、MSP3-7、MSP3-8的疟原虫属MSP3蛋白的C-末端区域的基序a、b、c、d、e和/或f。
涵盖来自裂殖子表面的其他抗原、尤其是松散附接或裂解且由此可自裂殖子表面释放的那些。
表达于红细胞前阶段中的抗原包含LSA3、PEBS、CS、Trap和Salsa及其任何表位片段。在恶性疟原虫中，肝阶段抗原-3(LSA-3)是表达于红细胞前阶段的抗原(Toure-Balde等人：Infect Immun 2009,77(3):1189-1196；Daubersies等人：Nat Med 2000,6(11):1258-1263)。
也涵盖涉及其他阶段或其他机制的抗原。那些抗原包含涉及有性阶段的抗原如Pf25或Pf45/48，和涉及红细胞中的裂殖子侵袭抑制的GIA机制的血液阶段抗原如Rh5、AMA1、MSP1-19、MSP1-42、MSP2或MSP4-5，或涉及细胞黏附的抗原如Var CSA。
表2：抗原性序列(恶性疟原虫)
#指与上一列相同的参考
融合构建体
在特定实施方式中，融合蛋白包括融合至作为载体序列的CRM197或其免疫原性片段的、作为抗原性序列的MSP3(优选地MSP3-1)、LSA3、LSA5(也称为PEBS)或其表位片段，或由其组成。
在优选方面，融合蛋白包括两个抗原性序列，所述抗原性序列各自位于载体蛋白序列的C-末端和N-末端，或二者皆位于同一末端，其中两个抗原性序列彼此相同或不同。
在优选实施方式中，抗原性序列与载体序列之间的融合是直接融合。
在另一实施方式中，所述至少一个氨基酸序列可通过肽连接体连接于载体异源蛋白序列的N-末端和/或C-末端，其中所述肽连接体优选是1至35个氨基酸，优选为5至20个氨基酸的序列。在优选方面，所述肽连接体是(Gly-Gly-Gly-Gly-Ser)n、(Gly)n或(EAAAK)n，其中n为1至4，优选为1至3。
核酸、载体和宿主细胞
可通过任何重组技术来制备本发明的融合蛋白。因此，本发明的另一方面涉及含有编码所述融合蛋白的核酸的载体，优选为表达载体。
本发明中所使用的表达载体可提供体外和/或体内表达(例如在适宜宿主细胞、宿主生物体和/或表达系统中)。他们通常包括如上文所定义的多核苷酸序列和调控序列(例如适宜启动子、增强子、终止子等)，从而容许在宿主细胞或宿主生物体中表达(例如转录和翻译)蛋白质产物。
本发明的载体可呈载体形式，例如质粒、粘粒、YAC、病毒载体或转座子。
在优选但非限制性方面中，本发明的载体包括i)至少一个如上文所述的核酸；其可操作地连结至ii)一或多个调控元件，例如启动子和任选的适宜终止子；以及任选的iii)一或多个基因构建体的其他元件，例如3'-或5'-UTR序列、前导序列、选择标记物、表达标记物/报告基因和/或可促进或增加转化或整合(的效率)的元件。
优选的宿主细胞是大肠杆菌。然而，可使用任何原核或真核表达系统，例如细菌、酵母、丝状真菌、昆虫、植物细胞和哺乳动物细胞。
优选的载体、启动子和宿主细胞皆是能够表达糖基化或非糖基化重组蛋白的载体、启动子和宿主细胞，例如：用于原核表达的pET26a(具有T7启动子)或pTrcHis2(具有trplac启动子)质粒、用于转移的pUC19、pUC 57或pCR4TOPO质粒、以及用于蛋白质表达的大肠杆菌BL21(DE3)或大肠杆菌NiCo21宿主细胞、或仅用于质粒扩增的大肠杆菌Top 10。
疫苗制剂
将融合蛋白与生理上可接受的媒剂一起、任选地与佐剂组合配制于药物组合物中。
由此提供包括融合蛋白或至少两种分别包括至少两个不同抗原性氨基酸序列的融合蛋白的组合与生理上可接受的媒剂的疫苗。
在另一实施方式中，提供包括编码所述融合蛋白的核酸构建体的疫苗组合物。
在一些实施方式中，疫苗可包括一或多种药学上可接受的媒剂或赋形剂。赋形剂包括本身不会诱导产生抗体且不会伤害接受组合物的对象的组分。适宜赋形剂通常是缓慢代谢的大分子，例如糖类、聚乳酸、聚乙醇酸、聚合氨基酸、氨基酸共聚物、蔗糖、海藻糖、乳糖和脂质聚集体(例如油微滴或脂质体)。本领域普通技术人员已熟知适宜的药物媒剂，包括但不限于稀释剂，例如水、生理盐水及其他。适宜地，无菌无热原磷酸盐缓冲生理盐水是药物媒剂。另外，可存在添加剂，例如润湿剂或乳化剂、pH缓冲物质等。
药物组合物、免疫原性组合物或疫苗可进一步包括佐剂。“佐剂”用于增强组合物功效且包括但不限于氢氧化铝(alum)、磷酸铝、水包油或油包水性乳液、Toll样受体激动剂、N-乙酰基-降胞壁酰基-L-丙氨酰基-D-异谷氨酰胺(-MDP)、N-乙酰基-胞壁酰基-L-苏氨酰基-D-异谷氨酰胺(nor-MDP)、PEI、AS01或AS02(GlaxoSmithKline)、GLA-SE(IDRI)和类似制剂；以及本领域已知的类似佐剂。也可使用基于纯化角鲨烯和角鲨烷、经高度纯化的二缩甘露醇单油酸酯乳化的佐剂，包含ISA 51和720。是佐剂的另一实例，其是角鲨烯、聚氧乙烯脱水山梨糖醇单油酸酯(80)和脱水山梨糖醇三油酸酯的水包油性乳液。
将疫苗配制成用于拟施用对象的适宜剂量。所施用剂量可随个体的病状、性别、体重和年龄、施用途径和所用佐剂而变化。可使用诸如悬浮液或液体溶液等剂型的疫苗。可将疫苗与如上文所述的药学上可接受的媒剂一起配制。适宜剂量包括但不限于约0.1微克至约100微克，优选为约1微克至约50微克、仍优选地1微克至20微克、1微克至15微克或甚至1微克至10微克的本文所述的融合蛋白。
疫苗接种
免疫原性组合物或疫苗可以是多组分/多抗原免疫原性组合物或疫苗。
在免疫原性组合物或疫苗旨在用于多施用方案如初免-加强方案的情形下，初免组合物可与加强组合物包括相同或不同组合物。然而，初免-加强方案在本发明背景下并非强制性的。
可通过任何方便途径，优选为肠胃外、经肌内、经真皮内、经皮下、经黏膜或经静脉内施用免疫原性组合物或疫苗。
可利用各种技术来进行DNA疫苗接种，例如电穿孔、无针方式如颗粒轰击和高压递送、真皮贴剂、呈微粒或脂质体形式的DNA疫苗制剂。
本发明描述在对象中产生免疫反应的方法，其包括施用有效量的本发明疫苗的步骤。所述疫苗可预防性施用(即预防感染)或用以提供保护且优选地涉及诱导抗体和/或T细胞免疫性。所述方法可产生一级免疫反应、二级免疫反应、加强反应或免疫反应的组合。
疫苗意欲在任何阶段来保护对象对抗疟疾，包含红细胞前阶段如肝阶段和/或有性或无性血液阶段。
根据本发明，增加了针对疟原虫属抗原的免疫反应的量级和/或记忆。
尤其地，本发明的MSP3融合构建体触发产生抗MSP3嗜细胞抗体，例如IgG1和IgG3抗体。可通过测量所述抗体的效价来测定保护水平。
附图和实施例阐释本发明，而不限制其范围。
实施例：
先前研究已展示，频繁疟疾暴露使得在成人中产生免疫性，其预防或缓解疾病。此免疫性可通过施用来自疟疾免疫成人的免疫球蛋白(IgG)被动转移。
鉴别出寄生虫杀死机制，称为抗体依赖性细胞介导的抑制(ADCI)。通过ADCI筛选宽基因组DNA库导致鉴别出裂殖子-表面蛋白3(MSP3)且随后鉴别出若干其他抗原，包括PEBS。
将嗜细胞抗体鉴别为保护替代物：在许多不同设定下的流行病学研究中发现介导ADCI的嗜细胞(白细胞结合性)抗MSP3抗体IgG1和IgG3始终与疟疾风险的减小有关。所述抗体也在受感染动物中介导针对恶性疟原虫的保护。
所述研究指示有效免疫反应所具有的特性且指导研发改良的疫苗制剂。
基于此，发明者现已展示，与MSP3-LSP(涵盖MSP3-1的186-271区域的长合成肽)相比，在B细胞和T细胞层面上，融合蛋白CRM97-MSP3将免疫原性增加20-100倍。参见实施例1。使用10倍低的免疫化剂量，可由此达成对来自人类、小鼠和松鼠猴的淋巴细胞的免疫原性的重大改良以及抗体持续时间的主要改良。
在红细胞前阶段，先前研究已进一步展示，在黑猩猩中可通过LSA3来诱发针对大规模子孢子攻击的保护效能，所述效能取决于很可能抑制LS产生的IFN-γ和预防子孢子侵袭的抗体。
在实施例2中，发明者已展示，生物融合体CRM-LSA3构建体强烈增加T细胞和B细胞反应。
实施例1和2中所获得的结果已证实可使用来自红细胞阶段的其他抗原如MSP3-2和MSP3-3与CRM的构建体再现(参见实施例3)。
实施例4提供使用LSA5-CRM构建体的结果。
材料和方法
表达构建体的生成和在大肠杆菌中产生生物融合蛋白
以化学方式合成(GenScript)编码由在N-末端和C-末端共价连接至疟疾肽抗原的去毒白喉毒素CRM197构成的嵌合免疫原的基因序列(图1)且对其进行密码子优化以在大肠杆菌中产生。分别在5’和3’末端添加用于Nco I和Xho I的限制位点以克隆于表达质粒pET-26a(Novagen)中。通过测序检查插入穿梭质粒pUC57中的序列且加速冻干(4μg)。
PP21中的MSP3-1肽(plasmodB acc.Nbr PF3D7_1035400)对应于MSP3-1中的氨基酸(AA)155至249。
已针对CRM197设计其他混合免疫原(表3)。在PP22中，MSP3-1肽被MSP3-2肽(MSP3-2的AA 178至257，PlasmodB acc.Nbr PF3D7_1035500)代替。在PP23中，C-末端的MSP3-2肽被MSP3-3肽(MSP3-3中的AA 246至307，PlasmodB acc.Nbr PF3D7_1035600)代替。PP25在两个CRM197末端含有相同LSA3肽(AA 176至325，PlasmodB acc.Nbr PF3D7_0220000)。
表3：免疫原PP21、PP22、PP23、PP25和LSA5-CRM的物理化学特性
*lsp：长合成肽
将大肠杆菌转移菌株Top 10(Invitrogen)[F–mcrAΔ(mrr-hsdRMS-mcrBC)Φ80lacZΔM15ΔlacX74recA1araD139Δ(ara leu)7697galU galK rpsL(StrR)endA1nupG]用于克隆分子程序和质粒增殖。
在菌株BL21(DE3)[F–ompT hsdSB(rB–mB)gal dcm(DE3)](NEB)中表达重组体。
使用Nco I和Xho I消化含有混合序列的穿梭质粒pUC57(Genscript)和表达质粒pET26a。通过在电泳后进行凝胶提取(QIAGEN)来回收插入体和线性化pET26a的带。将凝胶纯化插入体以3的插入体对质粒比率接合于pET26a内部。使用接合反应来转化化学感受态大肠杆菌Top 10且平铺于皮氏培养皿(Petri dish)中含有50μg/mL卡那霉素(kanamycin)的LB琼脂培养基中。
在含有卡那霉素的液体培养基中挑选6个细菌菌落以用于二氧化硅管柱上的质粒小量制备(QIAGEN)。通过使用信息性限制酶进行消化来检查插入体在pET26a中的正确插入(图2)。
选择具有正确限制特征的质粒来转化BL21(DE3)细菌。
针对6个通过上述限制酶消化进行分析的BL21(DE3)克隆来验证具有正确质粒的转化。
小体积细菌培养物中的重组蛋白产生的优化
在爱伦美氏器皿(Erlenmeyer vessel)中以小培养规模(1L)分析诸如重组蛋白产生持续时间、诱导剂(IPTG)浓度和温度等参数。将5mL稳态过夜培养物稀释至1L(1:200)且进一步在30℃下培养至600nm下的光学密度为0,7-0,8。使用两种IPTG诱导剂浓度：0.1mM和1mM在三个温度：22℃、30℃和37℃下分析重组蛋白表达的诱导。在22℃下过夜培养且通过0.1mM IPTG诱导后获得最佳重组体产量。
在通过固定化金属亲和力色谱(IMAC)纯化后获得1mg至2mg重组产物/公升细菌培养物的产量。
PP21的产生和纯化
实施研究实验室规模(1至2公升)的产生以获得足够PP21重组蛋白来实施鼠类和灵长类动物模型中的临床前免疫原性研究。
先前已在小规模培养物中确立用于细菌培养和重组蛋白产生的方案。
在Ni-NTA树脂(QIAGEN)上通过亲和力来纯化C-末端六组氨酸加标签重组蛋白PP21。
探究在天然或变性条件下的两种纯化程序。
实际上，尽管在天然条件中于细菌裂解物不溶性部分中看不到重组蛋白，但也分析变性条件下的纯化以评价PP21的三维结构对组氨酸标签针对Ni-NTA树脂上固定化Ni2+金属的可用性的假定构象效应。
天然条件下的纯化：
-通过离心(4000g，30min，4℃)回收细菌细胞。
-将细菌沉淀物悬浮于5mL裂解缓冲液(50mM NaH2PO4、300mM NaCl、10mM咪唑，pH8.0)/克生物质中。
-将裂解物在冰上与1mg/mL溶菌酶一起摇晃30min。
-使用30sec冷却间隔在150W下通过5次30sec破裂来裂解细菌。
-将裂解物在冰上与5μg/mL DNA酶I和10μg/mL RNA酶A以及完整组蛋白酶抑制剂(Roche)一起摇晃30min。
-通过在10000g、30min和4℃下离心来清洗裂解物。
-经由0,22μm筛过滤裂解物且在4℃下于摆盘上以20mL体积与200μL的Ni NTA树脂一起温育过夜。
-将树脂在40mL体积的裂解缓冲液中深度洗涤5次。将第一步骤上清液(树脂温育后的裂解物)的等分试样保存用于分析。离心步骤在200g下不超过5min。
-通过在500μL含有250mM咪唑的裂解缓冲液中温育树脂5倍来回收重组蛋白。
-汇集洗脱级分且针对pH 7.3PBS经由30kDa筛通过超滤来进行透析。
通过分光光度法在280nM下测量蛋白质浓度且进一步通过如图3中针对PP21所展示的电泳(SDS-PAGE 10％)和免疫印渍进行表征。
变性条件下的纯化：
通过离心(4000g，30min，4℃)回收细菌细胞。
将细菌沉淀物悬浮于5mL变性裂解缓冲液(100mM NaH2PO4、10mM Tris-Cl、8M脲、NaOH pH 8.0)/克生物质中。
将裂解物在冰上摇晃30min。
使用30sec冷却间隔在150W下通过5次30sec破裂来进一步裂解细菌。
通过在10000g、30min和4℃下离心来清洗裂解物。
经由0,22μm筛过滤裂解物且在4℃下于摆盘上以20mL体积与200μL Ni NTA树脂一起温育过夜。
将树脂在40mL体积的变性裂解缓冲液中深度洗涤5次。将第一步骤上清液(树脂温育后的裂解物)的等分试样保存用于分析。离心步骤在200g下不超过5min。
通过在500μL含有250mM咪唑的裂解缓冲液中温育树脂5倍来回收重组蛋白。
汇集洗脱部分且针对pH 7.3PBS经由30kDa筛通过超滤来进行透析。
通过两种方法所达成的纯化产量类似，从而表明亲和力组氨酸标签在天然形式的PP21中具有功能性。
在爱伦美氏器皿中以1公升规模于10个以上产生/纯化试验中可重复获得0,7mg至1mg重组蛋白PP21/公升细菌培养物的产量。
图3展示通过IMAC纯化的重组蛋白PP21。
PP21的温度稳定性
通过蛋白质印记评价的随储存温度而变化的PP21稳定性展示于图4中。在在6℃温度下储存于冰箱中21天时段后没有观察到降解迹象。在室温下，PP21在相同时段下开始展示降解迹象，而其在37℃下于8天后完全降解。然而，此不稳定性不能归因于假定固有分子不稳定性，因为它并非GMP制造产物且它可能含有痕量蛋白酶。
通过pET26a表达于大肠杆菌中的重组蛋白的氨基酸序列展示于下文中。括号中的序列来自表达质粒，粗体的序列来自CRM197白喉毒素。
将C-末端用于通过固定化金属亲和力色谱(IMAC)进行纯化的六组氨酸标签加下划线。
PP21；以斜体加下划线的MSP3-1的序列(PlasmodB ID:PF3D7_1035400)，残基155至249(95aa)
PP22；以斜体加下划线的MSP3-2的序列(PlasmodB ID:PF3D7_1035500)，残基178至257(79aa)
PP23；在CRM197前以斜体加下划线的MSP3-2的序列(PlasmodB ID:PF3D7_1035500)，残基178至257(79aa)，和在CRM197后的斜体的MSP3-3的序列(PlasmodB acc.NbrPF3D7_1035600)，残基246至307(61aa)。
PP25；以斜体加下划线的LSA-3的序列(PlasmodB ID:PF3D7_0220000)，残基176至325(150 aa)
LSA5-CRM蛋白序列(SEQ ID NO:89)
人类免疫原性小鼠模型(HIMM)：所述模型基于在免疫缺陷NOD-SCID-IL-2rγnull(NSG)小鼠中植入人类脾淋巴细胞(Hu-SPL-NSG)，且补充使用常见实验室小鼠如Balb/C和C57BL获得的信息。
Balb/c或C57Bl/6小鼠的免疫化和血液采样
使4至5只Balb/c或C57Bl/6小鼠的组接受2或3次稀释于100μl pH 7.2磷酸盐缓冲盐水(PBS)且乳化于100μl佐剂Montanide ISA 720中的10μg MSP3-1-LSP或1μg PP21的注射。通过皮下注射免疫化且间隔15天重复一次或两次。自第二注射后两周开始通过尾部采血来收集血液且以15天间隔重复直至第一次抗原注射后160天。分离血清且储存于-20℃下直至使用。使同时平行处置的其他组接受1μg或0.2μg PP21。
小鼠血清中的抗MSP3-LSP抗体效价的测定
在小鼠血清中通过酶联免疫吸附分析(ELISA)测定MSP3-LSP特异性抗体效价。使用2μg/ml经PBS稀释的MSP3-1-LSP或MSP3-1-LSP肽a、b、c或d中的一者在4℃下过夜涂覆平底微量滴定板(Nunc-Thermo Scientific,USA)。在洗涤(PBS,pH 7.2)和饱和(PBS,3％非脂乳)后，添加测试血清的连续稀释液(稀释于PBS、3％非脂乳、0.05％Tween20中)且温育1小时。阴性对照由免疫前小鼠血清组成。通过随后添加辣根过氧化物酶偶联的山羊抗小鼠IgG(H+L)(Invitrogen,USA)、一小时之后添加过氧化物酶底物四甲基联苯胺(Amresco,USA)来揭示特异性抗体。特异性抗体效价对应于最后阳性稀释度的倒数。
人类脾捐献和伦理考虑
根据国家器官和组织捐献和移植组织(National Organization for Organ&Tissues Donation&Transplantation(NOOTDT)，Lebanon)的伦理协议从死亡器官移植供体获得人类脾。由患者自己在其生命期间或在死亡后由其父母签署捐献器官以用于移植或科学研究的知情同意。
人类脾细胞制备
如先前所述，在手术切除后24小时内处理人类脾(Brams P,1998)。简言之，解剖脾组织并制备细胞悬浮液。使用格氏溶液(Gey’s solution)将红细胞在25℃下裂解5-10min。在洗涤后，将白细胞再悬浮于由37％胎牛血清(FCS)(Sigma,USA)、10％二甲基亚砜(DMSO)(Sigma,USA)和53％RPMI 1640(Sigma,USA)组成的培养基中，然后冷藏保存于液氮中直至使用。从每一脾供体分离的细胞的平均数量为100±40亿。
人类脾细胞在NSG小鼠中的植入和免疫化
从Jackson实验室(USA)获得NOD.Cg-Prkdcscid-IL2rγtm1WjI/SzJ(NSG)小鼠且饲养于无菌微型隔离器中。在使用的前将所有食物、水、笼和衬垫高压灭菌。将6-至8周龄NSG小鼠包含于实验中。
将人类脾细胞在第0天以4×106个细胞/ml与或不与1μg/ml抗原一起在补充有10％胎牛血清、1％非必需氨基酸(NEAA 100×)、2mM谷氨酰胺、2mM丙酮酸钠和50μg/ml庆大霉素(gentamicin)的RPMI1640培养基(完全培养基)中培养。所有培养试剂皆购自Sigma,USA。在第1天，添加25IU/ml的重组人类IL-2(Gibco Invitrogen)。在第3天，收获脾细胞，洗涤且再悬浮于汉克氏平衡盐溶液(Hank’s Balanced Salt Solution，HBSS)中。使每一NSG小鼠接受30×106个经抗原引发或未引发的脾细胞的腹膜腔内注射(ip)。在第7天和第21天，使用经腹膜腔内(ip)注射的于200μl HBSS-Montanide ISA 720或MF59佐剂(v/v)中的10μg抗原加强重建小鼠(Hu-SPL-NSG)。使用未引发的脾细胞重建的小鼠仅接受佐剂。在每次加强后一周收集血样。
Hu-SPL-NSG小鼠血清中的人类MSP3-1-LSP特异性抗体的测定
通过ELISA实施所述测定。简言之，为检测小鼠血清中的总人类IgG，使用在0.1MpH 9.5碳酸盐缓冲液中的2.5μg/ml经纯化山羊抗人类IgG(H+L)(Invitrogen,USA)在4℃下过夜涂覆平底微量滴定板(Nunc-Thermo Scientific,USA)。在洗涤(PBS,pH 7.2)和饱和(PBS,3％非脂乳)后，添加测试血清(稀释于PBS、3％非脂乳、0.05％Tween20中)且温育1小时。阴性对照由相同动物的免疫前小鼠血清组成。通过随后添加辣根过氧化物酶偶联的山羊抗人类IgG(H+L)(Invitrogen,USA)、一小时之后添加过氧化物酶底物四甲基联苯胺(Amresco,USA)来揭示人类IgG。计算Hu-SPL-NSG小鼠血清中的总人类IgG浓度并与标准人类IgG溶液(Zymed,USA)进行比较。实施相同测试以检测抗原特异性抗体，除了使用在PBS中的2.5μg/ml MSP3-1-LSP涂覆板。在此情形下，阴性对照由从未感染疟原虫属的个体的血清组成，而阳性对照由来自超免疫非洲成人的血清池组成。在两种情形下，测试每一血清的连续稀释液以测定抗体效价。对于特异性抗体效价测定而言，在产生高于截止值(阴性对照OD×2)的吸光度时，测试可视为阳性。使用对人类IgG子类具有特异性的二级小鼠单克隆抗体(分别以最终稀释度1/4,000、1/10,000、1/10,000和1/60,000使用克隆NL16[IgG1；Skybio,UK]、HP6002[IgG2；Sigma-Aldrich,德国]以及Zg4和GB7B[分别是IgG3和IgG4；Skybio,UK))、随后使用以1/4000稀释于PBS中的辣根过氧化物酶偶联的山羊抗小鼠IgG(Invitrogen)来检测IgG子类。
通过实时逆转录PCR(RTqPCR)来量化不同细胞因子、趋化因子和转录因子的基因表达
将经免疫化和未免疫化小鼠的脾细胞以2×106个细胞/ml在完全RPMI1640培养基中在使用免疫化抗原刺激或不刺激下进行培养。在培养24h后使用RNeasy Mini试剂盒(Quiagen,德国)提取总细胞RNA。使用RevertAid M-MuLV酶(RevertAid试剂盒第一链合成试剂盒，Thermo Scientific Fermentas)在20μl反应混合物中实施逆转录。简言之，将1μl寡dT18引物添加至约400ng总RNA中，混合并在65℃下温育5min。将管置于冰上保持数分钟且短暂离心，然后添加如由制造商所推荐的5×反应缓冲液、Ribolock Rnase抑制剂(20u/μl)、dNTP(10mM)和逆转录酶(200u/μl)。将反应混合物在42℃下温育60min。通过在70℃下加热5min来使酶失活。使用定量PCR测量可视为Th1或Treg细胞特性的不同人类细胞因子、趋化因子和转录因子的相对表达。使用如由制造商所推荐的LightCycler 480SYBR GreenMaster,La Roche来实施PCR混合物。于LightCycler 480机器(La Roche)中在95℃下实施PCR扩增5min(1个循环)，随后进行45个循环的95℃、10sec温育和55-57℃、10sec温育。一式三份运行每一试样。用作内部参照物的管家基因是贝塔-肌动蛋白(β-肌动蛋白)和次黄嘌呤磷酸核糖基转移酶1(HPRT1)(geNorm分析)。基于所产生的PCR曲线来计算循环阈值(Ct)。通过2ΔΔCt方法计算相对表达水平。
免疫荧光分析
使用来自主要含有恶性疟原虫(3D7)的成熟裂殖体的红细胞培养物的风干、丙酮固定的薄涂片来进行免疫荧光分析。将稀释于PBS–1％牛血清白蛋白中的Hu-SPL-NSG血清在37℃下于湿润室中温育1h。在使用PBS洗涤后，通过使用在PBS中稀释至1/400的AlexaFluor偶联山羊抗小鼠IgG(Molecular Probes和Invitrogen)利用伊文思蓝复染色(Evansblue counterstain)(1/200)来检测抗体。
结果
实施例1：PP21，即CRMP97-MS3融合构建体的免疫原性
在下列动物模型中评价由PP21诱导的免疫反应：
·BALB-C小鼠
·C57BL小鼠
·松鼠猴
·人类免疫原性小鼠模型(HIMM)，其中在体内对移植到免疫受损NSG小鼠中的来自人类脾组织的细胞进行免疫化且使用来自免疫化动物的血清和细胞用于免疫分析。
所有实验都以对比方式利用临床实验中所使用的基准抗原MSP3-LSP(涵盖MSP3-1的186-271区域的长合成肽)且使用Montanide ISA 720来实施，因为实验室小鼠通常对氢氧化铝反应不良且HIMM中的注射途径不容许使用氢氧化铝，且主要是由于旨在比较构建体而非佐剂，知晓在人类中，呈MSP3LSP形式的氢氧化铝佐剂化CRM(以脑膜炎球菌或肺炎球菌疫苗形式)提供非常好的反应。
然而，也在实验室小鼠中使用氢氧化铝实施成功免疫化，其在Balb/C中即使在两次免疫化后产生＞25600的效价，且在C57bl中产生3200-25600的效价(图19)。
与小鼠中的MSP3-LSP相比，使用本发明的PP21生物融合体MSP3-1构建体可观察到免疫原性的重大改良。
PP21在所使用的所有模型中诱导高于基准抗原MSP3-LSP的靶嗜细胞子类的血清学反应。
1.低剂量极为有效：与其他CRM偶联疫苗相比，获得免疫原性的巨大增加，从而指示融合程序产生与化学偶联同等有效的产物。易于采用显著较低剂量，此使得可比较仅1μgPP21与10μg参考MSP3-LSP(过去，发现10μG与临床中所采用的15μG在实验室小鼠中没有显著不同)。通过不同方式测定所述差异，参见图6至9。使用4个不同批次的PP21在4组Balb/C和C57bl小鼠中可再现结果。使用PP21的其他剂量发现着眼于较低剂量，例如在小鼠和松鼠猴中探究0.2μg相比于1μg。高免疫原性还导致探究与3次相比的仅2次免疫化。
2.ADCI靶的识别的较宽广度：含于疫苗构建体内的肽“b”、“c”和“d”定义由在ADCI中有效的抗体靶向的不同B细胞表位。分别在1μg和10μg下，如图9(右侧图)中所展示，在使用PP21进行疫苗接种的小鼠的血清中与当前的MSP3-1-LSP(左侧图)相比，与这些肽的反应性较高，从而表明在使用PP21时ADCI靶识别的量级和广度较高和较宽。与此发现一致，主要经由肽《b》和《c-d》展现交叉反应的MSP3家族的6个成员的识别模式在使用PP21时较宽。这也意味着，由PP21诱发的抗体将经由与裂殖子表面上的6种而并非仅一种蛋白质的抗体桥触发来触发ADCI。
3.人类淋巴细胞中的极高B细胞反应：更重要的是，如在HIMM模型中所评测，人类B细胞反应展示类似重大改良且免疫原性增加40-100倍。(图10)。在平行实验中，使用PP21以及96个氨基酸的当前MSP3-LSP，使用1μg PP21的抗体效价比使用10μg MSP3-LSP高20至100倍。在3组各5只属于3HLA种类的动物中可再现结果。
4.在使用Montanide ISA720或MF59作为佐剂时，结果也可再现(图14)
5.在体外使用寄生虫组分MSP3-LSP攻击人类淋巴细胞时，获得高IFN-γ分泌(图11)。此重要结果指示，CRM Th表位并不优先于疟原虫属特异性MSR3T细胞表位，且由此在通过寄生虫攻击时可从接种疫苗个体预期T辅助细胞，从而有较大机会在需要时快速产生回忆性抗体。
细胞因子特征的详细分析指示，反应细胞主要是T辅助细胞类型1(图12展示使用CXCL10和Tbet获得的结果的实施例)
6.嗜细胞IgG1的主导性：如使用强Th1反应所预计，同型研究揭示几乎完全由IgG1构成的嗜细胞同型的较大主导性，IgG1也是MSP3-LSP免疫化个体中的主导同型。使用Montanide或MF59作为佐剂时(图15和16)，都是如此。尽管这些结果是在人类模型中所获得，但其很好地预示了可在志愿者中诱发的未来反应。
7.与天然寄生虫蛋白的反应性：在IFAT(图13)和蛋白质印记中，由PP21接种疫苗诱发的抗体与寄生虫天然蛋白反应。不仅与合成抗原，且主要与寄生虫蛋白的抗体反应性是在疟疾攻击期间活化ADCI防御机制和由天然寄生虫攻击适当加强抗体反应的关键特征。
8.极低免疫化剂量是有效的：评价0.2μg和1μg/免疫化且与10μg MSP3-LSP进行比较(图17)。在1μg剂量的PP21下，在第2次免疫化后达到平稳，而在0.2μg剂量下，需要第三次免疫化来达到大致相同的高水平抗体，且一只动物不具有反应。然而，1μg特征指示，2次免疫化可能是足够的，且因此可值得探究。
9.在南美松鼠猴中观察到类似的高免疫原性(图20)：使用1μg和0.2μg由Montanide 720佐剂化的PP21来对通常对免疫化的反应较差的南美灵长类动物免疫化。在1μg下达到接近小鼠中所看到的效价的高反应(参见图18)且在0.2μg下效价低约5倍(未展示)。尽管同一实验中的效价对比尚未由巴西同事实施，但MSP3LSP在用于此模型中时具有极差的免疫原性。
10.免疫反应的持续时间得以显著改良(图8的上图和下图)：长期分析展示基本组分的显著改良；抗体反应的持续时间：在免疫化后随访通过PP21或LSP免疫化的小鼠6个月。效价的衰减是渐进性的，但较为缓慢，从而在6个月时，剩余效价高于使用MSP3-LSP所获得的最大值。使用PP21的持续6个月以上的剩余效价在1/200 000–1/300 000范围内，与之相比，使用当前MSP3-LSP的范围约为1/50 000。
实施例2：PP25，即CRMP97-LSA3融合构建体的免疫原性
LSA3是红细胞前阶段抗原，其具有许多有吸引力的特征，通过经保护对未保护志愿者的差异反应发现，其在株系中较为保守，其在大量动物包含高级灵长类动物和黑猩猩中具有高度抗原性和免疫原性，且随后诱导针对子孢子阶段的人类寄生虫恶性疟原虫的大规模攻击的免疫反应保护。保护与抗原特异性干扰素γ反应有关。将PP25的免疫原性与使用LSA3但并无偶联或任何融合的对照构建体(DG729)进行比较。免疫化和免疫分析的条件与上文使用PP21所述相同。
如针对PP21中的MSP3的情形，使用LSA3-CRM97生物融合体，甚至使用低剂量抗原，观察到抗体反应的类似显著增加。也可看到IFN-γ反应的增加，但显著性较小，因为不含载体的LSA3(DG729)已是IFN-g反应的极良好诱导剂。
在人类免疫原性模型中也证实了balb/C和C57bl小鼠中所记录的增加。
另外，抗LSA3抗体效价与子孢子阶段的恶性疟原虫寄生虫的抑制之间展示极强关联。
参见图21-26中所展示的结果。
实施例3：PP23，即MSP3-2-CRMP97-MSP3-3融合构建体的免疫原性
已证实，使用依赖于MSP3-1与CRM和与LSA3的融合的PP21所获得的结果可使用来自红细胞阶段的其他抗原例如MSP3-2和MSP3-3与CRM的构建体——称为PP23来再现。实际上，通过构建体PP23(MSP3-2-CRMP97-MSP3-3)在HIMM模型中所移植的人类淋巴细胞中诱发强B细胞和T细胞反应(图27)，效价比通过在Montanide中的单独MSP3-2CT免疫化的小鼠平均高10倍。抗体子类主要是IgG1种类，其是能够在ADCI机制中与单核细胞协同作用的主要嗜细胞种类。类似地，诱导强T细胞反应，如通过在体外由MSP3-2或MSP3-3再刺激的PP23免疫化人类淋巴细胞的IFN-γ分泌所测量。
实施例4：LSA5-CRM
肝阶段抗原-5(LSA5)，也称为PEBS(红细胞前和血液阶段抗原)或SR 11.1(11.1恶性疟原虫基因的子区)，在单一分子中组合了MSP3和LSA3的特征。它含有使其不同于大基因(mega-gene)Pf 11.1的其余部分的独特序列，且在株系中完全保守。它由来自经辐射-减毒的子孢子免疫的志愿者的血清识别且因其诱导针对红细胞前和无性血液阶段的保护而较为独特。它表达于红细胞前和血液阶段两者中。通过以下方式来证实LSA5针对红细胞前阶段的保护作用：汇聚性体外侵袭抑制研究，通过被动转移抗LSA5抗体所达成的体内保护，和通过使用重组LSA5接种疫苗来防止攻击的灵长类动物中的概念验证研究。对于血液阶段而言，天然存在的人类和人工诱导的动物抗Pf LSA5抗体发挥出杀死寄生虫的ADCI介导的效应。在来自病区的个体中的抗原性较高，其中IgG3抗体在具有传染免疫即暴露诱导的保护的个体中占主导地位。大量流行病学研究发现与针对临床疟疾攻击的保护的密切关联和经药物治疗的脑疟疾的改良预后。最后，LSA5具有高度免疫原性，从而达成小鼠中的显著较高效价和高于来自MSP3免疫化小鼠的血清的ADCI活性。
将原理类似于前面3个实施例的LSA5与CRM197的生物融合体表达于大肠杆菌中，证实其抗原性且进行初步免疫原性研究。在使用与CRM的融合体时，LSA5免疫原性极高(图28)；在BALb/c小鼠(n＝5)中比较1μg与10μg剂量的生物融合体LSA5-CRM/MontanideISA720的免疫原性。实验条件类似于在图8中使用MSP3所述。在第0、14和28天(箭头)通过生物融合体LSA5-CRM/Montanide ISA720免疫化。利用LSA5-LSP作为抗原，使用在第0、7、21、42天收集的血清通过ELISA滴定来进行血清抗体检测。
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<110> 维克芙奥私人有限公司
<120> 作为抗疟疾疫苗的生物融合蛋白
<130> B2284PC00
<160> 89
<170> PatentIn version 3.5
<210> 1
<211> 1103
<212> PRT
<213> 恶性疟原虫
<400> 1
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Lys Lys Lys Val Lys Val Lys Val Lys Asp Glu Gly Lys Lys Glu Lys
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Asp Glu Glu Phe Phe Lys Thr Phe Val Ser Phe Asn Leu Tyr His Asn
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Asn Asn Glu Lys Asn Ile Ser Tyr Asp Lys Asn Leu Val Lys Gln Glu
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Asn Asp Asn Lys Asp Glu Ala Arg Gly Asn Asp Asn Met Cys Gly Asn
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Tyr Asp Ile His Asn Glu Arg Gly Glu Met Leu Asp Lys Gly Lys Ser
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His Asp Asp Asn Asn Ile Cys Asn Tyr Leu Ser His Asn Glu Gly Glu
370 375 380
Asn Val Ile Glu Arg Glu Asp Lys Leu Phe Asn Lys Leu Asn Asn Lys
385 390 395 400
Asn Tyr Arg Asn Glu Glu Glu Lys Lys Lys Asn Gln Ile Asn Phe Asp
405 410 415
Tyr Leu Lys Lys Lys Ile Lys Asn Asn Gln Asp Val Phe Glu Glu Thr
420 425 430
Ile Gln Lys Cys Phe Leu Ile Asn Leu Lys Lys Thr Leu Asn Leu Ile
435 440 445
Asn Lys Ile Met Tyr Leu Lys Asn Val Glu Phe Arg Lys Tyr Asn Leu
450 455 460
Asp Tyr Ile Arg Lys Ile Asn Tyr Glu Lys Cys Phe Tyr Tyr Lys Asn
465 470 475 480
Tyr Ile Asp Ile Lys Lys Lys Ile Ser Glu Leu Gln Lys Asp Asn Glu
485 490 495
Ser Leu Lys Ile Gln Val Asp Arg Leu Glu Lys Lys Lys Ala Thr Leu
500 505 510
Ile Tyr Lys Leu Asn Asn Asp Asn Ile Arg Lys His Ile Leu Asp Asn
515 520 525
Asn Ile Lys Asp Tyr Gln Asn Gly Ile Asp Asn Ser Lys Val Ser Tyr
530 535 540
Phe Asp Glu Gly Glu Asn Pro Tyr Asn Arg Asn Asn Lys Asn Tyr Arg
545 550 555 560
Thr Asp Asn Lys Asn Ser Asp Asp Asn Asn Asn Asn Asn Asn Tyr Tyr
565 570 575
Tyr Asn Asn Tyr Asn Ser Asp Asp Asn Tyr Asn Ser Glu Asp Asn Glu
580 585 590
Tyr Asn Asn Gly Asn Tyr Arg Phe Arg Asn Asn Tyr Lys Lys Asp Ser
595 600 605
Leu Asn Glu Asp Asp Val Lys Lys Asn Pro Leu Lys Val Cys His Lys
610 615 620
Ile Asn Ser Asp Ser Asn Ile Phe Val Asn Phe Glu Asn Ile Ile Thr
625 630 635 640
Lys Gln Asn Ile Ile His Ser Glu Pro Phe Arg Asn Leu Leu Lys Glu
645 650 655
Ser Asn Glu Leu Tyr Ile Thr Leu Lys Glu Lys Glu Lys Glu Asn Ile
660 665 670
Ile Leu Lys Asn Glu Ile Leu Lys Met Glu Asn Lys Lys Asp Glu Glu
675 680 685
Tyr Glu His Leu Leu Asn Asn Thr Ile Glu Asp Lys Lys Glu Leu Thr
690 695 700
Arg Ser Ile Lys Glu Leu Glu Ile Asn Met Met Thr Cys Asn Met Glu
705 710 715 720
Lys Asp Lys Ile Ser Asn Lys Val Asn Thr Leu Glu Tyr Glu Ile Asn
725 730 735
Val Leu Lys Asn Ile Asp Lys Asn Gln Thr Met Gln Leu Gln Gln Lys
740 745 750
Glu Asn Asp Ile Leu Lys Met Lys Leu Tyr Ile Glu Lys Leu Lys Leu
755 760 765
Ser Glu Lys Asn Leu Lys Asp Lys Ile Ile Leu Leu Glu Asn Glu Lys
770 775 780
Asp Lys Met Leu Ser Gly Ile His Ile Lys Asp Asn Ser Phe Asn Glu
785 790 795 800
Glu Ser Lys Ser Glu Glu Gly Lys Ile Gln Leu Arg Asp Ile Gln Asn
805 810 815
Asp Asn Asp Glu Lys Tyr Asp Asp Glu Lys Lys Arg Phe Lys Glu Leu
820 825 830
Phe Ile Glu Asn Gln Lys Leu Lys Glu Glu Leu Asn Lys Lys Arg Asn
835 840 845
Val Glu Glu Glu Leu His Ser Leu Arg Lys Asn Tyr Asn Ile Ile Asn
850 855 860
Glu Glu Ile Glu Glu Ile Thr Lys Glu Phe Glu Lys Lys Gln Glu Gln
865 870 875 880
Val Asp Glu Met Ile Leu Gln Ile Lys Asn Lys Glu Leu Glu Leu Leu
885 890 895
Asp Lys Phe Asn Asn Lys Met Asn Lys Ala Tyr Val Glu Glu Lys Leu
900 905 910
Lys Glu Leu Lys Asn Thr Tyr Glu Glu Lys Met Lys His Ile Asn Asn
915 920 925
Ile Tyr Lys Lys His Asp Asp Phe Val Asn Ile Tyr Leu Asn Leu Phe
930 935 940
Phe Gln Ala Arg Lys Asn Ala Ile Leu Ser Asp Ser Gln Arg Glu Glu
945 950 955 960
Gln Met Asn Leu Phe Ile Lys Leu Lys Asp Lys Tyr Asp Ile Ile Phe
965 970 975
Gln Lys Lys Ile Glu Leu Thr Asp Ile Leu Lys Asn Val Tyr Asp Cys
980 985 990
Asn Lys Lys Leu Ile Gly His Cys Gln Asp Leu Glu Lys Glu Asn Ser
995 1000 1005
Thr Leu Gln Asn Lys Leu Ser Asn Glu Ile Lys Asn Ser Lys Met
1010 1015 1020
Leu Ser Lys Asn Leu Ser Lys Asn Ser Asp Asp His Leu Leu Ile
1025 1030 1035
Glu Glu Asn Asn Glu Leu Arg Arg Arg Leu Ile Cys Ser Val Cys
1040 1045 1050
Met Glu Asn Phe Arg Asn Tyr Ile Ile Ile Lys Cys Gly His Ile
1055 1060 1065
Tyr Cys Asn Asn Cys Ile Phe Asn Asn Leu Lys Thr Arg Asn Arg
1070 1075 1080
Lys Cys Pro Gln Cys Lys Val Pro Phe Asp Lys Lys Asp Leu Gln
1085 1090 1095
Lys Ile Phe Leu Asp
1100
<210> 2
<211> 104
<212> PRT
<213> 恶性疟原虫
<400> 2
His Asn Asn Asn Glu Lys Asn Ile Ser Tyr Asp Lys Asn Leu Val Lys
1 5 10 15
Gln Glu Asn Asp Asn Lys Asp Glu Ala Arg Gly Asn Asp Asn Met Cys
20 25 30
Gly Asn Tyr Asp Ile His Asn Glu Arg Gly Glu Met Leu Asp Lys Gly
35 40 45
Lys Ser Tyr Ser Gly Asp Glu Lys Ile Asn Thr Ser Asp Asn Ala Lys
50 55 60
Ser Cys Ser Gly Asp Glu Lys Val Ile Thr Ser Asp Asn Gly Lys Ser
65 70 75 80
Tyr Asp Tyr Val Lys Asn Glu Ser Glu Glu Gln Glu Glu Lys Glu Asn
85 90 95
Met Leu Asn Asn Lys Lys Arg Ser
100
<210> 3
<211> 27
<212> PRT
<213> 恶性疟原虫
<400> 3
Lys Lys Arg Asn Val Glu Glu Glu Leu His Ser Leu Arg Lys Asn Tyr
1 5 10 15
Asn Ile Ile Asn Glu Glu Ile Glu Glu Ile Thr
20 25
<210> 4
<211> 80
<212> PRT
<213> 恶性疟原虫
<400> 4
Asn Glu Glu Glu Ile Thr Thr Lys Gly Ala Ser Ala Gln Ser Gly Ala
1 5 10 15
Ser Ala Gln Ser Gly Ala Ser Ala Gln Ser Gly Ala Ser Ala Gln Ser
20 25 30
Gly Ala Ser Ala Gln Ser Gly Ala Ser Ala Gln Ser Gly Thr Ser Gly
35 40 45
Pro Ser Gly Pro Ser Gly Thr Ser Pro Ser Ser Arg Ser Asn Thr Leu
50 55 60
Pro Arg Ser Asn Thr Ser Ser Gly Ala Ser Pro Pro Ala Asp Ala Ser
65 70 75 80
<210> 5
<211> 390
<212> PRT
<213> 恶性疟原虫
<400> 5
Met Ala His His His His His His Pro Gly Gly Ser Gly Ser Gly Thr
1 5 10 15
Met Ala Ile Ser Val Thr Met Asp Asn Ile Leu Ser Gly Phe Glu Asn
20 25 30
Glu Tyr Asp Val Ile Tyr Leu Lys Pro Leu Ala Gly Val Tyr Arg Ser
35 40 45
Leu Lys Lys Gln Ile Glu Lys Asn Ile Phe Thr Phe Asn Leu Asn Leu
50 55 60
Asn Asp Ile Leu Asn Ser Arg Leu Lys Lys Arg Lys Tyr Phe Leu Asp
65 70 75 80
Val Leu Glu Ser Asp Leu Met Gln Phe Lys His Ile Ser Ser Asn Glu
85 90 95
Tyr Ile Ile Glu Asp Ser Phe Lys Leu Leu Asn Ser Glu Gln Lys Asn
100 105 110
Thr Leu Leu Lys Ser Tyr Lys Tyr Ile Lys Glu Ser Val Glu Asn Asp
115 120 125
Ile Lys Phe Ala Gln Glu Gly Ile Ser Tyr Tyr Glu Lys Val Leu Ala
130 135 140
Lys Tyr Lys Asp Asp Leu Glu Ser Ile Lys Lys Val Ile Lys Glu Glu
145 150 155 160
Lys Glu Lys Phe Pro Ser Ser Pro Pro Thr Thr Pro Pro Ser Pro Ala
165 170 175
Lys Thr Asp Glu Gln Lys Lys Glu Ser Lys Phe Leu Pro Phe Leu Thr
180 185 190
Asn Ile Glu Thr Leu Tyr Asn Asn Leu Val Asn Lys Ile Asp Asp Tyr
195 200 205
Leu Ile Asn Leu Lys Ala Lys Ile Asn Asp Cys Asn Val Glu Lys Asp
210 215 220
Glu Ala His Val Lys Ile Thr Lys Leu Ser Asp Leu Lys Ala Ile Asp
225 230 235 240
Asp Lys Ile Asp Leu Phe Lys Asn Pro Thr Asp Phe Glu Ala Ile Lys
245 250 255
Lys Leu Ile Asn Asp Asp Thr Lys Lys Asp Met Leu Gly Lys Leu Leu
260 265 270
Ser Thr Gly Leu Val Gln Asn Phe Pro Asn Thr Ile Ile Ser Lys Leu
275 280 285
Ile Glu Gly Lys Phe Gln Asp Met Leu Asn Ile Ser Gln His Gln Cys
290 295 300
Val Lys Lys Gln Cys Pro Glu Asn Ser Gly Cys Phe Arg His Leu Asp
305 310 315 320
Glu Arg Glu Glu Cys Lys Cys Leu Leu Asn Tyr Lys Gln Glu Gly Asp
325 330 335
Lys Cys Val Glu Asn Pro Asn Pro Thr Cys Asn Glu Asn Asn Gly Gly
340 345 350
Cys Asp Ala Asp Ala Thr Cys Thr Glu Glu Asp Ser Gly Ser Ser Arg
355 360 365
Lys Lys Ile Thr Cys Glu Cys Thr Lys Pro Asp Ser Tyr Pro Leu Phe
370 375 380
Asp Gly Ile Phe Cys Ser
385 390
<210> 6
<211> 272
<212> PRT
<213> 恶性疟原虫
<400> 6
Met Lys Val Ile Lys Thr Leu Ser Ile Ile Asn Phe Phe Ile Phe Val
1 5 10 15
Thr Phe Asn Ile Lys Asn Glu Ser Lys Tyr Ser Asn Thr Phe Ile Asn
20 25 30
Asn Ala Tyr Asn Met Ser Ile Arg Arg Ser Met Ala Glu Ser Lys Pro
35 40 45
Ser Thr Gly Ala Gly Gly Ser Ala Gly Gly Ser Ala Gly Gly Ser Ala
50 55 60
Gly Gly Ser Ala Gly Gly Ser Ala Gly Gly Ser Ala Gly Ser Gly Asp
65 70 75 80
Gly Asn Gly Ala Asp Ala Glu Gly Ser Ser Ser Thr Pro Ala Thr Thr
85 90 95
Thr Thr Thr Lys Thr Thr Thr Thr Thr Thr Thr Thr Asn Asp Ala Glu
100 105 110
Ala Ser Thr Ser Thr Ser Ser Glu Asn Pro Asn His Lys Asn Ala Glu
115 120 125
Thr Asn Pro Lys Gly Lys Gly Glu Val Gln Glu Pro Asn Gln Ala Asn
130 135 140
Lys Glu Thr Gln Asn Asn Ser Asn Val Gln Gln Asp Ser Gln Thr Lys
145 150 155 160
Ser Asn Val Pro Pro Thr Gln Asp Ala Asp Thr Lys Ser Pro Thr Ala
165 170 175
Gln Pro Glu Gln Ala Glu Asn Ser Ala Pro Thr Ala Glu Gln Thr Glu
180 185 190
Ser Pro Glu Leu Gln Ser Ala Pro Glu Asn Lys Gly Thr Gly Gln His
195 200 205
Gly His Met His Gly Ser Arg Asn Asn His Pro Gln Asn Thr Ser Asp
210 215 220
Ser Gln Lys Glu Cys Thr Asp Gly Asn Lys Glu Asn Cys Gly Ala Ala
225 230 235 240
Thr Ser Leu Leu Asn Asn Ser Ser Asn Ile Ala Ser Ile Asn Lys Phe
245 250 255
Val Val Leu Ile Ser Ala Thr Leu Val Leu Ser Phe Ala Ile Phe Ile
260 265 270
<210> 7
<211> 354
<212> PRT
<213> 恶性疟原虫
<400> 7
Met Lys Ser Phe Ile Asn Ile Thr Leu Ser Leu Phe Leu Leu His Leu
1 5 10 15
Tyr Ile Tyr Ile Asn Asn Val Ala Ser Lys Glu Ile Val Lys Lys Tyr
20 25 30
Asn Leu Asn Leu Arg Asn Ala Ile Leu Asn Asn Asn Ser Gln Ile Glu
35 40 45
Asn Glu Glu Asn Val Asn Thr Thr Ile Thr Gly Asn Asp Phe Ser Gly
50 55 60
Gly Glu Phe Leu Trp Pro Gly Tyr Thr Glu Glu Leu Lys Ala Lys Lys
65 70 75 80
Ala Ser Glu Asp Ala Glu Lys Ala Ala Asn Asp Ala Glu Asn Ala Ser
85 90 95
Lys Glu Ala Glu Glu Ala Ala Lys Glu Ala Val Asn Leu Lys Glu Ser
100 105 110
Asp Lys Ser Tyr Thr Lys Ala Lys Glu Ala Cys Thr Ala Ala Ser Lys
115 120 125
Ala Lys Lys Ala Val Glu Thr Ala Leu Lys Ala Lys Asp Asp Ala Glu
130 135 140
Lys Ser Ser Lys Ala Asp Ser Ile Ser Thr Lys Thr Lys Glu Tyr Ala
145 150 155 160
Glu Lys Ala Lys Asn Ala Tyr Glu Lys Ala Lys Asn Ala Tyr Gln Lys
165 170 175
Ala Asn Gln Ala Val Leu Lys Ala Lys Glu Ala Ser Ser Tyr Asp Tyr
180 185 190
Ile Leu Gly Trp Glu Phe Gly Gly Gly Val Pro Glu His Lys Lys Glu
195 200 205
Glu Asn Met Leu Ser His Leu Tyr Val Ser Ser Lys Asp Lys Glu Asn
210 215 220
Ile Ser Lys Glu Asn Asp Asp Val Leu Asp Glu Lys Glu Glu Glu Ala
225 230 235 240
Glu Glu Thr Glu Glu Glu Glu Leu Glu Glu Lys Asn Glu Glu Glu Thr
245 250 255
Glu Ser Glu Ile Ser Glu Asp Glu Glu Glu Glu Glu Glu Glu Glu Glu
260 265 270
Lys Glu Glu Glu Asn Asp Lys Lys Lys Glu Gln Glu Lys Glu Gln Ser
275 280 285
Asn Glu Asn Asn Asp Gln Lys Lys Asp Met Glu Ala Gln Asn Leu Ile
290 295 300
Ser Lys Asn Gln Asn Asn Asn Glu Lys Asn Val Lys Glu Ala Ala Glu
305 310 315 320
Ser Ile Met Lys Thr Leu Ala Gly Leu Ile Lys Gly Asn Asn Gln Ile
325 330 335
Asp Ser Thr Leu Lys Asp Leu Val Glu Glu Leu Ser Lys Tyr Phe Lys
340 345 350
Asn His
<210> 8
<211> 188
<212> PRT
<213> 恶性疟原虫
<400> 8
Tyr Glu Lys Ala Lys Asn Ala Tyr Gln Lys Ala Asn Gln Ala Val Leu
1 5 10 15
Lys Ala Lys Glu Ala Ser Ser Tyr Asp Tyr Ile Leu Gly Trp Glu Phe
20 25 30
Gly Gly Gly Val Pro Glu His Lys Lys Glu Glu Asn Met Leu Ser His
35 40 45
Leu Tyr Val Ser Ser Lys Asp Lys Glu Asn Ile Ser Lys Glu Asn Asp
50 55 60
Asp Val Leu Asp Glu Lys Glu Glu Glu Ala Glu Glu Thr Glu Glu Glu
65 70 75 80
Glu Leu Glu Glu Lys Asn Glu Glu Glu Thr Glu Ser Glu Ile Ser Glu
85 90 95
Asp Glu Glu Glu Glu Glu Glu Glu Glu Glu Lys Glu Glu Glu Asn Asp
100 105 110
Lys Lys Lys Glu Gln Glu Lys Glu Gln Ser Asn Glu Asn Asn Asp Gln
115 120 125
Lys Lys Asp Met Glu Ala Gln Asn Leu Ile Ser Lys Asn Gln Asn Asn
130 135 140
Asn Glu Lys Asn Val Lys Glu Ala Ala Glu Ser Ile Met Lys Thr Leu
145 150 155 160
Ala Gly Leu Ile Lys Gly Asn Asn Gln Ile Asp Ser Thr Leu Lys Asp
165 170 175
Leu Val Glu Glu Leu Ser Lys Tyr Phe Lys Asn His
180 185
<210> 9
<211> 25
<212> PRT
<213> 恶性疟原虫
<400> 9
Tyr Glu Lys Ala Lys Asn Ala Tyr Gln Lys Ala Asn Gln Ala Val Leu
1 5 10 15
Lys Ala Lys Glu Ala Ser Ser Tyr Asp
20 25
<210> 10
<211> 27
<212> PRT
<213> 恶性疟原虫
<400> 10
Ala Lys Glu Ala Ser Ser Tyr Asp Tyr Ile Leu Gly Trp Glu Phe Gly
1 5 10 15
Gly Gly Val Pro Glu His Lys Lys Glu Glu Asn
20 25
<210> 11
<211> 28
<212> PRT
<213> 恶性疟原虫
<400> 11
Pro Glu His Lys Lys Glu Glu Asn Met Leu Ser His Leu Tyr Val Ser
1 5 10 15
Ser Lys Asp Lys Glu Asn Ile Ser Lys Glu Asn Asp
20 25
<210> 12
<211> 41
<212> PRT
<213> 恶性疟原虫
<400> 12
Met Leu Ser His Leu Tyr Val Ser Ser Lys Asp Lys Glu Asn Ile Ser
1 5 10 15
Lys Glu Asn Asp Asp Val Leu Asp Glu Lys Glu Glu Glu Ala Glu Glu
20 25 30
Thr Glu Glu Glu Glu Leu Glu Glu Lys
35 40
<210> 13
<211> 34
<212> PRT
<213> 恶性疟原虫
<400> 13
Glu Glu Glu Asn Asp Lys Lys Lys Glu Gln Glu Lys Glu Gln Ser Asn
1 5 10 15
Glu Asn Asn Asp Gln Lys Lys Asp Met Glu Ala Gln Asn Leu Ile Ser
20 25 30
Lys Asn
<210> 14
<211> 53
<212> PRT
<213> 恶性疟原虫
<400> 14
Asn Leu Ile Ser Lys Asn Gln Asn Asn Asn Glu Lys Asn Val Lys Glu
1 5 10 15
Ala Ala Glu Ser Ile Met Lys Thr Leu Ala Gly Leu Ile Lys Gly Asn
20 25 30
Asn Gln Ile Asp Ser Thr Leu Lys Asp Leu Val Glu Glu Leu Ser Lys
35 40 45
Tyr Phe Lys Asn His
50
<210> 15
<211> 371
<212> PRT
<213> 恶性疟原虫
<400> 15
Met Asn Lys Ile Tyr Asn Ile Thr Phe Leu Phe Ile Leu Leu Asn Leu
1 5 10 15
Tyr Ile Asn Glu Asn Asn Phe Ile Arg Asn Glu Leu Ile Asn Glu Lys
20 25 30
Asn His Asn Leu Arg Asn Gly Ser Met Tyr Asn Asn Asp Lys Ile Leu
35 40 45
Ser Lys Asn Glu Val Asp Thr Asn Ile Glu Ser Asn Glu Asn Ser Ile
50 55 60
His Glu Ser Gly His Lys Ile Asp Gly Glu Glu Val Leu Lys Ala Asn
65 70 75 80
Val Asp Asp Ile Thr Tyr Lys Lys Lys Asn Val Asp Asp Ser Glu Ile
85 90 95
Pro Phe Ser Gly Tyr Asp Ile Gln Ala Thr Tyr Gln Phe Pro Ser Thr
100 105 110
Ser Gly Gly Asn Asn Val Ile Pro Leu Pro Ile Lys Gln Ser Gly Glu
115 120 125
Asn Gln Tyr Thr Val Thr Ser Ile Ser Gly Ile Gln Lys Gly Ala Asn
130 135 140
Gly Leu Thr Gly Ala Thr Glu Asn Ile Thr Gln Val Val Gln Ala Asn
145 150 155 160
Ser Glu Thr Asn Lys Asn Pro Thr Ser His Ser Asn Ser Thr Thr Thr
165 170 175
Ser Leu Asn Asn Asn Ile Leu Gly Trp Glu Phe Gly Gly Gly Ala Pro
180 185 190
Gln Asn Gly Ala Ala Glu Asp Lys Lys Thr Glu Tyr Leu Leu Glu Gln
195 200 205
Ile Lys Ile Pro Ser Trp Asp Arg Asn Asn Ile Pro Asp Glu Asn Glu
210 215 220
Gln Val Ile Glu Asp Pro Gln Glu Asp Asn Lys Asp Glu Asp Glu Asp
225 230 235 240
Glu Glu Thr Glu Thr Glu Asn Leu Glu Thr Glu Asp Asp Asn Asn Glu
245 250 255
Glu Ile Glu Glu Asn Glu Glu Asp Asp Ile Asp Glu Glu Ser Val Glu
260 265 270
Glu Lys Glu Glu Glu Glu Glu Lys Lys Glu Glu Glu Glu Lys Lys Glu
275 280 285
Glu Lys Lys Glu Glu Lys Lys Pro Asp Asn Glu Ile Thr Asn Glu Val
290 295 300
Lys Glu Glu Gln Lys Tyr Ser Ser Pro Ser Asp Ile Asn Ala Gln Asn
305 310 315 320
Leu Ile Ser Asn Lys Asn Lys Lys Asn Asp Glu Thr Lys Lys Thr Ala
325 330 335
Glu Asn Ile Val Lys Thr Leu Val Gly Leu Phe Asn Glu Lys Asn Glu
340 345 350
Ile Asp Ser Thr Ile Asn Asn Leu Val Gln Glu Met Ile His Leu Phe
355 360 365
Ser Asn Asn
370
<210> 16
<211> 211
<212> PRT
<213> 恶性疟原虫
<400> 16
Ser Glu Thr Asn Lys Asn Pro Thr Ser His Ser Asn Ser Thr Thr Thr
1 5 10 15
Ser Leu Asn Asn Asn Ile Leu Gly Trp Glu Phe Gly Gly Gly Ala Pro
20 25 30
Gln Asn Gly Ala Ala Glu Asp Lys Lys Thr Glu Tyr Leu Leu Glu Gln
35 40 45
Ile Lys Ile Pro Ser Trp Asp Arg Asn Asn Ile Pro Asp Glu Asn Glu
50 55 60
Gln Val Ile Glu Asp Pro Gln Glu Asp Asn Lys Asp Glu Asp Glu Asp
65 70 75 80
Glu Glu Thr Glu Thr Glu Asn Leu Glu Thr Glu Asp Asp Asn Asn Glu
85 90 95
Glu Ile Glu Glu Asn Glu Glu Asp Asp Ile Asp Glu Glu Ser Val Glu
100 105 110
Glu Lys Glu Glu Glu Glu Glu Lys Lys Glu Glu Glu Glu Lys Lys Glu
115 120 125
Glu Lys Lys Glu Glu Lys Lys Pro Asp Asn Glu Ile Thr Asn Glu Val
130 135 140
Lys Glu Glu Gln Lys Tyr Ser Ser Pro Ser Asp Ile Asn Ala Gln Asn
145 150 155 160
Leu Ile Ser Asn Lys Asn Lys Lys Asn Asp Glu Thr Lys Lys Thr Ala
165 170 175
Glu Asn Ile Val Lys Thr Leu Val Gly Leu Phe Asn Glu Lys Asn Glu
180 185 190
Ile Asp Ser Thr Ile Asn Asn Leu Val Gln Glu Met Ile His Leu Phe
195 200 205
Ser Asn Asn
210
<210> 17
<211> 21
<212> PRT
<213> 恶性疟原虫
<400> 17
Ser Glu Thr Asn Lys Asn Pro Thr Ser His Ser Asn Ser Thr Thr Thr
1 5 10 15
Ser Leu Asn Asn Asn
20
<210> 18
<211> 27
<212> PRT
<213> 恶性疟原虫
<400> 18
Leu Asn Asn Asn Ile Leu Gly Trp Glu Phe Gly Gly Gly Ala Pro Gln
1 5 10 15
Asn Gly Ala Ala Glu Asp Lys Lys Thr Glu Tyr
20 25
<210> 19
<211> 33
<212> PRT
<213> 恶性疟原虫
<400> 19
Pro Gln Asn Gly Ala Ala Glu Asp Lys Lys Thr Glu Tyr Leu Leu Glu
1 5 10 15
Gln Ile Lys Ile Pro Ser Trp Asp Arg Asn Asn Ile Pro Asp Glu Asn
20 25 30
Glu
<210> 20
<211> 53
<212> PRT
<213> 恶性疟原虫
<400> 20
Leu Leu Glu Gln Ile Lys Ile Pro Ser Trp Asp Arg Asn Asn Ile Pro
1 5 10 15
Asp Glu Asn Glu Gln Val Ile Glu Asp Pro Gln Glu Asp Asn Lys Asp
20 25 30
Glu Asp Glu Asp Glu Glu Thr Glu Thr Glu Asn Leu Glu Thr Glu Asp
35 40 45
Asp Asn Asn Glu Glu
50
<210> 21
<211> 42
<212> PRT
<213> 恶性疟原虫
<400> 21
Glu Glu Glu Lys Lys Glu Glu Lys Lys Glu Glu Lys Lys Pro Asp Asn
1 5 10 15
Glu Ile Thr Asn Glu Val Lys Glu Glu Gln Lys Tyr Ser Ser Pro Ser
20 25 30
Asp Ile Asn Ala Gln Asn Leu Ile Ser Asn
35 40
<210> 22
<211> 52
<212> PRT
<213> 恶性疟原虫
<400> 22
Asn Leu Ile Ser Asn Lys Asn Lys Lys Asn Asp Glu Thr Lys Lys Thr
1 5 10 15
Ala Glu Asn Ile Val Lys Thr Leu Val Gly Leu Phe Asn Glu Lys Asn
20 25 30
Glu Ile Asp Ser Thr Ile Asn Asn Leu Val Gln Glu Met Ile His Leu
35 40 45
Phe Ser Asn Asn
50
<210> 23
<211> 424
<212> PRT
<213> 恶性疟原虫
<400> 23
Met Lys Lys Ile Val Asn Ile Ile Phe Tyr Ile Leu Tyr Leu Tyr Ile
1 5 10 15
Tyr Lys Arg Asn Leu Val Gln Asn Glu Asn Val Asn Lys Ser Asn Leu
20 25 30
Arg Lys Gly Leu Ser Thr Asn Asn Ser Glu Asn Gly Ile Lys Ser Leu
35 40 45
Lys Asp Glu Asp Glu His Ile Asn Ile Ile Gly Asp Asp Phe Ser Ala
50 55 60
Phe Ser Tyr Gly Gly Tyr Pro Ile Tyr Glu Thr Thr Gly Ser Leu Gly
65 70 75 80
Thr Gly Val Glu Ser Val Lys Ala Ile Asp Gly Glu Ser Gly Thr Ser
85 90 95
Met Asp Ser Lys Pro Lys Glu Asn Lys Ile Ser Thr Glu Pro Gly Ala
100 105 110
Asp Gln Val Ser Ile Gly Leu Val Asn Glu Ser Asp Ser Ser Leu Glu
115 120 125
Asn Asp Lys Lys Lys Lys Glu Asn Val Lys Lys Glu Met Leu Gly Thr
130 135 140
Glu Lys Glu Gly Ser Pro Asp Ser His Asp Ser Ser Lys Glu Lys Leu
145 150 155 160
Asn Leu Asn Asp Asn Ser Lys Trp Ser Asp Phe Leu Lys Asn Ile Val
165 170 175
Thr Phe Gly Gly Phe Gly Pro Thr Val Val His Asp Val Ser Asp Thr
180 185 190
Leu Ser Asp Ile Ser Lys Asp Glu Val Thr Gln Lys Thr Thr Lys Asp
195 200 205
Ile Gly Ser Thr Leu Leu Asp Phe Phe Leu Pro Leu Pro Thr Lys Asn
210 215 220
Thr Asn Thr Tyr Glu Lys Lys Asn Glu Asn Lys Asn Val Ser Asn Val
225 230 235 240
Asp Ser Lys Thr Lys Ser Asn Glu Lys Gly Arg Pro Pro Thr Tyr Ser
245 250 255
Pro Ile Leu Asp Asp Gly Ile Glu Phe Ser Gly Gly Leu Tyr Phe Asn
260 265 270
Glu Lys Lys Ser Thr Glu Glu Asn Lys Gln Lys Asn Val Leu Glu Ser
275 280 285
Val Asn Leu Thr Ser Trp Asp Lys Glu Asp Ile Val Lys Glu Asn Glu
290 295 300
Asp Val Lys Asp Glu Lys Asp Glu Asp Asp Glu Glu Glu Glu Glu Lys
305 310 315 320
Tyr Glu Asn Glu Ile Ile Lys Gln Pro Glu Asp Ile Leu Asp Glu Glu
325 330 335
Glu Val Leu Glu Glu Glu Ile Leu Glu Glu Asn Lys Asn Asp Thr Val
340 345 350
Asp Thr Ser Asp Leu Glu Lys Lys Asn Ile Pro Asp Leu Ser Asn Asp
355 360 365
Asn Asn Tyr Tyr Ser Leu Ile Tyr Lys Asn Tyr Lys Asp Asn Asp Lys
370 375 380
Ser Glu Lys Thr Ala Gln Thr Leu Ile Thr Ala Leu Ile Ser Leu Leu
385 390 395 400
Asn Gly Lys Asn Glu Leu Asp Ala Thr Ile Arg Arg Leu Lys His Arg
405 410 415
Phe Met Glu Phe Phe Thr Tyr Asn
420
<210> 24
<211> 197
<212> PRT
<213> 恶性疟原虫
<400> 24
Tyr Glu Lys Lys Asn Glu Asn Lys Asn Val Ser Asn Val Asp Ser Lys
1 5 10 15
Thr Lys Ser Asn Glu Lys Gly Arg Pro Pro Thr Tyr Ser Pro Ile Leu
20 25 30
Asp Asp Gly Ile Glu Phe Ser Gly Gly Leu Tyr Phe Asn Glu Lys Lys
35 40 45
Ser Thr Glu Glu Asn Lys Gln Lys Asn Val Leu Glu Ser Val Asn Leu
50 55 60
Thr Ser Trp Asp Lys Glu Asp Ile Val Lys Glu Asn Glu Asp Val Lys
65 70 75 80
Asp Glu Lys Asp Glu Asp Asp Glu Glu Glu Glu Glu Lys Tyr Glu Asn
85 90 95
Glu Ile Ile Lys Gln Pro Glu Asp Ile Leu Asp Glu Glu Glu Val Leu
100 105 110
Glu Glu Glu Ile Leu Glu Glu Asn Lys Asn Asp Thr Val Asp Thr Ser
115 120 125
Asp Leu Glu Lys Lys Asn Ile Pro Asp Leu Ser Asn Asp Asn Asn Tyr
130 135 140
Tyr Ser Leu Ile Tyr Lys Asn Tyr Lys Asp Asn Asp Lys Ser Glu Lys
145 150 155 160
Thr Ala Gln Thr Leu Ile Thr Ala Leu Ile Ser Leu Leu Asn Gly Lys
165 170 175
Asn Glu Leu Asp Ala Thr Ile Arg Arg Leu Lys His Arg Phe Met Glu
180 185 190
Phe Phe Thr Tyr Asn
195
<210> 25
<211> 24
<212> PRT
<213> 恶性疟原虫
<400> 25
Tyr Glu Lys Lys Asn Glu Asn Lys Asn Val Ser Asn Val Asp Ser Lys
1 5 10 15
Thr Lys Ser Asn Glu Lys Gly Arg
20
<210> 26
<211> 26
<212> PRT
<213> 恶性疟原虫
<400> 26
Ser Asn Glu Lys Gly Arg Pro Pro Thr Tyr Ser Pro Ile Leu Asp Asp
1 5 10 15
Gly Ile Glu Phe Ser Gly Gly Leu Tyr Phe
20 25
<210> 27
<211> 29
<212> PRT
<213> 恶性疟原虫
<400> 27
Gly Ile Glu Phe Ser Gly Gly Leu Tyr Phe Asn Glu Lys Lys Ser Thr
1 5 10 15
Glu Glu Asn Lys Gln Lys Asn Val Leu Glu Ser Val Asn
20 25
<210> 28
<211> 32
<212> PRT
<213> 恶性疟原虫
<400> 28
Ser Thr Glu Glu Asn Lys Gln Lys Asn Val Leu Glu Ser Val Asn Leu
1 5 10 15
Thr Ser Trp Asp Lys Glu Asp Ile Val Lys Glu Asn Glu Asp Val Lys
20 25 30
<210> 29
<211> 33
<212> PRT
<213> 恶性疟原虫
<400> 29
Asp Thr Ser Asp Leu Glu Lys Lys Asn Ile Pro Asp Leu Ser Asn Asp
1 5 10 15
Asn Asn Tyr Tyr Ser Leu Ile Tyr Lys Asn Tyr Lys Asp Asn Asp Lys
20 25 30
Ser
<210> 30
<211> 52
<212> PRT
<213> 恶性疟原虫
<400> 30
Ser Leu Ile Tyr Lys Asn Tyr Lys Asp Asn Asp Lys Ser Glu Lys Thr
1 5 10 15
Ala Gln Thr Leu Ile Thr Ala Leu Ile Ser Leu Leu Asn Gly Lys Asn
20 25 30
Glu Leu Asp Ala Thr Ile Arg Arg Leu Lys His Arg Phe Met Glu Phe
35 40 45
Phe Thr Tyr Asn
50
<210> 31
<211> 697
<212> PRT
<213> 恶性疟原虫
<400> 31
Met Lys Lys Ile Tyr Ser Ile Phe Phe Ser Leu Phe Ile Leu Asn Leu
1 5 10 15
His Ile Tyr Ile Lys Asn Ile Lys Cys Asn Asp Leu Ile Asn Tyr Asn
20 25 30
Asp Ser Asn Leu Arg Asn Gly Leu Leu Asn Asn Ser Leu Asp Leu Thr
35 40 45
Asn Gly Leu Asn Asn Lys Asp Asn Ser Phe Ile Asp Ser Lys Ile Glu
50 55 60
Glu His Glu Asn Lys Ser Tyr Gln Asn Lys Asp Asn Asn Ile Ser Ile
65 70 75 80
Val Gly Gln Asp Val Pro Ile Thr Ser Val Tyr Ser Ser Lys Ile Ile
85 90 95
Asn Ala Asn Asp Leu Glu Gly Asn Ser Ile Asp Asp Thr Lys Gly Leu
100 105 110
Ser Val Thr Asn Ser Gly Phe Asp Asp Gly Ser Ala Phe Gly Gly Gly
115 120 125
Leu Pro Phe Ser Gly Tyr Ser Pro Leu Gln Gly Asn His Asn Lys Cys
130 135 140
Pro Asp Glu Asn Phe Cys Lys Gly Ile Lys Asn Val Leu Ser Cys Pro
145 150 155 160
Pro Lys Asn Ser Thr Gly Arg Asn Gly Asp Trp Ile Ser Val Ala Val
165 170 175
Lys Glu Ser Ser Thr Thr Asn Lys Gly Val Leu Val Pro Pro Arg Arg
180 185 190
Thr Lys Leu Cys Leu Arg Asn Ile Asn Lys Val Trp His Arg Ile Lys
195 200 205
Asp Glu Lys Asn Phe Lys Glu Glu Phe Val Lys Val Ala Leu Gly Glu
210 215 220
Ser Asn Ala Leu Met Lys His Tyr Lys Glu Lys Asn Leu Asn Ala Leu
225 230 235 240
Thr Ala Ile Lys Tyr Gly Phe Ser Asp Met Gly Asp Ile Ile Lys Gly
245 250 255
Thr Asp Leu Ile Asp Tyr Gln Ile Thr Lys Asn Ile Asn Arg Ala Leu
260 265 270
Asp Lys Ile Leu Arg Asn Glu Thr Ser Asn Asp Lys Ile Lys Lys Arg
275 280 285
Val Asp Trp Trp Glu Ala Asn Lys Ser Ala Phe Trp Asp Ala Phe Met
290 295 300
Cys Gly Tyr Lys Val His Ile Gly Asn Lys Pro Cys Pro Glu His Asp
305 310 315 320
Asn Met Asp Arg Ile Pro Gln Tyr Leu Arg Trp Phe Arg Glu Trp Gly
325 330 335
Thr Tyr Val Cys Ser Glu Tyr Lys Asn Lys Phe Glu Asp Val Ile Lys
340 345 350
Leu Cys Asn Ile Gln Gln Phe Thr Asn Gln Asp Asp Ser Gln Leu Leu
355 360 365
Glu Ile Ser Lys Lys Asp Lys Cys Lys Glu Ala Leu Lys His Tyr Glu
370 375 380
Glu Trp Val Asn Arg Arg Arg Pro Glu Trp Lys Gly Gln Cys Asp Lys
385 390 395 400
Phe Glu Lys Glu Lys Ser Lys Tyr Glu Asp Thr Lys Ser Ile Thr Ala
405 410 415
Glu Lys Tyr Leu Lys Glu Ile Cys Ser Glu Cys Asp Cys Lys Tyr Lys
420 425 430
Asp Leu Asp Asn Thr Phe Lys Glu Phe Lys Asp Asn Val Thr Leu Leu
435 440 445
Lys Ala Val Ile Asp Asn Lys Lys Asn Gln Asp Ser Leu Thr Thr Thr
450 455 460
Ser Leu Ser Thr Ser Ile Asn Ser Val Arg Asp Ser Ser Asn Leu Asp
465 470 475 480
Gln Arg Gly Asn Ile Thr Thr Ser Gln Gly Asn Ser His Arg Ala Thr
485 490 495
Val Val Gln Gln Val Asp Gln Thr Asn Arg Leu Asp Asn Val Asn Ser
500 505 510
Val Thr Gln Arg Gly Asn Asn Asn Tyr Asn Asn Asn Leu Glu Arg Gly
515 520 525
Leu Gly Ser Gly Ala Leu Pro Gly Thr Asn Ile Ile Thr Glu Glu Lys
530 535 540
Tyr Ser Leu Glu Leu Ile Lys Leu Thr Ser Lys Asp Glu Glu Asp Ile
545 550 555 560
Ile Lys His Asn Glu Asp Val Arg Glu Glu Ile Glu Glu Gln Gln Glu
565 570 575
Asp Ile Glu Glu Asp Glu Glu Glu Leu Glu Asn Glu Gly Glu Glu Thr
580 585 590
Lys Glu Glu Asp Asp Glu Glu Lys Asn Glu Thr Asn Asp Thr Glu Asp
595 600 605
Thr Asp Asp Thr Glu Asp Thr Glu Asp Ile Glu Glu Glu Asn Lys Glu
610 615 620
Lys Glu Leu Ser Asn Gln Gln Gln Ser Glu Lys Lys Ser Ile Ser Lys
625 630 635 640
Val Asp Glu Asp Ser Tyr Arg Ile Leu Ser Val Ser Tyr Lys Asp Asn
645 650 655
Asn Glu Val Lys Asn Val Ala Glu Ser Ile Val Lys Lys Leu Phe Ser
660 665 670
Leu Phe Asn Asp Asn Asn Asn Leu Glu Thr Ile Phe Lys Gly Leu Thr
675 680 685
Glu Asp Met Thr Asp Leu Phe Gln Lys
690 695
<210> 32
<211> 190
<212> PRT
<213> 恶性疟原虫
<400> 32
Asp Asn Val Asn Ser Val Thr Gln Arg Gly Asn Asn Asn Tyr Asn Asn
1 5 10 15
Asn Leu Glu Arg Gly Leu Gly Ser Gly Ala Leu Pro Gly Thr Asn Ile
20 25 30
Ile Thr Glu Glu Lys Tyr Ser Leu Glu Leu Ile Lys Leu Thr Ser Lys
35 40 45
Asp Glu Glu Asp Ile Ile Lys His Asn Glu Asp Val Arg Glu Glu Ile
50 55 60
Glu Glu Gln Gln Glu Asp Ile Glu Glu Asp Glu Glu Glu Leu Glu Asn
65 70 75 80
Glu Gly Glu Glu Thr Lys Glu Glu Asp Asp Glu Glu Lys Asn Glu Thr
85 90 95
Asn Asp Thr Glu Asp Thr Asp Asp Thr Glu Asp Thr Glu Asp Ile Glu
100 105 110
Glu Glu Asn Lys Glu Lys Glu Leu Ser Asn Gln Gln Gln Ser Glu Lys
115 120 125
Lys Ser Ile Ser Lys Val Asp Glu Asp Ser Tyr Arg Ile Leu Ser Val
130 135 140
Ser Tyr Lys Asp Asn Asn Glu Val Lys Asn Val Ala Glu Ser Ile Val
145 150 155 160
Lys Lys Leu Phe Ser Leu Phe Asn Asp Asn Asn Asn Leu Glu Thr Ile
165 170 175
Phe Lys Gly Leu Thr Glu Asp Met Thr Asp Leu Phe Gln Lys
180 185 190
<210> 33
<211> 25
<212> PRT
<213> 恶性疟原虫
<400> 33
Asp Asn Val Asn Ser Val Thr Gln Arg Gly Asn Asn Asn Tyr Asn Asn
1 5 10 15
Asn Leu Glu Arg Gly Leu Gly Ser Gly
20 25
<210> 34
<211> 27
<212> PRT
<213> 恶性疟原虫
<400> 34
Leu Glu Arg Gly Leu Gly Ser Gly Ala Leu Pro Gly Thr Asn Ile Ile
1 5 10 15
Thr Glu Glu Lys Tyr Ser Leu Glu Leu Ile Lys
20 25
<210> 35
<211> 28
<212> PRT
<213> 恶性疟原虫
<400> 35
Lys Tyr Ser Leu Glu Leu Ile Lys Leu Thr Ser Lys Asp Glu Glu Asp
1 5 10 15
Ile Ile Lys His Asn Glu Asp Val Arg Glu Glu Ile
20 25
<210> 36
<211> 28
<212> PRT
<213> 恶性疟原虫
<400> 36
Leu Thr Ser Lys Asp Glu Glu Asp Ile Ile Lys His Asn Glu Asp Val
1 5 10 15
Arg Glu Glu Ile Glu Glu Gln Gln Glu Asp Ile Glu
20 25
<210> 37
<211> 34
<212> PRT
<213> 恶性疟原虫
<400> 37
Glu Glu Asn Lys Glu Lys Glu Leu Ser Asn Gln Gln Gln Ser Glu Lys
1 5 10 15
Lys Ser Ile Ser Lys Val Asp Glu Asp Ser Tyr Arg Ile Leu Ser Val
20 25 30
Ser Tyr
<210> 38
<211> 51
<212> PRT
<213> 恶性疟原虫
<400> 38
Arg Ile Leu Ser Val Ser Tyr Lys Asp Asn Asn Glu Val Lys Asn Val
1 5 10 15
Ala Glu Ser Ile Val Lys Lys Leu Phe Ser Leu Phe Asn Asp Asn Asn
20 25 30
Asn Leu Glu Thr Ile Phe Lys Gly Leu Thr Glu Asp Met Thr Asp Leu
35 40 45
Phe Gln Lys
50
<210> 39
<211> 405
<212> PRT
<213> 恶性疟原虫
<400> 39
Met Asn Lys Phe Leu Asn Ile Ile Phe Tyr Ile Phe Leu Ile Leu Asn
1 5 10 15
Phe Ser Phe Phe Gln Ser Asn Ala Thr Ser Lys Glu Ile Gln Lys Asp
20 25 30
Glu Gln Lys Asn Leu Arg Asn Gly Ser Ser Ile Asn Asn Asn Lys Asn
35 40 45
Ile Glu Asn Lys Asn Asp Asn Ile Glu Thr Gln Tyr Glu Ala Ser Glu
50 55 60
Tyr Ile Glu Lys Gln Asn Asp Ile Leu Asn Met Tyr Asn Asp Glu Lys
65 70 75 80
Glu Lys Asn Asn Asn Asn Ser Leu Asp Thr Asn Val Thr Lys Asn Thr
85 90 95
Val Ile Asp Asn Ser Asn Lys Phe Gln Ser Ile Glu Asp Asn Asn Val
100 105 110
Tyr Asn Lys Gly Ile Phe Val Gly Thr Gly Ile Lys Leu Asn Asp Ser
115 120 125
Gln Thr Thr Ser Asp Asn Tyr Lys Asn Glu Arg Tyr Gln Ile Asp Asp
130 135 140
Glu Lys Leu Lys Tyr Gly Gly Ser Phe Asp Thr Ile Phe Ser Gly Phe
145 150 155 160
Val Asn Leu Leu Thr Pro Ser Ser Pro Thr Gln Asn Asp Gly Ser Thr
165 170 175
Gly Arg Asn Val Pro Pro Pro Ser Glu Pro Asn Val Asp Thr Pro Asp
180 185 190
Pro Pro Thr Ala Pro Ala Pro Val Lys Val Pro Glu Asp Ala Lys Leu
195 200 205
Ser Ser Ser Pro Arg Pro Glu Gly Pro Arg Ala Asn Asn Arg Asn Glu
210 215 220
Asn Asn Gln Asn Thr Asp Pro Tyr Asn His Tyr Phe Ala Trp Glu Ile
225 230 235 240
Gly Gly Gly Ala Pro Thr Tyr Lys Pro Glu Asn Asn Lys Asn Asp Asn
245 250 255
Ile Leu Leu Glu His Val Lys Ile Thr Ser Trp Asp Lys Glu Asp Ile
260 265 270
Ile Lys Glu Asn Glu Asp Thr Lys Arg Glu Val Gln Glu Thr Glu Asp
275 280 285
Thr Asp Glu Thr Glu Asp Thr Asp Glu Thr Glu Glu Thr Glu Asp Met
290 295 300
Glu Asp Glu Asn Glu Ile Val Glu Asp Gln Leu Gln Glu Asn Glu Asp
305 310 315 320
Asp Glu Asp Asn Val Asn Leu Glu Asp Ile Asn Lys Asn Thr Arg Asn
325 330 335
Asp Ile Phe Glu Glu Gln Ile Lys Leu Asp Ser Thr Gln Asp Asp Lys
340 345 350
Ala Gln Lys Leu Ile Ser Asn Glu Tyr Lys Lys Thr Glu Glu Lys Lys
355 360 365
Ser Leu Glu Asp His Val Asn Leu Leu Phe Asn Phe Leu Gln Thr Asn
370 375 380
Asn Gln Leu Asp Pro Ser Leu Lys Asp Leu Glu Asn Glu Leu Thr Phe
385 390 395 400
Phe Leu Asn Asn Tyr
405
<210> 40
<211> 192
<212> PRT
<213> 恶性疟原虫
<400> 40
Pro Glu Gly Pro Arg Ala Asn Asn Arg Asn Glu Asn Asn Gln Asn Thr
1 5 10 15
Asp Pro Tyr Asn His Tyr Phe Ala Trp Glu Ile Gly Gly Gly Ala Pro
20 25 30
Thr Tyr Lys Pro Glu Asn Asn Lys Asn Asp Asn Ile Leu Leu Glu His
35 40 45
Val Lys Ile Thr Ser Trp Asp Lys Glu Asp Ile Ile Lys Glu Asn Glu
50 55 60
Asp Thr Lys Arg Glu Val Gln Glu Thr Glu Asp Thr Asp Glu Thr Glu
65 70 75 80
Asp Thr Asp Glu Thr Glu Glu Thr Glu Asp Met Glu Asp Glu Asn Glu
85 90 95
Ile Val Glu Asp Gln Leu Gln Glu Asn Glu Asp Asp Glu Asp Asn Val
100 105 110
Asn Leu Glu Asp Ile Asn Lys Asn Thr Arg Asn Asp Ile Phe Glu Glu
115 120 125
Gln Ile Lys Leu Asp Ser Thr Gln Asp Asp Lys Ala Gln Lys Leu Ile
130 135 140
Ser Asn Glu Tyr Lys Lys Thr Glu Glu Lys Lys Ser Leu Glu Asp His
145 150 155 160
Val Asn Leu Leu Phe Asn Phe Leu Gln Thr Asn Asn Gln Leu Asp Pro
165 170 175
Ser Leu Lys Asp Leu Glu Asn Glu Leu Thr Phe Phe Leu Asn Asn Tyr
180 185 190
<210> 41
<211> 26
<212> PRT
<213> 恶性疟原虫
<400> 41
Pro Glu Gly Pro Arg Ala Asn Asn Arg Asn Glu Asn Asn Gln Asn Thr
1 5 10 15
Asp Pro Tyr Asn His Tyr Phe Ala Trp Glu
20 25
<210> 42
<211> 22
<212> PRT
<213> 恶性疟原虫
<400> 42
Tyr Asn His Tyr Phe Ala Trp Glu Ile Gly Gly Gly Ala Pro Thr Tyr
1 5 10 15
Lys Pro Glu Asn Asn Lys
20
<210> 43
<211> 27
<212> PRT
<213> 恶性疟原虫
<400> 43
Pro Thr Tyr Lys Pro Glu Asn Asn Lys Asn Asp Asn Ile Leu Leu Glu
1 5 10 15
His Val Lys Ile Thr Ser Trp Asp Lys Glu Asp
20 25
<210> 44
<211> 29
<212> PRT
<213> 恶性疟原虫
<400> 44
Ile Leu Leu Glu His Val Lys Ile Thr Ser Trp Asp Lys Glu Asp Ile
1 5 10 15
Ile Lys Glu Asn Glu Asp Thr Lys Arg Glu Val Gln Glu
20 25
<210> 45
<211> 35
<212> PRT
<213> 恶性疟原虫
<400> 45
Val Asn Leu Glu Asp Ile Asn Lys Asn Thr Arg Asn Asp Ile Phe Glu
1 5 10 15
Glu Gln Ile Lys Leu Asp Ser Thr Gln Asp Asp Lys Ala Gln Lys Leu
20 25 30
Ile Ser Asn
35
<210> 46
<211> 52
<212> PRT
<213> 恶性疟原虫
<400> 46
Gln Lys Leu Ile Ser Asn Glu Tyr Lys Lys Thr Glu Glu Lys Lys Ser
1 5 10 15
Leu Glu Asp His Val Asn Leu Leu Phe Asn Phe Leu Gln Thr Asn Asn
20 25 30
Gln Leu Asp Pro Ser Leu Lys Asp Leu Glu Asn Glu Leu Thr Phe Phe
35 40 45
Leu Asn Asn Tyr
50
<210> 47
<211> 762
<212> PRT
<213> 恶性疟原虫
<400> 47
Met Ile Tyr Ile Leu Ser Ile Val Phe Tyr Ile Phe Phe Leu His Ile
1 5 10 15
Asp Ile Tyr Val Asn Ile Tyr Ser Thr Cys Phe Val Val Asn Glu Gly
20 25 30
Asn Pro Asn Leu Arg Asn Asn Ile Ile Asn Asp Asp Glu Leu Lys Gly
35 40 45
Lys Ala Tyr Asn Asn Thr Ile Asp Ala Asn Asn Gln Asn Ile Glu Tyr
50 55 60
Asn Lys Asn Leu Lys His Asn Val Asn Ser Ser His Ile Ser Lys Phe
65 70 75 80
Ser Asp Ile Met Asp Gln Glu Asp Lys Gly Asp Asn Glu Asn Ser His
85 90 95
Asp Ile Lys Phe Glu Glu Lys Lys Asn Ile Asn Lys Ser Leu Asp Ala
100 105 110
Glu Ser Asn Tyr Gly Ile Asn Glu Ile Ser Ile Thr Gly Asn Asp Ser
115 120 125
Asn Ser Asp Asn Ser Asn Gln Asn Ile Phe Pro Asp Gly Ser Glu Leu
130 135 140
Ala Gly Gly Ile Pro Arg Ser Ile Tyr Thr Ile Asn Leu Gly Phe Asn
145 150 155 160
Lys Cys Pro Thr Glu Glu Ile Cys Lys Asp Phe Ser Asn Leu Pro Gln
165 170 175
Cys Arg Lys Asn Val His Glu Arg Asn Asn Trp Leu Gly Ser Ser Val
180 185 190
Lys Asn Phe Ser Ser Asp Asn Lys Gly Val Leu Val Pro Pro Arg Arg
195 200 205
Gln Ser Leu Cys Leu Arg Ile Thr Leu Gln Asp Phe Arg Thr Lys Lys
210 215 220
Lys Lys Glu Gly Asp Phe Glu Lys Phe Ile Tyr Ser Tyr Ala Ser Ser
225 230 235 240
Glu Ala Arg Lys Leu Arg Thr Ile His Asn Asn Asn Leu Glu Lys Ala
245 250 255
His Gln Ala Ile Arg Tyr Ser Phe Ala Asp Ile Gly Asn Ile Ile Arg
260 265 270
Gly Asp Asp Met Met Asp Thr Pro Thr Ser Lys Glu Thr Ile Thr Tyr
275 280 285
Leu Glu Lys Val Leu Lys Ile Tyr Asn Glu Asn Asn Asp Lys Pro Lys
290 295 300
Asp Ala Lys Lys Trp Trp Thr Glu Asn Arg His His Val Trp Glu Ala
305 310 315 320
Met Met Cys Gly Tyr Gln Ser Ala Gln Lys Asp Asn Gln Cys Thr Gly
325 330 335
Tyr Gly Asn Ile Asp Asp Ile Pro Gln Phe Leu Arg Trp Phe Arg Glu
340 345 350
Trp Gly Thr Tyr Val Cys Glu Glu Ser Glu Lys Asn Met Asn Thr Leu
355 360 365
Lys Ala Val Cys Phe Pro Lys Gln Pro Arg Thr Glu Ala Asn Pro Ala
370 375 380
Leu Thr Val His Glu Asn Glu Met Cys Ser Ser Thr Leu Lys Lys Tyr
385 390 395 400
Glu Glu Trp Tyr Asn Lys Arg Lys Thr Glu Trp Thr Glu Gln Ser Ile
405 410 415
Lys Tyr Asn Asn Asp Lys Ile Asn Tyr Thr Asp Ile Lys Thr Leu Ser
420 425 430
Pro Ser Glu Tyr Leu Ile Glu Lys Cys Pro Glu Cys Lys Cys Thr Lys
435 440 445
Lys Asn Leu Gln Asp Val Phe Glu Leu Thr Phe Asp Gly Lys Ala Leu
450 455 460
Leu Glu Lys Leu Lys Lys Glu Glu Ser Pro Val Ser Asn Ser Val Asn
465 470 475 480
Ala Leu Pro Glu Pro Gly Gln Ile Thr Leu Pro Asp Pro Ser Leu Lys
485 490 495
Gln Thr Thr Gln Gln Glu Asn Gln Pro Val Val Glu Thr Pro Val Thr
500 505 510
Thr Ala Val Ile Asn Glu His Gln Gly Gln Thr Glu Pro Asn Lys Gly
515 520 525
Asp Asn Asn Asn Glu Arg Glu Asn His Glu Ser Asn Val Gly Ser Ile
530 535 540
Gln Glu Val Asn Gln Gly Ser Val Ser Glu Glu Ser His Ser Lys Thr
545 550 555 560
Ile Asp Pro Ser Lys Ile Asp Asp Arg Leu Glu Leu Ser Ser Gly Ser
565 570 575
Ser Ser Leu Glu Gln His Ser Lys Glu Asp Val Lys Lys Gly Cys Ala
580 585 590
Leu Glu Leu Val Pro Leu Ser Leu Ser Asp Ile Glu Gln Ile Ala Asn
595 600 605
Glu Ser Glu Asp Val Leu Glu Glu Ile Glu Glu Glu Ile Asn Thr Asp
610 615 620
Gly Glu Ile Glu Tyr Ile Thr Glu Glu Glu Ile Lys Glu Asp Ile Glu
625 630 635 640
Glu Glu Thr Glu Glu Asp Ile Glu Glu Glu Thr Glu Glu Glu Thr Glu
645 650 655
Glu Glu Thr Glu Glu Glu Ala Asp Glu Glu Thr Val Lys Glu Ile Glu
660 665 670
Asp Lys Pro Glu Gln Glu Ile Lys Asn Lys Ser Leu Glu Glu Lys Gln
675 680 685
Ile Asp Lys Asn Thr Asp Thr Ser Glu Lys Lys Gly Phe Asn Asn Ser
690 695 700
Glu Lys Asp Glu Lys Ala Arg Asn Leu Ile Ser Lys Asn Tyr Lys Asn
705 710 715 720
Tyr Asn Glu Leu Asp Lys Asn Val His Thr Leu Val Asn Ser Ile Ile
725 730 735
Ser Leu Leu Glu Glu Gly Asn Gly Ser Asp Ser Thr Leu Asn Ser Leu
740 745 750
Ser Lys Asp Ile Thr Asn Leu Phe Lys Asn
755 760
<210> 48
<211> 226
<212> PRT
<213> 恶性疟原虫
<400> 48
His Glu Ser Asn Val Gly Ser Ile Gln Glu Val Asn Gln Gly Ser Val
1 5 10 15
Ser Glu Glu Ser His Ser Lys Thr Ile Asp Pro Ser Lys Ile Asp Asp
20 25 30
Arg Leu Glu Leu Ser Ser Gly Ser Ser Ser Leu Glu Gln His Ser Lys
35 40 45
Glu Asp Val Lys Lys Gly Cys Ala Leu Glu Leu Val Pro Leu Ser Leu
50 55 60
Ser Asp Ile Glu Gln Ile Ala Asn Glu Ser Glu Asp Val Leu Glu Glu
65 70 75 80
Ile Glu Glu Glu Ile Asn Thr Asp Gly Glu Ile Glu Tyr Ile Thr Glu
85 90 95
Glu Glu Ile Lys Glu Asp Ile Glu Glu Glu Thr Glu Glu Asp Ile Glu
100 105 110
Glu Glu Thr Glu Glu Glu Thr Glu Glu Glu Thr Glu Glu Glu Ala Asp
115 120 125
Glu Glu Thr Val Lys Glu Ile Glu Asp Lys Pro Glu Gln Glu Ile Lys
130 135 140
Asn Lys Ser Leu Glu Glu Lys Gln Ile Asp Lys Asn Thr Asp Thr Ser
145 150 155 160
Glu Lys Lys Gly Phe Asn Asn Ser Glu Lys Asp Glu Lys Ala Arg Asn
165 170 175
Leu Ile Ser Lys Asn Tyr Lys Asn Tyr Asn Glu Leu Asp Lys Asn Val
180 185 190
His Thr Leu Val Asn Ser Ile Ile Ser Leu Leu Glu Glu Gly Asn Gly
195 200 205
Ser Asp Ser Thr Leu Asn Ser Leu Ser Lys Asp Ile Thr Asn Leu Phe
210 215 220
Lys Asn
225
<210> 49
<211> 33
<212> PRT
<213> 恶性疟原虫
<400> 49
His Glu Ser Asn Val Gly Ser Ile Gln Glu Val Asn Gln Gly Ser Val
1 5 10 15
Ser Glu Glu Ser His Ser Lys Thr Ile Asp Pro Ser Lys Ile Asp Asp
20 25 30
Arg
<210> 50
<211> 29
<212> PRT
<213> 恶性疟原虫
<400> 50
Ser Lys Thr Ile Asp Pro Ser Lys Ile Asp Asp Arg Leu Glu Leu Ser
1 5 10 15
Ser Gly Ser Ser Ser Leu Glu Gln His Ser Lys Glu Asp
20 25
<210> 51
<211> 29
<212> PRT
<213> 恶性疟原虫
<400> 51
Glu Gln His Ser Lys Glu Asp Val Lys Lys Gly Cys Ala Leu Glu Leu
1 5 10 15
Val Pro Leu Ser Leu Ser Asp Ile Glu Gln Ile Ala Asn
20 25
<210> 52
<211> 33
<212> PRT
<213> 恶性疟原虫
<400> 52
Ala Leu Glu Leu Val Pro Leu Ser Leu Ser Asp Ile Glu Gln Ile Ala
1 5 10 15
Asn Glu Ser Glu Asp Val Leu Glu Glu Ile Glu Glu Glu Ile Asn Thr
20 25 30
Asp
<210> 53
<211> 41
<212> PRT
<213> 恶性疟原虫
<400> 53
Glu Ile Glu Asp Lys Pro Glu Gln Glu Ile Lys Asn Lys Ser Leu Glu
1 5 10 15
Glu Lys Gln Ile Asp Lys Asn Thr Asp Thr Ser Glu Lys Lys Gly Phe
20 25 30
Asn Asn Ser Glu Lys Asp Glu Lys Ala
35 40
<210> 54
<211> 61
<212> PRT
<213> 恶性疟原虫
<400> 54
Asn Asn Ser Glu Lys Asp Glu Lys Ala Arg Asn Leu Ile Ser Lys Asn
1 5 10 15
Tyr Lys Asn Tyr Asn Glu Leu Asp Lys Asn Val His Thr Leu Val Asn
20 25 30
Ser Ile Ile Ser Leu Leu Glu Glu Gly Asn Gly Ser Asp Ser Thr Leu
35 40 45
Asn Ser Leu Ser Lys Asp Ile Thr Asn Leu Phe Lys Asn
50 55 60
<210> 55
<211> 272
<212> PRT
<213> 恶性疟原虫
<400> 55
Met Trp Ile Val Lys Phe Leu Ile Val Val His Phe Phe Ile Ile Cys
1 5 10 15
Thr Ile Asn Phe Asp Lys Leu Tyr Ile Ser Tyr Ser Tyr Asn Ile Val
20 25 30
Pro Glu Asn Gly Arg Met Leu Asn Met Arg Ile Leu Gly Glu Glu Lys
35 40 45
Pro Asn Val Asp Gly Val Ser Thr Ser Asn Thr Pro Gly Gly Asn Glu
50 55 60
Ser Ser Ser Ala Ser Pro Asn Leu Ser Asp Ala Ala Glu Lys Lys Asp
65 70 75 80
Glu Lys Glu Ala Ser Glu Gln Gly Glu Glu Ser His Lys Lys Glu Asn
85 90 95
Ser Gln Glu Ser Ala Asn Gly Lys Asp Asp Val Lys Glu Glu Lys Lys
100 105 110
Thr Asn Glu Lys Lys Asp Asp Gly Lys Thr Asp Lys Val Gln Glu Lys
115 120 125
Val Leu Glu Lys Ser Pro Lys Glu Ser Gln Met Val Asp Asp Lys Lys
130 135 140
Lys Thr Glu Ala Ile Pro Lys Lys Val Val Gln Pro Ser Ser Ser Asn
145 150 155 160
Ser Gly Gly His Val Gly Glu Glu Glu Asp His Asn Glu Gly Glu Gly
165 170 175
Glu His Glu Glu Glu Glu Glu His Glu Glu Asp Asp Asp Asp Glu Asp
180 185 190
Asp Asp Thr Tyr Asn Lys Asp Asp Leu Glu Asp Glu Asp Leu Cys Lys
195 200 205
His Asn Asn Gly Gly Cys Gly Asp Asp Lys Leu Cys Glu Tyr Val Gly
210 215 220
Asn Arg Arg Val Lys Cys Lys Cys Lys Glu Gly Tyr Lys Leu Glu Gly
225 230 235 240
Ile Glu Cys Val Glu Leu Leu Ser Leu Ala Ser Ser Ser Leu Asn Leu
245 250 255
Ile Phe Asn Ser Phe Ile Thr Ile Phe Val Val Ile Leu Leu Ile Asn
260 265 270
<210> 56
<211> 9563
<212> PRT
<213> 恶性疟原虫
<400> 56
Met Lys Lys Glu Ser Tyr Arg Phe Leu Asn Ile Ser Ile Asn Asn Gly
1 5 10 15
Ser Asp Lys Lys Lys Lys Ser Asn Phe Phe Val Lys Ile Lys Asn Gly
20 25 30
Thr Asp Leu Lys Asp Thr Lys Lys Asp Arg Ile Arg Phe His Phe Tyr
35 40 45
Phe Tyr Phe Phe Ile Val Lys Ile Ile Leu Leu Ser Leu Leu Ile Trp
50 55 60
Thr Val Ile Tyr Ser Asn Asn Cys Ser Asn Gly Lys Tyr Lys Ser Thr
65 70 75 80
Leu Tyr Ile Val Gly Asn His Leu Arg Phe Arg Gly Phe Arg Ile Leu
85 90 95
Ala Glu Asn Glu Tyr Glu Met Lys Thr Lys Tyr Lys Thr Leu Met Val
100 105 110
Asn Ile Asp Asp Asn Asp Leu Gly Lys Arg Gly Asn Lys Ile Lys Pro
115 120 125
Lys His Lys Lys Val Glu Ile Asn Leu Asn Asp Asn Asn Leu Ser Asn
130 135 140
Asn Glu Ser Lys Arg Lys Ser Arg Arg Lys Lys Val Lys Val Asn Leu
145 150 155 160
Lys Asp Asn Leu Ala Lys Arg Glu Gly Lys Met Lys Arg Arg Asn Lys
165 170 175
Lys Glu Lys Arg Arg Lys Glu Lys Asp Asn Lys Lys Met Asn Glu Leu
180 185 190
Lys Leu Lys Arg Glu Tyr Lys Glu Ser Tyr Leu Leu Asp Asn Lys Ser
195 200 205
Asp Met Asp Val Ile Arg Asn Asp Lys Phe Ser Tyr Phe Thr Leu Tyr
210 215 220
Lys Asn Asn Leu Phe Pro Asn Ser Asn Asn Tyr Phe Leu His Met Leu
225 230 235 240
Lys Thr Tyr Asp Glu Glu Asn Lys Gly Ile Asp Glu Asn Thr Asp Ile
245 250 255
Asn Glu Asn Val Glu Glu Asn Glu Tyr Val Asp Lys Asn Thr Glu Gly
260 265 270
Asp Lys Asp Gly Asp Glu Asp Lys Gly Gly Gly Glu Ser Glu Gly Gly
275 280 285
Asp Gly His Gly Ser Ala Gly Asp Ser Ala Gly Gly Asp Arg Gly Gly
290 295 300
Asp Glu Asn Lys Asp Lys Asp Asn Glu Glu Asn Lys Asp Lys Lys Gly
305 310 315 320
Asn Lys Asp Asp Asp Asp Glu Glu Glu Glu Glu Glu Glu Glu Asp Asp
325 330 335
Glu Glu Lys Glu Glu Lys Asp Glu Lys Asp Glu Lys Asp Glu Lys Asp
340 345 350
Glu Lys Asp Glu Lys Asp Glu Lys Asp Glu Lys Asp Glu Lys Asp Glu
355 360 365
Lys Asp Glu Lys Asp Glu Lys Asp Glu Lys Asp Glu Lys Gly Glu Lys
370 375 380
Asp Glu Ser Lys Gly Glu Glu Lys Phe Leu Lys Glu Glu Lys Met Pro
385 390 395 400
Lys Lys Glu Glu Asn Met Gln Asp Lys Ile Glu Arg Asp Lys Glu Phe
405 410 415
Glu Gly Phe Lys Asp Glu Tyr Phe Thr Gln Met Glu Gly Gly Ala Tyr
420 425 430
Gly Ile Thr Val Glu His Glu Gly Gln Lys Leu Arg Glu Thr Leu Thr
435 440 445
Glu Gly Val Glu Gly Tyr Glu Lys Val Ile Glu Glu Met Glu Gln Thr
450 455 460
Lys Leu Asp Glu Phe Leu Leu Pro Thr Asn Glu Gly Lys Ser Asp Asp
465 470 475 480
Phe Val Ser Glu Met Glu Glu Glu Arg Leu Phe Asn Phe Val Ser Tyr
485 490 495
Met Glu Glu Glu Val Lys Asp Lys Met Phe Ile Glu Arg Glu Gln Gly
500 505 510
Thr Glu Glu Glu Val Ile His Glu Asp Leu Ser Asp Glu Lys Ile Gly
515 520 525
Ile Glu Lys Lys Glu Leu Glu Thr Phe Val Gln Asp Val Ser Asp Glu
530 535 540
Val Leu Gln Asp Glu Gln Leu Ile Glu Glu Glu Lys Leu Thr Glu Glu
545 550 555 560
Glu Lys Leu Thr Glu Glu Glu Lys Leu Thr Glu Glu Glu Lys Leu Thr
565 570 575
Glu Asp Glu Gln Leu Ile Glu Glu Glu Lys Leu Thr Glu Glu Glu Lys
580 585 590
Leu Thr Glu Glu Glu Lys Leu Thr Glu Glu Glu Lys Leu Thr Glu Glu
595 600 605
Glu Lys Leu Thr Glu Glu Glu Lys Leu Thr Glu Glu Glu Lys Leu Thr
610 615 620
Glu Glu Glu Lys Leu Thr Glu Glu Glu Lys Leu Thr Glu Glu Glu Ile
625 630 635 640
Phe Ile Glu Glu Asp Lys Ile Ser Pro Lys Glu Val Glu Glu Pro Leu
645 650 655
Glu Asp Val Leu Met Glu Lys Met Glu Lys Glu Tyr Lys Glu Ile Leu
660 665 670
His Glu Gly Lys Ser Val Val Thr Gln Asp Met Asp Glu Lys Leu Leu
675 680 685
Ser Glu Asn Leu Glu Asp Asp Leu Ile Pro Glu Glu Ile Ile Glu Glu
690 695 700
Leu Val Asp Glu Glu Leu Val Glu Glu Val Thr Ala Glu Glu Ile Val
705 710 715 720
Glu Glu Phe Val Ala Glu Val Glu Ile Glu Glu Lys Ile Pro Lys Glu
725 730 735
Leu Val Glu Glu Val Met Pro Glu Glu Asp Val Asp Glu Val Val Pro
740 745 750
Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Ile Glu Gly Val
755 760 765
Ile Pro Glu Glu Leu Val Glu Asp Val Ile Pro Glu Lys Val Leu Glu
770 775 780
Lys Val Ile Pro Glu Glu Ile Ile Glu Glu Leu Val Leu Glu Glu Val
785 790 795 800
Val Glu Glu Ile Lys His Glu Glu Leu Val Glu Glu Glu Ile Pro Glu
805 810 815
Glu Val Thr Glu Glu Val Ile Pro Asp Glu Val Val Glu Glu Val Ile
820 825 830
Pro Glu Glu Leu Ile Glu Lys Val Val Lys Glu Glu Leu Val Glu Lys
835 840 845
Val Val Ala Glu Glu Ile Val Glu Glu Val Val Pro Glu Glu Leu Val
850 855 860
Glu Lys Val Val Ala Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu
865 870 875 880
Leu Ile Glu Glu Val Ile Thr Glu Lys Pro Ala Glu Glu Val Ile Pro
885 890 895
Glu Glu Leu Val Glu Glu Val Ile Pro Lys Glu Ile Val Glu Glu Val
900 905 910
Leu Pro Glu Glu Val Val Lys Glu Val Ile Pro Glu Glu Val Val Glu
915 920 925
Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Ile
930 935 940
Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Met Lys Pro Glu
945 950 955 960
Glu Val Val Glu Glu Val Ile Ser Glu Glu Leu Val Glu Glu Met Lys
965 970 975
Pro Glu Glu Val Val Glu Glu Met Lys Pro Glu Glu Val Val Glu Glu
980 985 990
Val Thr Pro Glu Lys Val Val Glu Glu Val Val Pro Glu Glu Leu Val
995 1000 1005
Glu Glu Met Lys Pro Glu Glu Val Val Glu Glu Val Ile Ser Glu
1010 1015 1020
Glu Leu Val Glu Glu Met Lys Pro Glu Glu Val Val Glu Glu Val
1025 1030 1035
Thr Pro Glu Lys Val Val Glu Glu Val Val Pro Glu Glu Leu Val
1040 1045 1050
Glu Glu Met Lys Pro Glu Glu Val Val Glu Glu Val Ile Ser Glu
1055 1060 1065
Glu Leu Val Glu Glu Met Lys Pro Glu Glu Val Val Glu Glu Val
1070 1075 1080
Ile Ser Glu Glu Leu Val Glu Glu Met Lys Pro Glu Glu Val Val
1085 1090 1095
Glu Glu Val Thr Pro Glu Lys Val Val Glu Glu Val Val Pro Glu
1100 1105 1110
Glu Leu Val Glu Glu Met Lys Pro Glu Glu Val Val Glu Glu Val
1115 1120 1125
Ile Ser Glu Glu Leu Val Glu Glu Met Lys Pro Glu Glu Val Val
1130 1135 1140
Glu Glu Val Thr Pro Glu Lys Val Val Glu Glu Val Val Pro Glu
1145 1150 1155
Glu Leu Val Glu Glu Met Lys Pro Glu Glu Val Val Glu Glu Val
1160 1165 1170
Ile Ser Glu Glu Leu Val Glu Glu Met Lys Pro Glu Glu Val Val
1175 1180 1185
Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
1190 1195 1200
Glu Val Val Glu Glu Ile Ile Pro Glu Glu Val Val His Glu Ala
1205 1210 1215
Lys His Glu Glu Leu Phe Glu Lys Thr Val Pro Glu Val Glu Val
1220 1225 1230
Gln Glu Ile Ile Pro Lys Glu Leu Val Glu Val Ile Pro Glu Glu
1235 1240 1245
Val Leu Pro Glu Glu Leu Ile Glu Glu Val Ile Pro Glu Glu Ile
1250 1255 1260
Ile Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Ile Pro
1265 1270 1275
Glu Glu Ile Val Gln Glu Val Ile Pro Glu Asp Leu Met Glu Glu
1280 1285 1290
Val Val Pro Glu Glu Ile Ile Glu Glu Lys Ile Leu Glu Glu Ile
1295 1300 1305
Val Glu Glu Glu Ile His Glu Glu Ile Val Glu Glu Ile Ile Ser
1310 1315 1320
Glu Glu Val Val Glu Glu Val Val Pro Ala Glu Val Val Glu Glu
1325 1330 1335
Met Ile Pro Glu Lys Leu Val Glu Glu Val Ile Pro Glu Glu Leu
1340 1345 1350
Val Glu Glu Val Ile Ser Glu Glu Leu Val Glu Glu Val Val Pro
1355 1360 1365
Val Glu Val Leu Glu Glu Val Val Pro Val Glu Val Leu Glu Glu
1370 1375 1380
Val Ile Pro Glu Glu Val Val Glu Glu Val Ile Pro Glu Glu Phe
1385 1390 1395
Ile Glu Glu Met Ile Pro Glu Glu Ile Val Glu Glu Val Val Pro
1400 1405 1410
Glu Val Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val
1415 1420 1425
Val Pro Val Glu Leu Leu Glu Glu Val Ile Pro Glu Glu Leu Leu
1430 1435 1440
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu
1445 1450 1455
Glu Leu Val Glu Asp Val Ile Pro Glu Glu Leu Ile Ala Glu Val
1460 1465 1470
Val Ser Glu Glu Leu Val Glu Glu Glu Ile Pro Glu Glu Val Leu
1475 1480 1485
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
1490 1495 1500
Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Val
1505 1510 1515
Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu Val
1520 1525 1530
Glu Glu Glu Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
1535 1540 1545
Leu Leu Val Ala Glu Val Ile Pro Glu Glu Leu Val Ala Glu Val
1550 1555 1560
Ile Pro Glu Glu Phe Val Glu Glu Val Ile Pro Glu Glu Val Val
1565 1570 1575
Glu Glu Leu Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
1580 1585 1590
Glu Ile Val Glu Glu Val Val Glu Glu Val Val Glu Glu Ile Ile
1595 1600 1605
Pro Glu Glu Val Ile Glu Glu Val Ile Pro Glu Glu Ile Val Lys
1610 1615 1620
Glu Val Val Pro Glu Val Leu Val Glu Glu Val Val Pro Glu Glu
1625 1630 1635
Ile Val Glu Glu Val Val Pro Glu Glu Ile Val Glu Glu Val Val
1640 1645 1650
Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Ile Glu
1655 1660 1665
Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val
1670 1675 1680
Leu Val Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Met Val
1685 1690 1695
Leu Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu Val Glu
1700 1705 1710
Glu Met Val Pro Glu Glu Val Val Glu Lys Met Val Leu Glu Glu
1715 1720 1725
Val Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Ile
1730 1735 1740
Pro Glu Glu Asp Val Glu Gln Val Ile Pro Glu Glu Leu Ile Glu
1745 1750 1755
Glu Val Val Pro Glu Glu Val Ile Glu Glu Val Ile Thr Glu Glu
1760 1765 1770
Val Val Glu Glu Val Leu Pro Glu Glu Leu Val Glu Lys Val Val
1775 1780 1785
Glu Glu Glu Ile Leu Glu Glu Val Ile Pro Glu Glu Leu Val Glu
1790 1795 1800
Glu Val Val Arg Glu Glu Leu Ile Glu Glu Val Val Thr Glu Glu
1805 1810 1815
Leu Val Glu Lys Val Val Glu Glu Glu Ile Val Glu Glu Val Val
1820 1825 1830
Leu Ala Glu Val Val Glu Glu Val Ile Pro Gln Glu Ile Val Glu
1835 1840 1845
Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Ile Pro Lys Glu
1850 1855 1860
Ile Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Val
1865 1870 1875
Pro Glu Glu Leu Val Ala Glu Val Ile Pro Glu Glu Leu Val Ala
1880 1885 1890
Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val Val Thr Glu Glu
1895 1900 1905
Leu Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Ile
1910 1915 1920
Pro Glu Glu Val Val Glu Glu Val Val Pro Glu Glu Leu Val Glu
1925 1930 1935
Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu
1940 1945 1950
Ile Val Glu Glu Leu Leu Pro Lys Glu Val Val Glu Glu Val Ile
1955 1960 1965
Tyr Glu Glu Gln Val Glu Glu Val Ile Pro Glu Glu Leu Val Ala
1970 1975 1980
Glu Val Ile Pro Glu Lys Leu Val Glu Glu Val Ile Pro Glu Glu
1985 1990 1995
Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Val
2000 2005 2010
Pro Glu Val Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu
2015 2020 2025
Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu
2030 2035 2040
Val Glu Glu Glu Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro
2045 2050 2055
Glu Glu Leu Val Glu Glu Met Leu Pro Glu Glu Leu Ile Glu Val
2060 2065 2070
Val Val Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu
2075 2080 2085
Val Glu Glu Val Val Pro Glu Glu Val Val Glu Glu Val Ile Pro
2090 2095 2100
Glu Glu Leu Ile Glu Glu Leu Val Pro Glu Val Glu Ile Glu Glu
2105 2110 2115
Ile Leu Pro Glu Glu Leu Ile Glu Glu Leu Val Pro Glu Glu Ile
2120 2125 2130
Ile Glu Glu Val Ile Pro Lys Glu Leu Ile Glu Glu Val Ile Pro
2135 2140 2145
Glu Val Val Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val
2150 2155 2160
Val Pro Glu Ile Val Glu Glu Val Val Pro Glu Val Val Glu Glu
2165 2170 2175
Val Val Pro Glu Glu Ile Ile Glu Glu Lys Ile Ser Glu Glu Val
2180 2185 2190
Val Glu Glu Val Leu Pro Lys Glu Ile Val Glu Glu Val Ile Pro
2195 2200 2205
Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Ala Glu
2210 2215 2220
Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu
2225 2230 2235
Phe Glu Glu Glu Ile Pro Glu Val Val Val Glu Glu Val Val Pro
2240 2245 2250
Glu Val Val Glu Glu Glu Ile Pro Glu Val Val Val Glu Glu Val
2255 2260 2265
Val Pro Glu Val Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu
2270 2275 2280
Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val Ile Pro Glu Glu
2285 2290 2295
Val Ala Glu Glu Val Leu Pro Glu Glu Leu Ile Glu Glu Val Ile
2300 2305 2310
Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Ala
2315 2320 2325
Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Val Arg Glu Glu
2330 2335 2340
Leu Val Glu Glu Val Val Pro Glu Glu Val Val Glu Glu Val Ile
2345 2350 2355
Pro Lys Glu Ile Val Glu Glu Val Val Ser Glu Glu Val Val Glu
2360 2365 2370
Glu Val Ile Pro Lys Glu Ile Val Glu Glu Glu Val Pro Glu Glu
2375 2380 2385
Leu Val Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Val Pro
2390 2395 2400
Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu
2405 2410 2415
Val Val Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu
2420 2425 2430
Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val Gln Glu Gln
2435 2440 2445
Leu Val Glu Glu Phe Ile Pro Glu Glu Val Val Glu Glu Leu Val
2450 2455 2460
Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu
2465 2470 2475
Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Leu Pro Glu Glu
2480 2485 2490
Val Val Lys Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Ile
2495 2500 2505
Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu
2510 2515 2520
Glu Val Leu Pro Glu Glu Val Val Lys Glu Val Ile Pro Glu Glu
2525 2530 2535
Val Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile
2540 2545 2550
Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu
2555 2560 2565
Glu Val Val Ser Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu
2570 2575 2580
Ile Val Glu Glu Val Ile Pro Glu Glu Leu Leu Glu Glu Val Val
2585 2590 2595
Glu Glu Val Val Pro Glu Ile Val Glu Glu Val Val Pro Glu Val
2600 2605 2610
Val Glu Glu Val Ile Thr Glu Glu Val Ile Pro Glu Glu Leu Ile
2615 2620 2625
Lys Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
2630 2635 2640
Glu Ile Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val
2645 2650 2655
Ile Ser Glu Glu Val Val Glu Glu Val Val Pro Glu Val Val Val
2660 2665 2670
Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Leu Pro Lys
2675 2680 2685
Glu Ile Val Glu Glu Val Ile Ser Glu Lys Val Val Glu Glu Met
2690 2695 2700
Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Val Val
2705 2710 2715
Glu Glu Val Ile Pro Glu Val Glu Ile Glu Glu Ile Leu Pro Glu
2720 2725 2730
Glu Leu Ile Glu Glu Leu Val Ala Glu Glu Val Ile Glu Glu Val
2735 2740 2745
Ile Pro Lys Glu Leu Ile Glu Glu Val Ile Pro Glu Lys Leu Ile
2750 2755 2760
Glu Asp Val Val Pro Glu Glu Ile Val Glu Glu Val Leu Pro Glu
2765 2770 2775
Glu Val Val Lys Glu Val Ile Pro Glu Glu Val Val Glu Glu Val
2780 2785 2790
Leu Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Val Glu
2795 2800 2805
Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Leu Pro Lys Glu
2810 2815 2820
Val Val Glu Glu Val Ile Pro Glu Val Glu Ile Glu Glu Ile Leu
2825 2830 2835
Pro Glu Glu Ile Ile Glu Glu Leu Val Ala Lys Glu Val Ile Glu
2840 2845 2850
Glu Val Ile Pro Lys Glu Leu Ile Glu Glu Ala Ile Thr Glu Glu
2855 2860 2865
Val Val Glu Glu Met Ile Pro Glu Glu Ile Ile Glu Glu Val Val
2870 2875 2880
Pro Glu Glu Val Ile Glu Glu Val Ile Thr Glu Glu Val Val Glu
2885 2890 2895
Glu Val Val Pro Glu Glu Val Ile Glu Glu Val Ile Thr Glu Glu
2900 2905 2910
Val Val Glu Glu Ala Ile Pro Glu Glu Val Val Glu Glu Val Ile
2915 2920 2925
Pro Glu Val Glu Ile Glu Glu Val Leu Pro Glu Glu Leu Ile Glu
2930 2935 2940
Glu Leu Val Pro Glu Glu Val Thr Glu Glu Val Ile Thr Glu Glu
2945 2950 2955
Val Val Glu Glu Ala Ile Ser Glu Val Val Glu Glu Val Ile Pro
2960 2965 2970
Glu Glu Ile Val Lys Glu Val Ile Pro Glu Glu Val Val Glu Glu
2975 2980 2985
Ile Ile Thr Glu Glu Ile Ala Glu Glu Ile Ile Pro Lys Glu Leu
2990 2995 3000
Val Glu Glu Val Ile Pro Glu Glu Val Val Val Glu Ile Ile Pro
3005 3010 3015
Glu Lys Leu Val Glu Glu Phe Val Ser Glu Glu Leu Val Glu Glu
3020 3025 3030
Leu Val Pro Glu Glu Ile Val Glu Lys Val Val Pro Glu Glu Leu
3035 3040 3045
Val Glu Glu Ile Val Pro Glu Glu Leu Val Glu Glu Val Val Pro
3050 3055 3060
Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu
3065 3070 3075
Phe Ile Pro Glu Glu Val Val Glu Glu Val Leu Pro Glu Gln Leu
3080 3085 3090
Val Glu Glu Val Ile Ser Glu Val Val Glu Glu Val Val Pro Glu
3095 3100 3105
Glu Leu Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Leu
3110 3115 3120
Val Ala Glu Glu Val Ile Glu Glu Val Ile Pro Lys Glu Leu Ile
3125 3130 3135
Glu Glu Ala Ile Thr Glu Glu Val Glu Glu Val Ile Pro Glu Glu
3140 3145 3150
Ile Val Glu Glu Val Ile Pro Glu Glu Val Val Lys Glu Val Ile
3155 3160 3165
Pro Glu Val Glu Ile Glu Glu Ile Leu Pro Glu Glu Leu Ile Glu
3170 3175 3180
Glu Leu Val Ala Lys Glu Val Ile Glu Glu Val Ile Thr Glu Glu
3185 3190 3195
Val Ala Glu Glu Val Ile Pro Glu Glu Ile Val Gln Glu Val Ile
3200 3205 3210
Pro Glu Glu Val Val Glu Glu Ile Ile Thr Glu Val Glu Ile Glu
3215 3220 3225
Glu Val Leu Pro Glu Glu Leu Ile Asp Glu Val Val Pro Glu Glu
3230 3235 3240
Val Thr Glu Glu Val Ile Thr Glu Glu Val Met Pro Glu Glu Val
3245 3250 3255
Val Lys Glu Val Ile Pro Glu Glu Ile Ala Glu Glu Val Ile Pro
3260 3265 3270
Lys Glu Leu Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu
3275 3280 3285
Ile Ile Pro Glu Val Glu Ile Glu Glu Val Leu Pro Glu Glu Val
3290 3295 3300
Ile Glu Glu Val Val Pro Glu Val Glu Ile Glu Glu Leu Ile Pro
3305 3310 3315
Asp Glu Val Val Glu Glu Val Leu Pro Glu Glu Leu Val Glu Glu
3320 3325 3330
Val Ile Pro Glu Glu Val Ala Val Glu Val Val Pro Glu Glu Val
3335 3340 3345
Ile Glu Glu Ala Val Pro Glu Glu Ile Val Glu Glu Phe Ile Pro
3350 3355 3360
Glu Glu Gln Ile Glu Glu Val Ile Gln Glu Glu Ile Ile Glu Gln
3365 3370 3375
Val Val Pro Glu Glu Leu Ile Glu Glu Val Val Pro Glu Glu Ile
3380 3385 3390
Ile Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Ile Tyr
3395 3400 3405
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Ala Glu
3410 3415 3420
Lys Leu Val Lys Glu Ile Val Pro Glu Gln Val Arg Glu Glu Val
3425 3430 3435
Thr Leu Glu Glu Ile Val Glu Glu Met Ile Pro Glu Glu Phe Val
3440 3445 3450
Glu Glu Val Ala Pro Glu Val Glu Ile Glu Glu Ile Ile Pro Glu
3455 3460 3465
Glu Leu Ile Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Ala
3470 3475 3480
Val Pro Glu Glu Leu Ile Glu Lys Val Ile Pro Glu Val Leu Val
3485 3490 3495
Glu Glu Ile Ile Tyr Lys Glu Gly Ile Pro Glu Val Leu Ile Glu
3500 3505 3510
Glu Val Ile Pro Glu Glu Leu Val Gln Glu Val Ile Pro Glu Glu
3515 3520 3525
Ile Val Glu Glu Val Val Pro Glu Glu Phe Ile Glu Glu Met Ile
3530 3535 3540
Pro Gln Glu Val Val Lys Glu Val Ile Thr Glu Lys Phe Ile Glu
3545 3550 3555
Glu Met Ile Pro Glu Glu Val Val Glu Glu Val Ile Pro Glu Glu
3560 3565 3570
Phe Ile Glu Glu Met Ile Pro Glu Val Val Val Glu Glu Val Val
3575 3580 3585
Pro Glu Glu Leu Val Glu Glu Met Leu Pro Glu Glu Leu Ile Glu
3590 3595 3600
Val Val Val Pro Glu Glu Leu Ile Glu Glu Val Ile Pro Glu Glu
3605 3610 3615
Leu Val Glu Glu Val Val Ala Glu Glu Leu Val Glu Glu Val Ile
3620 3625 3630
Pro Glu Glu Leu Val Glu Lys Val Val Pro Glu Val Val Glu Glu
3635 3640 3645
Phe Ile His Glu Val Val Glu Glu Val Val Pro Glu Val Val Glu
3650 3655 3660
Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val
3665 3670 3675
Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val
3680 3685 3690
Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu
3695 3700 3705
Val Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro
3710 3715 3720
Glu Val Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val
3725 3730 3735
Ile Pro Glu Val Leu Phe Glu Glu Glu Ile Pro Glu Glu Leu Val
3740 3745 3750
Glu Val Val Pro Val Glu Leu Leu Glu Glu Ala Ile Pro Glu Glu
3755 3760 3765
Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile
3770 3775 3780
Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu
3785 3790 3795
Glu Val Ile Leu Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu
3800 3805 3810
Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile
3815 3820 3825
Pro Glu Val Leu Val Glu Glu Glu Ile Pro Glu Lys Leu Val Glu
3830 3835 3840
Glu Asp Ile Pro Glu Lys Leu Val Glu Glu Val Val Pro Glu Glu
3845 3850 3855
Leu Val Glu Val Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile
3860 3865 3870
Pro Glu Glu Leu Val Lys Glu Val Ile Pro Glu Glu Leu Val Lys
3875 3880 3885
Glu Val Val Pro Glu Glu Leu Val Glu Glu Glu Ile Pro Lys Val
3890 3895 3900
Val Glu Glu Val Leu Pro Glu Glu Leu Val Glu Glu Val Met Leu
3905 3910 3915
Glu Glu Val Val Glu Glu Val Val Pro Glu Ile Val Glu Glu Val
3920 3925 3930
Val Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Val Val Glu
3935 3940 3945
Glu Val Val Pro Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu
3950 3955 3960
Leu Val Glu Glu Val Val Lys Glu Glu Leu Val Glu Glu Val Val
3965 3970 3975
Lys Glu Glu Leu Val Glu Glu Val Val Lys Glu Glu Leu Val Glu
3980 3985 3990
Glu Val Ile Pro Glu Val Leu Val Glu Glu Val Val Pro Glu Glu
3995 4000 4005
Leu Leu Glu Glu Val Ile Pro Lys Val Leu Val Glu Glu Val Ile
4010 4015 4020
Pro Glu Leu Leu Val Glu Glu Val Val Pro Glu Val Ile Glu Glu
4025 4030 4035
Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Glu Leu Leu
4040 4045 4050
Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Glu Ile Pro Glu
4055 4060 4065
Lys Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val
4070 4075 4080
Ile Pro Glu Val Leu Val Glu Glu Val Val Pro Glu Glu Leu Val
4085 4090 4095
Glu Glu Val Ile Ser Glu Glu Leu Val Glu Glu Val Ile Pro Glu
4100 4105 4110
Glu Leu Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val
4115 4120 4125
Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val Glu Glu
4130 4135 4140
Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val Glu
4145 4150 4155
Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val
4160 4165 4170
Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val
4175 4180 4185
Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu
4190 4195 4200
Glu Leu Ile Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val
4205 4210 4215
Ile Pro Glu Glu Leu Val Ala Glu Val Ile Pro Glu Lys Leu Val
4220 4225 4230
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
4235 4240 4245
Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val
4250 4255 4260
Leu Pro Glu Glu Val Val Glu Glu Ala Val Pro Glu Val Val Glu
4265 4270 4275
Glu Ile Val Pro Glu Glu Leu Ile Glu Glu Val Ile Pro Glu Glu
4280 4285 4290
Leu Ile Lys Glu Val Val Pro Glu Glu Val Ile Glu Glu Val Ile
4295 4300 4305
Thr Glu Glu Val Val Glu Glu Val Leu Pro Glu Glu Ile Val Glu
4310 4315 4320
Glu Val Leu Pro Glu Glu Val Ile Glu Glu Val Val Pro Glu Glu
4325 4330 4335
Leu Val Glu Glu Val Leu Pro Glu Glu Val Val Glu Glu Val Val
4340 4345 4350
Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Glu
4355 4360 4365
Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Leu Pro Glu Glu
4370 4375 4380
Val Val Glu Glu Val Val Pro Lys Glu Leu Val Glu Glu Leu Ile
4385 4390 4395
Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu
4400 4405 4410
Glu Val Val Pro Glu Glu Leu Val Ala Glu Val Ile Pro Glu Glu
4415 4420 4425
Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile
4430 4435 4440
Pro Glu Glu Leu Val Glu Glu Glu Ile Pro Glu Glu Leu Val Glu
4445 4450 4455
Glu Val Ile Leu Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu
4460 4465 4470
Leu Ile Glu Glu Val Val Pro Glu Glu Leu Ile Glu Glu Val Val
4475 4480 4485
Pro Glu Glu Leu Ile Glu Glu Val Val Glu Lys Val Ile Pro Glu
4490 4495 4500
Glu Ile Ile Glu Glu Val Val Pro Glu Glu Val Ile Glu Glu Val
4505 4510 4515
Ile Thr Glu Glu Val Val Glu Glu Val Val Pro Glu Lys Val Ile
4520 4525 4530
Glu Glu Val Ile Thr Glu Glu Val Val Glu Glu Val Val Pro Glu
4535 4540 4545
Glu Val Ile Asp Glu Val Ile Thr Glu Glu Val Val Glu Glu Val
4550 4555 4560
Val Pro Glu Glu Val Ile Glu Glu Val Ile Ile Glu Glu Val Val
4565 4570 4575
Glu Glu Val Val Pro Glu Glu Val Ile Glu Glu Val Ile Thr Glu
4580 4585 4590
Glu Val Val Glu Glu Ala Ile Pro Glu Glu Leu Val Glu Glu Val
4595 4600 4605
Ile Pro Glu Val Leu Val Glu Glu Glu Ile Pro Glu Glu Leu Val
4610 4615 4620
Glu Glu Val Ile Leu Glu Glu Leu Val Glu Glu Val Val Ala Glu
4625 4630 4635
Glu Leu Ile Glu Glu Val Val Glu Glu Val Ile Pro Glu Lys Leu
4640 4645 4650
Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Ile Pro
4655 4660 4665
Glu Glu Leu Val Glu Val Val Val Pro Glu Glu Leu Val Glu Glu
4670 4675 4680
Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile His Glu Glu Leu
4685 4690 4695
Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile His
4700 4705 4710
Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu
4715 4720 4725
Val Ile Pro Glu Glu Ile Val Glu Glu Val Val Pro Glu Glu Leu
4730 4735 4740
Leu Glu Glu Val Ile Pro Glu Leu Leu Val Glu Glu Val Val Pro
4745 4750 4755
Glu Val Val Glu Glu Val Val Pro Val Glu Leu Leu Glu Glu Val
4760 4765 4770
Val Glu Glu Val Ile Thr Glu Glu Val Ile Pro Glu Glu Leu Ile
4775 4780 4785
Lys Glu Val Ile Ser Glu Glu Leu Val Glu Glu Leu Ile Pro Glu
4790 4795 4800
Glu Val Val Gln Glu Val Ile Thr Glu Glu Val Leu Glu Glu Val
4805 4810 4815
Ile Pro Glu Glu Ile Val Glu Glu Leu Ile Pro Glu Lys Leu Ile
4820 4825 4830
Gly Glu Val Val Pro Glu Lys Val Val Glu Glu Val Val Leu Glu
4835 4840 4845
Glu Val Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val
4850 4855 4860
Ile Thr Glu Glu Val Leu Ala Glu Glu Ile Val Glu Glu Phe Val
4865 4870 4875
Pro Glu Glu Leu Val Glu Glu Met Leu Pro Glu Glu Val Val Glu
4880 4885 4890
Glu Arg Val Arg Glu Val Glu Ile Glu Glu Met Val Pro Glu Val
4895 4900 4905
Leu Val Glu Glu Val Leu Pro Glu Val Val Glu Glu Val Ile Thr
4910 4915 4920
Glu Glu Val Val Glu Glu Met Val Pro Glu Glu Val Val Glu Glu
4925 4930 4935
Met Val Pro Lys Glu Ile Val Glu Glu Val Leu Pro Glu Glu Val
4940 4945 4950
Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Met Val Pro
4955 4960 4965
Glu Val Leu Val Glu Glu Val Val Pro Glu Glu Ile Val Glu Lys
4970 4975 4980
Val Val Pro Glu Glu Val Val Glu Glu Val Val Ala Glu Glu Ile
4985 4990 4995
Ile Glu Glu Val Ile Thr Glu Glu Val Val Glu Glu Ile Val Pro
5000 5005 5010
Gly Glu Val Val Glu Glu Met Val Pro Glu Glu Ile Ile Glu Glu
5015 5020 5025
Val Val Pro Glu Glu Val Ile Glu Glu Val Ile Thr Glu Glu Val
5030 5035 5040
Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro
5045 5050 5055
Glu Ile Ser Val Glu Val Glu Ile Pro Glu Val Leu Val Glu Glu
5060 5065 5070
Val Ile Pro Glu Lys Leu Val Lys Val Val Pro Glu Glu Leu Val
5075 5080 5085
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Thr Glu
5090 5095 5100
Ala Leu Val Glu Glu Val Val Asp Val Val Val Pro Glu Glu Ile
5105 5110 5115
Phe Glu Glu Val Leu Pro Glu Glu Val Val Glu Glu Val Ile Pro
5120 5125 5130
Glu Glu Val Val Glu Glu Met Val Pro Glu Glu Val Val Glu Glu
5135 5140 5145
Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Val
5150 5155 5160
Val Glu Lys Val Val Pro Glu Gln Leu Val Glu Lys Val Val Pro
5165 5170 5175
Glu Glu Leu Val Glu Lys Val Leu Pro Glu Glu Leu Val Glu Glu
5180 5185 5190
Val Val Pro Glu Glu Leu Ile Glu Glu Val Val Thr Glu Glu Val
5195 5200 5205
Ile Glu Glu Ile Ile Pro Glu Glu Ile Ile Glu Glu Ile Ile Pro
5210 5215 5220
Glu Glu Val Val Glu Glu Arg Val Ser Ile Glu Val Val Glu Glu
5225 5230 5235
Leu Val Pro Glu Glu Leu Ile Glu Glu Val Val Ala Glu Glu Ile
5240 5245 5250
Phe Glu Glu Val Val Pro Glu Lys Leu Ile Glu Glu Val Val Ala
5255 5260 5265
Glu Glu Leu Ile Glu Glu Met Val Pro Glu Val Val Glu Glu Val
5270 5275 5280
Val Glu Glu Ile Ile Pro Glu Glu Val Ile Glu Glu Val Ile Pro
5285 5290 5295
Glu Glu Ile Arg Glu Glu Ile Ile Pro Glu Glu Val Val Glu Glu
5300 5305 5310
Val Ile Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Glu Ile
5315 5320 5325
Ser Arg Glu Ile Val Glu Glu Val Ile Pro Glu Glu Val Val Glu
5330 5335 5340
Glu Met Met Pro Glu Glu Val Ile Glu Glu Val Ile Pro Glu Glu
5345 5350 5355
Ile Arg Glu Glu Met Ile Pro Glu Glu Val Val Glu Glu Met Ile
5360 5365 5370
Pro Glu Ile Glu Ile Glu Gln Val Leu Pro Glu Glu Leu Ile Glu
5375 5380 5385
Glu Leu Val Pro Glu Val Glu Ile Glu Glu Ile Leu Pro Glu Glu
5390 5395 5400
Leu Ile Glu Glu Leu Val Pro Glu Gly Val Ile Glu Glu Val Ile
5405 5410 5415
Pro Lys Glu Leu Ile Glu Glu Val Ile Pro Glu Glu Leu Ile Lys
5420 5425 5430
Glu Val Val Pro Glu Glu Val Val Glu Glu Val Ile Pro Lys Glu
5435 5440 5445
Ile Val Glu Glu Val Val Pro Glu Glu Leu Ile Glu Glu Val Ile
5450 5455 5460
Pro Glu Glu Leu Ile Glu Glu Val Val Pro Glu Glu Met Ile Glu
5465 5470 5475
Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val Val Pro Glu Glu
5480 5485 5490
Met Ile Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val Val
5495 5500 5505
Pro Glu Glu Val Lys Glu Glu Val Ile Pro Val Glu Leu Ile Glu
5510 5515 5520
Glu Val Val Pro Glu Glu Met Ile Glu Glu Val Ile Ser Glu Glu
5525 5530 5535
Val Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Leu
5540 5545 5550
Pro Glu Val Phe Val Glu Glu Ile Val Pro Lys Glu Leu Val Glu
5555 5560 5565
Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu
5570 5575 5580
Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile
5585 5590 5595
Ser Glu Glu Leu Leu Glu Glu Val Ile Pro Glu Leu Leu Val Glu
5600 5605 5610
Glu Val Val Pro Glu Val Ile Glu Glu Val Val Pro Glu Val Val
5615 5620 5625
Glu Glu Val Ile Pro Glu Val Val Glu Glu Val Val Thr Glu Glu
5630 5635 5640
Leu Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Met Ile
5645 5650 5655
Pro Gly Val Glu Ile Glu Glu Val Leu Pro Glu Glu Leu Val Glu
5660 5665 5670
Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Ile Ser Glu Glu
5675 5680 5685
Asp Phe Glu Glu Val Ile Pro Glu Ala Leu Val Glu Glu Val Ile
5690 5695 5700
Pro Glu Leu Leu Val Glu Glu Val Val Leu Glu Glu Leu Ile Glu
5705 5710 5715
Glu Val Ile Pro Glu Val Val Glu Glu Val Ile Pro Glu Glu Val
5720 5725 5730
Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Lys Val Val Pro
5735 5740 5745
Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu
5750 5755 5760
Val Ile Pro Glu Glu Val Pro Glu Glu Val Val Pro Glu Glu Leu
5765 5770 5775
Val Glu Glu Val Ile Ser Glu Glu Leu Val Glu Glu Val Ile Pro
5780 5785 5790
Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu
5795 5800 5805
Val Met Pro Glu Glu Val Ala Glu Glu Val Val Pro Glu Glu Leu
5810 5815 5820
Val Glu Glu Glu Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro
5825 5830 5835
Glu Val Leu Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu
5840 5845 5850
Val Val Pro Glu Glu Val Val Glu Val Val Ile Pro Glu Glu Phe
5855 5860 5865
Ile Glu Glu Ile Ile Pro Glu Glu Val Val Val Glu Val Thr Pro
5870 5875 5880
Glu Glu Leu Ile Glu Glu Met Lys Pro Glu Glu Leu Phe Glu Glu
5885 5890 5895
Val Ile Pro Lys Glu Leu Ile Glu Glu Ile Ile Pro Glu Glu Leu
5900 5905 5910
Ile Lys Glu Val Ile Pro Glu Glu Ile Ile Glu Glu Val Ile Ser
5915 5920 5925
Lys Glu Ile Val Glu Glu Val Val Glu Glu Glu Ile Ile Glu Glu
5930 5935 5940
Val Ile Pro Glu Glu Ile Val Glu Glu Val Val Pro Glu Glu Leu
5945 5950 5955
Val Glu Lys Lys Val Pro Glu Glu Ile Val Glu Glu Val Ile Tyr
5960 5965 5970
Glu Glu Phe Leu Glu Glu Ile Met Pro Glu Glu Leu Ile Glu Glu
5975 5980 5985
Met Lys Pro Glu Glu Leu Ile Glu Glu Ile Ile Pro Arg Glu Ile
5990 5995 6000
Val Glu Glu Ile Ile Thr Glu Glu Val Val Glu Glu Met Lys Pro
6005 6010 6015
Glu Glu Leu Val Glu Glu Met Val Pro Glu Glu Val Val Glu Glu
6020 6025 6030
Met Val Pro Glu Glu Val Val Glu Glu Met Val Pro Glu Glu Val
6035 6040 6045
Val Glu Glu Val Ile Thr Glu Lys Leu Ile Glu Glu Val Val Pro
6050 6055 6060
Glu Glu Ile Ile Glu Glu Leu Ile Pro Glu Glu Leu Val Glu Glu
6065 6070 6075
Val Ile Pro Glu Lys Leu Ile Glu Glu Met Ile Pro Glu Glu Val
6080 6085 6090
Val Glu Glu Met Leu Leu Glu Glu Val Val Glu Glu Val Val Pro
6095 6100 6105
Glu Val Glu Ile Glu Glu Met Ile Pro Glu Gln Leu Val Glu Glu
6110 6115 6120
Val Val Pro Glu Glu Leu Val Glu Lys Glu Ile Pro Glu Val Val
6125 6130 6135
Glu Glu Ile Ile Thr Glu Glu Val Val Glu Glu Met Val Pro Glu
6140 6145 6150
Glu Val Val Glu Glu Met Val Pro Glu Glu Val Val Glu Glu Val
6155 6160 6165
Ile Leu Glu Lys Leu Ile Glu Glu Val Val Pro Val Glu Val Ile
6170 6175 6180
Glu Glu Val Val Pro Glu Glu Val Ile Glu Glu Val Ile Pro Glu
6185 6190 6195
Lys Leu Ile Glu Glu Ile Ile Pro Glu Val Leu Val Glu Glu Val
6200 6205 6210
Val Pro Glu Glu Leu Ile Glu Glu Val Ile Pro Glu Val Leu Phe
6215 6220 6225
Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Glu
6230 6235 6240
Leu Val Glu Lys Val Val Pro Glu Glu Ile Val Glu Glu Val Ile
6245 6250 6255
Pro Glu Phe Val Glu Glu Val Ile Ser Glu Glu Ile Val Glu Glu
6260 6265 6270
Val Val Thr Glu Glu Leu Ile Glu Glu Met Ile Pro Glu Glu Val
6275 6280 6285
Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro
6290 6295 6300
Val Glu Leu Ile Glu Glu Val Val Pro Val Glu Leu Leu Glu Glu
6305 6310 6315
Val Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro Val Glu Leu
6320 6325 6330
Ile Glu Glu Val Val Pro Val Glu Leu Leu Glu Glu Val Ile Pro
6335 6340 6345
Glu Glu Val Val Glu Glu Val Ile Pro Glu Val Val Lys Glu Val
6350 6355 6360
Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val Glu Glu
6365 6370 6375
Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val Glu
6380 6385 6390
Glu Val Val Pro Glu Glu Leu Ile Glu Glu Val Ile Pro Glu Glu
6395 6400 6405
Leu Ile Lys Glu Val Leu Pro Glu Glu Val Ile Glu Glu Leu Lys
6410 6415 6420
Pro Glu Glu Leu Ile Glu Glu Ile Ile Pro Glu Glu Val Val Glu
6425 6430 6435
Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Met Ile Pro Glu Leu
6440 6445 6450
Leu Val Glu Glu Glu Val Pro Glu Glu Leu Val Glu Glu Val Ile
6455 6460 6465
Pro Glu Val Leu Val Glu Glu Met Val Pro Glu Glu Ile Val Glu
6470 6475 6480
Glu Val Ile Pro Glu Glu Leu Ile Ala Glu Phe Ala Pro Glu Glu
6485 6490 6495
Leu Phe Glu Lys Val Ile Pro Glu Glu Val Val Glu Glu Leu Val
6500 6505 6510
Ser Glu Glu Leu Val Glu Glu Val Leu Pro Glu Val Val Glu Glu
6515 6520 6525
Val Leu Pro Glu Val Phe Glu Glu Val Ile Pro Glu Glu Val Ile
6530 6535 6540
Glu Glu Ile Val Pro Glu Glu Val Met Glu Glu Val Val Pro Lys
6545 6550 6555
Glu Leu Ile Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val
6560 6565 6570
Ile Pro Glu Glu Val Ala Glu Glu Val Val Pro Glu Lys Leu Ile
6575 6580 6585
Glu Glu Val Ile Pro Glu Glu Leu Ile Lys Glu Val Val Pro Glu
6590 6595 6600
Glu Leu Ile Glu Glu Val Ile Thr Glu Glu Val Val Glu Glu Ala
6605 6610 6615
Ile Ser Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Val Val
6620 6625 6630
Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val Val Pro Glu
6635 6640 6645
Glu Leu Ile Glu Glu Ile Ile Pro Glu Glu Leu Val Glu Glu Val
6650 6655 6660
Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val
6665 6670 6675
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu
6680 6685 6690
Glu Leu Val Glu Lys Leu Ile Pro Glu Glu Leu Val Glu Glu Val
6695 6700 6705
Ile Pro Glu Leu Leu Val Glu Glu Val Val Pro Glu Glu Val Val
6710 6715 6720
Glu Glu Leu Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
6725 6730 6735
Glu Leu Val Glu Glu Val Ile Pro Glu Glu Val Pro Glu Glu Val
6740 6745 6750
Ile Arg Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val
6755 6760 6765
Glu Glu Val Ile Pro Glu Glu Val Pro Glu Glu Val Val Pro Glu
6770 6775 6780
Glu Leu Val Gln Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val
6785 6790 6795
Val His Glu Glu Val Pro Glu Glu Val Val Pro Glu Lys Leu Val
6800 6805 6810
Glu Glu Val Ile Pro Glu Glu Leu Phe Glu Glu Val Val Pro Glu
6815 6820 6825
Glu Val Pro Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val
6830 6835 6840
Ile Ser Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val
6845 6850 6855
Glu Glu Phe Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
6860 6865 6870
Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Phe
6875 6880 6885
Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val
6890 6895 6900
Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Glu Ile Pro Glu
6905 6910 6915
Lys Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val
6920 6925 6930
Ile Pro Glu Val Leu Val Glu Glu Val Val Thr Glu Glu Val Pro
6935 6940 6945
Glu Glu Val Val Pro Glu Glu Leu Val Ala Glu Val Val Pro Glu
6950 6955 6960
Glu Leu Val Lys Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val
6965 6970 6975
Ile Pro Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu Val Val
6980 6985 6990
Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
6995 7000 7005
Glu Val Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val
7010 7015 7020
Val Pro Val Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val
7025 7030 7035
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu
7040 7045 7050
Glu Ile Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val
7055 7060 7065
Ile Pro Glu Glu Ile Val Glu Glu Val Ile Ser Glu Glu Leu Ile
7070 7075 7080
Glu Glu Val Val Pro Val Glu Leu Leu Glu Glu Val Val Pro Val
7085 7090 7095
Glu Val Leu Glu Asp Val Ile Pro Glu Glu Val Val Glu Glu Val
7100 7105 7110
Ile Pro Glu Glu Phe Ile Glu Glu Met Ile Pro Glu Glu Ile Ile
7115 7120 7125
Glu Glu Ala Ile Pro Glu Glu Ile Val Glu Glu Val Ile Pro Glu
7130 7135 7140
Val Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile
7145 7150 7155
Pro Glu Glu Val Val Glu Lys Val Val Pro Glu Glu Leu Val Glu
7160 7165 7170
Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu
7175 7180 7185
Val Pro Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile
7190 7195 7200
Ser Glu Glu Leu Val Glu Glu Ile Ile Pro Glu Glu Leu Val Glu
7205 7210 7215
Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Val Pro Glu Glu
7220 7225 7230
Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile
7235 7240 7245
Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Val Glu Glu
7250 7255 7260
Val Ile Pro Glu Lys Leu Val Glu Glu Val Val Pro Glu Glu Leu
7265 7270 7275
Ile Glu Glu Met Ile Pro Glu Glu Ile Val Glu Glu Val Val Pro
7280 7285 7290
Glu Val Val Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val
7295 7300 7305
Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Lys Leu Ile
7310 7315 7320
Glu Glu Met Ile Pro Glu Glu Leu Val Glu Glu Val Ile Leu Glu
7325 7330 7335
Glu Val Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val
7340 7345 7350
Leu Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val
7355 7360 7365
Glu Glu Val Ala Pro Val Glu Leu Leu Glu Glu Val Ile Pro Glu
7370 7375 7380
Glu Leu Leu Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val
7385 7390 7395
Ile Pro Glu Glu Leu Val Glu Asp Val Ile Pro Glu Glu Leu Val
7400 7405 7410
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Ile Ile Pro Glu
7415 7420 7425
Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Glu
7430 7435 7440
Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val
7445 7450 7455
Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Leu Ile Pro Glu
7460 7465 7470
Val Leu Glu Glu Val Ile Pro Glu Lys Leu Val Glu Glu Val Val
7475 7480 7485
Pro Val Glu Leu Leu Glu Glu Val Ile Pro Glu Glu Leu Ile Glu
7490 7495 7500
Glu Val Val Pro Glu Val Leu Val Glu Val Ile Pro Glu Lys Val
7505 7510 7515
Val Glu Glu Val Ile His Glu Glu Ile Val Lys Glu Val Val Pro
7520 7525 7530
Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Ile Val Glu Glu
7535 7540 7545
Val Val Pro Glu Glu Val Leu Glu Glu Val Ile Pro Lys Val Leu
7550 7555 7560
Leu Glu Glu Glu Ile Pro Glu Lys Leu Val Glu Glu Val Ile Pro
7565 7570 7575
Glu Glu Leu Ile Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu
7580 7585 7590
Val Met Pro Glu Glu Val Val Glu Glu Val Val Pro Glu Glu Leu
7595 7600 7605
Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Ile Pro
7610 7615 7620
Glu Glu Leu Val Glu Glu Val Val Pro Val Glu Leu Leu Glu Glu
7625 7630 7635
Ile Val Pro Val Glu Leu Leu Glu Glu Val Ile Pro Glu Glu Leu
7640 7645 7650
Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro
7655 7660 7665
Glu Glu Leu Val Ala Glu Val Ile Pro Glu Lys Leu Val Glu Glu
7670 7675 7680
Val Ile Pro Glu Lys Leu Val Glu Glu Val Ile Pro Glu Glu Leu
7685 7690 7695
Val Glu Glu Val Val Pro Glu Glu Leu Val Ala Glu Val Ile Pro
7700 7705 7710
Glu Lys Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu
7715 7720 7725
Ile Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu
7730 7735 7740
Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro
7745 7750 7755
Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu
7760 7765 7770
Glu Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu
7775 7780 7785
Val Glu Glu Met Leu Pro Glu Glu Leu Ile Glu Val Val Val Pro
7790 7795 7800
Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu
7805 7810 7815
Val Val Pro Glu Glu Val Val Glu Glu Val Ile Pro Glu Glu Leu
7820 7825 7830
Ile Glu Glu Leu Val Pro Glu Val Glu Ile Glu Glu Ile Leu Pro
7835 7840 7845
Glu Glu Leu Ile Glu Glu Leu Val Pro Glu Glu Ile Ile Glu Glu
7850 7855 7860
Val Ile Pro Lys Glu Leu Ile Glu Glu Val Ile Pro Glu Val Val
7865 7870 7875
Val Glu Glu Val Val Pro Glu Val Leu Val Glu Glu Val Val Pro
7880 7885 7890
Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu
7895 7900 7905
Glu Val Pro Glu Glu Leu Val Glu Asp Val Ile Pro Glu Glu Leu
7910 7915 7920
Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro
7925 7930 7935
Glu Glu Val Val Glu Glu Val Leu Pro Glu Glu Leu Val Glu Glu
7940 7945 7950
Val Val Pro Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu Leu
7955 7960 7965
Val Glu Glu Glu Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro
7970 7975 7980
Glu Glu Val Val Glu Glu Val Ile Pro Glu Glu Val Pro Glu Lys
7985 7990 7995
Val Ile Pro Glu Lys Leu Val Glu Glu Leu Ile Pro Glu Glu Val
8000 8005 8010
Val Glu Glu Leu Ile Pro Glu Glu Val Val Glu Glu Met Val Pro
8015 8020 8025
Ile Glu Val Val Glu Glu Val Val Pro Thr Glu Val Leu Glu Glu
8030 8035 8040
Val Ile Pro Glu Ile Val Val Glu Glu Val Val Pro Glu Glu Leu
8045 8050 8055
Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro
8060 8065 8070
Glu Ile Val Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu
8075 8080 8085
Val Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu
8090 8095 8100
Val Glu Glu Val Val Pro Glu Glu Ile Val Glu Glu Leu Leu Pro
8105 8110 8115
Lys Glu Ile Val Glu Glu Val Ile Tyr Glu Glu Gln Val Glu Glu
8120 8125 8130
Val Ile His Glu Glu Leu Val Ala Glu Val Ile Pro Glu Glu Val
8135 8140 8145
Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu
8150 8155 8160
Ile Val Ala Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Val
8165 8170 8175
Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val
8180 8185 8190
Ile Pro Glu Glu Val Val Glu Glu Val Ile Pro Glu Glu Phe Ile
8195 8200 8205
Glu Glu Met Ile Pro Glu Glu Ile Val Glu Glu Val Val Pro Glu
8210 8215 8220
Val Val Glu Glu Val Ile Pro Glu Glu Leu Val Ala Glu Val Ile
8225 8230 8235
Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu Phe Glu
8240 8245 8250
Glu Glu Ile Pro Glu Val Val Val Glu Glu Val Val Pro Glu Val
8255 8260 8265
Val Glu Glu Glu Ile Pro Glu Val Val Val Glu Glu Val Val Pro
8270 8275 8280
Glu Val Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Leu
8285 8290 8295
Ile Pro Glu Glu Val Val Glu Glu Met Val Pro Ile Glu Ile Val
8300 8305 8310
Glu Glu Val Val Pro Thr Glu Val Leu Glu Glu Val Ile Pro Glu
8315 8320 8325
Ile Val Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val
8330 8335 8340
Ile Pro Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val
8345 8350 8355
Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val Pro Glu Val
8360 8365 8370
Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro
8375 8380 8385
Glu Val Val Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu
8390 8395 8400
Val Ile Pro Glu Glu Leu Val Glu Glu Ile Ile Pro Glu Glu Ile
8405 8410 8415
Val Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu Val Val Pro
8420 8425 8430
Glu Val Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu
8435 8440 8445
Val Ile Pro Glu Glu Leu Phe Glu Glu Val Val Pro Glu Glu Leu
8450 8455 8460
Val Ala Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Ile Pro
8465 8470 8475
Glu Glu Leu Ile Glu Glu Phe Val Pro Glu Glu Leu Val Glu Glu
8480 8485 8490
Glu Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Val Leu
8495 8500 8505
Val Glu Glu Val Ile Pro Glu Glu Phe Val Glu Glu Val Ile Pro
8510 8515 8520
Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu
8525 8530 8535
Val Ile Pro Glu Glu Val Val Glu Glu Val Val Pro Glu Ile Val
8540 8545 8550
Ala Glu Val Ile Pro Glu Glu Val Val Glu Glu Val Val Pro Glu
8555 8560 8565
Val Val Glu Glu Val Val Pro Glu Val Ile Glu Glu Val Val Pro
8570 8575 8580
Glu Val Ile Glu Glu Val Val Pro Glu Val Val Glu Glu Val Val
8585 8590 8595
Pro Glu Val Val Glu Glu Val Val Pro Glu Val Val Glu Glu Val
8600 8605 8610
Val Pro Val Glu Val Leu Glu Glu Val Ile Pro Glu Glu Val Val
8615 8620 8625
Glu Glu Val Ile Pro Glu Glu Phe Ile Glu Glu Met Ile Pro Glu
8630 8635 8640
Glu Ile Val Glu Glu Val Val Pro Glu Val Val Glu Asp Val Ile
8645 8650 8655
Pro Glu Glu Leu Ile Ala Glu Val Val Ser Glu Glu Leu Phe Glu
8660 8665 8670
Glu Glu Ile Pro Glu Glu Leu Val Glu Val Val Pro Val Glu Leu
8675 8680 8685
Leu Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro
8690 8695 8700
Glu Glu Leu Val Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu
8705 8710 8715
Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu
8720 8725 8730
Phe Glu Glu Val Val Pro Glu Glu Leu Val Glu Glu Val Ile Pro
8735 8740 8745
Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu
8750 8755 8760
Phe Val Pro Glu Glu Leu Val Glu Glu Glu Val Pro Glu Glu Leu
8765 8770 8775
Val Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Val Ile Pro
8780 8785 8790
Glu Glu Phe Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu
8795 8800 8805
Val Ile Pro Glu Glu Leu Phe Glu Glu Val Val Pro Glu Glu Leu
8810 8815 8820
Val Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Ile Pro
8825 8830 8835
Glu Glu Leu Ile Glu Glu Val Val Pro Glu Val Leu Val Glu Glu
8840 8845 8850
Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu
8855 8860 8865
Phe Glu Glu Val Val Pro Glu Glu Leu Val Ala Glu Val Ile Pro
8870 8875 8880
Glu Glu Ile Val Glu Glu Val Ile Pro Glu Glu Leu Ile Glu Glu
8885 8890 8895
Phe Val Pro Glu Glu Leu Val Glu Glu Glu Val Pro Glu Glu Leu
8900 8905 8910
Val Glu Glu Val Ile Pro Glu Val Leu Val Glu Glu Glu Val Pro
8915 8920 8925
Glu Glu Leu Val Glu Glu Val Ile Pro Glu Glu Leu Val Glu Glu
8930 8935 8940
Met Leu Pro Glu Glu Leu Ile Glu Val Val Val Pro Glu Glu Leu
8945 8950 8955
Val Glu Glu Val Val Pro Glu Ile Val Glu Glu Val Val Pro Glu
8960 8965 8970
Glu Leu Val Glu Glu Val Ile Pro Glu Glu Val Val Glu Glu Val
8975 8980 8985
Leu Pro Glu Lys Leu Val Glu Glu Val Val Pro Glu Ile Val Glu
8990 8995 9000
Glu Val Ala Pro Glu Val Val Glu Glu Val Ile Pro Glu Glu Leu
9005 9010 9015
Val Glu Glu Ile Ile Pro Glu Ile Leu Val Glu Glu Val Val Pro
9020 9025 9030
Ile Glu Val Val Glu Glu Ala Val Pro Glu Val Val Val Glu Glu
9035 9040 9045
Val Val Pro Glu Lys Ile Val Glu Glu Val Val Pro Glu Lys Val
9050 9055 9060
Leu Glu Glu Val Ile Pro Glu Leu Leu Val Glu Glu Ile Val Pro
9065 9070 9075
Ile Glu Val Val Gly Glu Ile Val Pro Glu Glu Val Val Glu Lys
9080 9085 9090
Ile Val Pro Met Glu Val Val Glu Glu Leu Leu Pro Glu Val Val
9095 9100 9105
Glu Glu Val Pro His Glu Ile Val Glu Glu Glu Val Val Lys Glu
9110 9115 9120
Val Ile Pro Glu Asp Glu Lys Lys Val Glu Ile Val Glu Ile Ile
9125 9130 9135
Ile Glu Glu Lys Val Glu Lys Ile Pro Lys Lys Lys Val Ile Glu
9140 9145 9150
Lys Lys Lys Glu Lys Glu Lys Ile Arg Lys Pro Lys Lys Lys Val
9155 9160 9165
Glu Lys Glu Ile Lys Pro Lys Glu Val Lys Gly Val Lys Gly Lys
9170 9175 9180
Leu Lys Lys Asp Val Lys Ala Lys His Leu Lys Gly Ser Lys Val
9185 9190 9195
Lys Ile Thr Glu Asp Ile Gln Lys Lys Met Glu Asp Asp Ile Lys
9200 9205 9210
Glu Lys Ile Met Glu Lys Glu Leu Lys Glu Glu Ile Lys Asp Lys
9215 9220 9225
Glu Tyr Leu Arg Lys Val Ile Pro Lys Glu Glu Lys Lys Glu Pro
9230 9235 9240
Ile Pro Lys Lys Gly Lys Ser Val Glu Pro Lys Lys Glu Lys Gln
9245 9250 9255
Ala Gly Val Lys Lys Glu Lys Val Pro Glu Thr Lys Lys Glu Lys
9260 9265 9270
Ala Pro Ala Pro Lys Lys Glu Lys Val Gln Ala Pro Lys Lys Glu
9275 9280 9285
Lys Val Pro Ala Pro Lys Lys Glu Lys Pro Ala Val Pro Lys Lys
9290 9295 9300
Glu Lys Val Pro Glu Pro Lys Lys Glu Lys Val Pro Glu Pro Lys
9305 9310 9315
Lys Glu Lys Ala Pro Ala Pro Lys Lys Glu Lys Val Gln Ala Pro
9320 9325 9330
Lys Lys Glu Lys Ala Pro Ala Pro Lys Lys Glu Lys Ala Pro Ala
9335 9340 9345
Pro Lys Lys Glu Lys Ala Pro Ala Pro Lys Lys Glu Lys Ala Pro
9350 9355 9360
Ala Pro Lys Lys Glu Lys Pro Ala Val Pro Lys Lys Glu Lys Pro
9365 9370 9375
Ala Val Pro Lys Lys Glu Lys Val Pro Glu Thr Lys Lys Glu Lys
9380 9385 9390
Val Pro Glu Thr Lys Lys Glu Lys Val Pro Glu Thr Lys Lys Glu
9395 9400 9405
Lys Val Pro Val Pro Lys Lys Glu Lys Val Pro Ala Pro Lys Lys
9410 9415 9420
Glu Lys Val Pro Ala Pro Lys Lys Glu Lys Val Pro Ala Pro Lys
9425 9430 9435
Lys Glu Lys Pro Ala Val Pro Lys Lys Glu Lys Val Pro Glu Thr
9440 9445 9450
Lys Lys Glu Lys Ala Pro Glu Pro Lys Lys Glu Lys Ala Pro Glu
9455 9460 9465
Pro Lys Lys Glu Lys Ala Pro Glu Pro Lys Lys Glu Lys Ala Pro
9470 9475 9480
Glu Pro Lys Lys Glu Lys Ala Pro Ala Pro Lys Lys Glu Lys Val
9485 9490 9495
Pro Val Pro Lys Lys Glu Lys Val Pro Ala Pro Lys Lys Glu Lys
9500 9505 9510
Val Pro Ala Pro Lys Lys Glu Lys Pro Ala Val Pro Lys Lys Glu
9515 9520 9525
Lys Val Pro Glu Thr Lys Lys Glu Lys Glu Lys Asp Ser Gln Pro
9530 9535 9540
Lys Lys Glu Lys Ala Lys Glu Thr Ser Arg Pro Pro Lys Lys Glu
9545 9550 9555
Lys Glu Lys Gly Lys
9560
<210> 57
<211> 133
<212> PRT
<213> 恶性疟原虫
<400> 57
Ile Pro Glu Glu Gln Ile Glu Glu Val Ile Gln Glu Glu Ile Ile Glu
1 5 10 15
Gln Val Val Pro Glu Glu Leu Ile Glu Glu Val Val Pro Glu Glu Ile
20 25 30
Ile Glu Glu Val Ile Pro Glu Glu Ile Val Glu Glu Val Ile Tyr Glu
35 40 45
Glu Val Ile Pro Glu Glu Leu Val Glu Glu Val Ile Ala Glu Lys Leu
50 55 60
Val Lys Glu Ile Val Pro Glu Gln Val Arg Glu Glu Val Thr Leu Glu
65 70 75 80
Glu Ile Val Glu Glu Met Ile Pro Glu Glu Phe Val Glu Glu Val Ala
85 90 95
Pro Glu Val Glu Ile Glu Glu Ile Ile Pro Glu Glu Leu Ile Glu Glu
100 105 110
Val Ile Pro Glu Val Leu Val Glu Glu Ala Val Pro Glu Glu Leu Ile
115 120 125
Glu Lys Val Ile Pro
130
<210> 58
<211> 6093
<212> PRT
<213> 恶性疟原虫
<400> 58
Met Ser Asn Ile Asn Asn Lys Asp Ser Ser Thr Glu Trp Asn Cys Lys
1 5 10 15
Glu Asp Val Gly Cys Val Pro Pro Arg Arg Gln Asn Leu Asn Met Glu
20 25 30
Arg Leu Asp Asn Glu Asn Glu Asp Ser Val Pro Asp Phe Met Lys Lys
35 40 45
Thr Phe Tyr Leu Ala Ala Ala Gly Glu Gly Lys Lys Leu Arg Glu Lys
50 55 60
His Asp Glu Ser Cys Asp Glu Phe Cys Asp Ala Trp Asn Arg Ser Leu
65 70 75 80
Ala Asp Tyr Lys Asp Ile Phe Gln Gly Lys Asp Met Trp Asn Asp Gly
85 90 95
Lys Tyr Gly Glu Ala Lys Asn His Ile Lys Asn Ala Phe Gly Asp Met
100 105 110
Asn Asn Arg Lys Thr Met Leu Asn Glu Ile Glu Lys Gly Ile Lys Asp
115 120 125
Glu Thr Phe Ser Arg Glu Asn Gly Leu Asp Val Cys Lys Ser Gln Cys
130 135 140
Glu Glu Arg Ser Arg Asp Asp Thr Glu Asp Gln Phe Leu Arg Phe Phe
145 150 155 160
Ala Glu Trp Glu Glu Glu Phe Cys Asp Gly Leu Asn Lys His Glu Glu
165 170 175
Gln Leu Lys Ser Cys Thr Lys Asp Ile Asn Cys Asp Ile Lys Cys Ser
180 185 190
Asn Phe Lys Asp Trp Leu Glu Thr Lys Lys Asp Glu Tyr Asp Ile Gln
195 200 205
Ser Arg Val Phe Glu Lys Lys Tyr Ala Asn Asp Asn Lys Ser Lys His
210 215 220
Leu Asn Tyr Leu Lys Glu Gly Met Asn Lys Cys Lys Val Lys Asn Pro
225 230 235 240
Glu Met Val Phe Lys Ser Gly Phe Ala Asn Val Ala Glu Cys Arg Asn
245 250 255
Leu Asn Val Glu Gly Ala Gly Asn Lys Asn Ser Asn Asn Leu Lys Asp
260 265 270
Leu Asp Ser Asn Ser Asp Lys Asp Gly Ile Val Ser Glu Ser Tyr Lys
275 280 285
Ala Thr Lys Lys Asn Gly Glu Ser Ile Met Asp Arg Ile Pro Lys Ser
290 295 300
Phe Asn Lys Leu Phe Gly Tyr Phe Ser Gly Ser Gln Glu Glu Glu Gln
305 310 315 320
Lys Glu Asn Asp Val Ser His Arg Asn Asn Tyr Asp Asn Ile Leu Val
325 330 335
Asp Lys Phe His Arg Ser Ser Leu Leu Asp Lys Leu Asp Asp Arg Met
340 345 350
Phe Phe Asp Glu Leu Asn Arg Asp Asn Ile Met Glu Glu Val Leu Ser
355 360 365
Lys Ile Pro Glu Pro Ile Ile Arg Glu Ala Pro Lys Tyr Val Pro Lys
370 375 380
Lys Pro Val Pro Pro Gln His Ile Pro Arg Gly Asp Asn Val Pro Arg
385 390 395 400
Asn Ile Asp Val Asn Gly Ser Lys Asp Glu Tyr Ser Pro Glu Thr Glu
405 410 415
Ser Ala Asn Ser Lys Ile Lys Pro Thr Tyr Glu Glu Asn Asp Glu Asp
420 425 430
Lys Ser Lys Ile Ser Ile Glu Thr Ser Glu Ile Asp Arg Asp Lys Glu
435 440 445
Pro Phe Arg Ile Ser Glu Glu Lys Lys Val Val Lys Glu Asp Val Gln
450 455 460
Glu Leu Glu Asn Ile Glu Tyr Glu Phe Asp Glu Thr Phe Asp Phe Phe
465 470 475 480
Asp Glu Asp Ala Lys Arg Asn Ile Asp Asp Ile Arg Lys Asp Ile Gln
485 490 495
Ser Gln Ile Met Lys Ser Val Glu Asn Tyr Asn Ser Glu Lys Glu Glu
500 505 510
Phe Lys Arg Asn Ile Glu Thr Gln Leu Ile Glu Ser Gly Asp Gly Met
515 520 525
Asn Ala Gly Asn Tyr Ser Ser Ala Leu Gln Asp Asn Ser Thr Glu Ile
530 535 540
Pro Thr Met Val Leu Val Pro Gly Val Leu Thr Val Phe Leu Leu Thr
545 550 555 560
Ile Ile Trp Val Leu Val Tyr Lys His Ser Leu Ile Asp Arg Val His
565 570 575
Gly Thr Gly Lys Thr Lys Lys Glu Glu Lys Met Lys Glu Leu Glu Ser
580 585 590
Glu Glu Phe Pro Lys Glu Lys Tyr Asn Ile Glu Asp Met Glu Glu Thr
595 600 605
Glu Lys Glu Asn Glu Ile Glu Lys Ile Met Asp Glu Asn Lys Glu Thr
610 615 620
Glu Gln Thr Glu Glu Gly Asn Thr Glu Glu Phe Val Gln Glu Lys Glu
625 630 635 640
Leu Asn Gln Glu Thr Leu Glu Asn Glu Ile Ile Val Asp His Ile Lys
645 650 655
Glu Glu Glu Asp Thr Arg Asn Val Lys Glu Gln Glu Ser Val Leu Glu
660 665 670
Glu Ser Pro Ile Glu Glu Leu Pro Val Glu Asn Asn Ile Gly Lys Ile
675 680 685
Asn Glu Glu Val Glu Glu Phe Ile Leu Asn Glu Ile Pro Leu Glu Glu
690 695 700
Gln Val Pro Lys Glu Leu Pro Gln Glu Glu Ile Glu Glu Ile Val Val
705 710 715 720
Glu Glu Leu Pro Ile Asp Glu His Leu Ser Ser Glu Glu Thr Thr Val
725 730 735
Thr Glu Glu Asp Thr Phe Lys Gly Gln Leu Ile Asn Glu Glu Lys Pro
740 745 750
Val Glu Glu Lys Ser Val Ser Glu Glu Ile Pro Val Glu Glu Lys Ser
755 760 765
Val Ser Glu Glu Ile Pro Val Glu Glu Lys Ser Val Ser Glu Glu Ile
770 775 780
Pro Val Glu Glu Lys Ser Val Ser Glu Glu Ile Pro Val Glu Glu Lys
785 790 795 800
Asn Val Ser Glu Glu Ile Pro Val Glu Glu Lys Asn Val Ser Glu Glu
805 810 815
Ile Pro Val Glu Glu Lys Asn Val Ser Glu Glu Ile Pro Val Glu Glu
820 825 830
Glu Asn Val Ser Glu Glu Ile Pro Glu Gly Gly Ile Ala Ile Glu Asp
835 840 845
Val Pro Val Asp Glu Glu Thr Val Thr Glu Glu Ile Thr Val Asp Glu
850 855 860
Lys Ile Tyr Asp Lys Leu Pro Asn Glu Ile Glu Thr Val Asn Glu Glu
865 870 875 880
Met Pro Val Glu Asp Glu Thr Leu Thr Glu Gln Ile Ser Ser Glu His
885 890 895
Glu Arg Val Pro Glu Glu Ile Ile Glu Glu Lys Pro Phe Thr Glu Gly
900 905 910
Glu Glu Thr Glu Ser Leu Thr Asp Glu Ile Val Glu Glu Gly Val Val
915 920 925
Thr Asp Asp Ile Pro Glu Glu Gln Ile Ile Thr Glu Lys Val Gln Glu
930 935 940
Glu Glu Glu Phe Val Thr Gly Glu Leu Ser Glu Glu Asp Ile Ile Asn
945 950 955 960
Glu Lys Val Gln Glu Glu Asp Glu Ser Val Thr Glu Glu Leu Pro Glu
965 970 975
Glu Asp Ile Ile Asn Glu Lys Val Gln Glu Glu Glu Glu Ser Ala Tyr
980 985 990
Gln Glu Ile Val Gln Asp Gly Ser Val Thr Lys Asp Val Glu Tyr Lys
995 1000 1005
Glu Leu Val Asn Asp Asp Val Arg Asp Lys Glu Asn Phe Val Ile
1010 1015 1020
Glu Glu Asp Pro Phe Lys Gly Gln Leu Ile Asn Glu Gly Leu Pro
1025 1030 1035
Val Glu Glu Glu Phe Val Thr Lys Glu Leu Pro Val Lys Glu Glu
1040 1045 1050
Ser Val Phe Glu Glu Leu Thr Glu Glu Asp Gln Ser Val Thr Lys
1055 1060 1065
Glu Ile Pro Val Glu Glu His Ser Val Phe Lys Glu Val Asp Glu
1070 1075 1080
Ile Glu Ser Val Thr Asp Glu Ile Val Glu Glu Glu Gly Ser Val
1085 1090 1095
Asn Glu Glu Val Glu Glu Glu Val Ser Val Ser Gly Glu Val Asp
1100 1105 1110
Glu Thr Glu Tyr Val Thr Glu Glu Val Glu Glu Thr Glu Leu Val
1115 1120 1125
Asn Glu Glu Val Leu Lys Glu Glu Gly Ser Ala Ser Glu Lys Val
1130 1135 1140
Val Lys Glu Glu Gly Ser Ala Ser Glu Lys Ile Val Glu Glu Glu
1145 1150 1155
Gly Ser Val Thr Glu Glu Thr Ala Ser Glu Glu Ile Val Glu Glu
1160 1165 1170
Glu Gly Ser Val Thr Glu Glu Ser Ser Ser Glu Glu Ile Val Glu
1175 1180 1185
Asp Glu Gly Ser Val Thr Glu Glu Ser Ser Ser Glu Glu Ile Val
1190 1195 1200
Glu Glu Glu Gly Ser Val Ile Glu Glu Ser Ala Ser Glu Val Ile
1205 1210 1215
Val Glu Asp Glu Val Ser Ala Ser Lys Glu Ile Val Glu Asp Glu
1220 1225 1230
Ala Ser Val Thr Glu Glu Val Val Glu Glu Glu Gly Ala Val Ser
1235 1240 1245
Asp Glu Val Gln Val Thr Glu Ser Val Glu Asp Glu Ile Ile Asn
1250 1255 1260
Gln Gly Ile Val Asp Glu Val Ile Val Glu Gln Glu Ala Ser Val
1265 1270 1275
Thr Asp Glu Ile Val Lys Glu Asp Glu Ser Val Ile Glu Glu Ile
1280 1285 1290
Ala Val Glu Glu Thr Val Thr Glu Val Val Glu Glu Thr Lys Pro
1295 1300 1305
Met Asp Glu Glu Ile Val Asp Gln Gly Ser Val Val Glu Asn Val
1310 1315 1320
Glu Glu Lys Lys Thr Met Asp Glu Glu Ile Val Asp Gln Gly Ser
1325 1330 1335
Val Val Glu Asn Val Glu Glu Lys Lys Thr Met Asp Glu Glu Ile
1340 1345 1350
Gly Asp Gln Gly Ser Val Ala Glu Lys Val Glu Glu Glu Glu Leu
1355 1360 1365
Val Thr Glu Glu Val Ile Glu Arg Glu Gly Ser Ile Asn Glu Asp
1370 1375 1380
Ile Val Lys Glu Ala Ser Ile Thr Glu Glu Val Glu Gln Ile Glu
1385 1390 1395
Pro Val Thr Gly Lys Val Glu Lys Ile Glu Ser Ile Thr Asp Glu
1400 1405 1410
Ile Lys Glu Gln Leu Val Pro Glu Asp Ile Lys Glu Glu Gln Leu
1415 1420 1425
Asp Phe Glu Glu Ile Val Ala Gln Arg Ala Ser Val Asn Asp Glu
1430 1435 1440
Lys Val Glu Val Ala Ser Ile Thr Glu Glu Val Glu Glu Glu Glu
1445 1450 1455
Lys Ser Val Ser Glu Glu Val Leu Glu Glu Glu Gly Ser Thr Thr
1460 1465 1470
Glu Lys Val Val Lys Gly Ser Ser Thr Glu Val Val Val Glu Glu
1475 1480 1485
Gln Gly Ser Val Thr Glu Asn Leu Leu Glu Glu Glu Ser Ala Ser
1490 1495 1500
Gln Gly Ile Val Glu Lys Glu Glu Phe Val Asp Glu Glu Asp Ser
1505 1510 1515
Val Lys Asp Gln Asn Val Phe Glu Lys Glu Gly Ser Val Thr Glu
1520 1525 1530
Gln Leu Val Glu Glu Glu Lys Gly Leu Ile Asn Glu Asp Asn Glu
1535 1540 1545
Lys Glu Glu Leu Ile Thr Glu Met Ser Glu Glu Ile Lys Ser Val
1550 1555 1560
Asn Glu Glu Ile Glu Glu Thr Asp Leu Ser Thr Glu Glu Ile Ile
1565 1570 1575
Lys Gln Gln Gly Leu Ala Thr Tyr Glu Phe Val Glu Glu Glu Lys
1580 1585 1590
Ser Leu Thr Asp Lys Leu Leu Glu Glu Glu Ser Val Thr Lys Glu
1595 1600 1605
Val Gly Glu Thr Glu Leu Ser Thr Gln Glu Val Val Asp Glu Lys
1610 1615 1620
Val Ser Val Thr Glu Glu Val Ile Glu Glu Glu Lys Ser Val Ser
1625 1630 1635
Glu Glu Val Leu Glu Glu Gly Ser Ala Thr Glu Glu Val Val Glu
1640 1645 1650
Glu Gly Ser Cys Thr Glu Val Val Val Glu Glu Gly Ser Cys Thr
1655 1660 1665
Glu Val Val Val Glu Glu Gly Ser Cys Thr Glu Ile Val Val Glu
1670 1675 1680
Lys Gly Ser Asp Thr Glu Ile Val Val Glu Glu Gly Ser Ala Thr
1685 1690 1695
Glu Ile Val Val Glu Glu Gly Ser Ala Thr Glu Val Val Val Glu
1700 1705 1710
Glu Gly Ser Ala Thr Glu Glu Val Val Glu Glu Gly Ser Val Ser
1715 1720 1725
Glu Glu Met Leu Glu Glu Glu Gly Ser Ala Thr Glu Glu Val Val
1730 1735 1740
Glu Glu Gly Leu Ser Ser Asp Asn Val Gln Lys Ser Lys Gly Val
1745 1750 1755
Ile Glu Asn Val Gly Glu Ile Tyr Ser Val Lys Thr Ala Lys Asp
1760 1765 1770
Glu Ser Met Asn Glu Lys Ile Pro Leu Glu Lys Ser Ser Phe Val
1775 1780 1785
Asp Asp Glu Ser Phe Lys Gly Gln Gly Pro Thr Asp Asn Val Ser
1790 1795 1800
Val Glu Asp Val Asn Ser Glu Asp Ile Ile Asn Glu His Thr Pro
1805 1810 1815
Leu Glu Glu Thr Lys Ile Glu Glu Leu Pro Thr Glu Tyr Ile Thr
1820 1825 1830
Thr Ala Asp Ile His Thr Lys Gly Glu Thr Glu Thr Lys Tyr Asn
1835 1840 1845
Leu Ile Tyr Glu Lys Ile Asn Glu Glu Val Glu Lys Ala Lys Phe
1850 1855 1860
Gln Glu Glu Lys Ile Thr Glu Asn Ile Pro Val Glu Arg Glu Ser
1865 1870 1875
Val Thr Glu Asp Ile Val Gln Glu Pro Ser Leu Ala Gln Glu Val
1880 1885 1890
Glu Gln Lys Glu Ser Asp Thr Asn Glu Ile Glu Glu Thr Lys Leu
1895 1900 1905
Ala Asn Glu Lys Ile Ile Pro Glu Val Ser Val Thr Glu Asn Val
1910 1915 1920
Val Glu Lys Glu Gly Leu Asp Thr Glu Glu Val Leu Glu Glu Asp
1925 1930 1935
Glu Ser Ile Thr Glu Glu Ile Val Glu Glu Glu Val Ser Ser Ser
1940 1945 1950
Glu Glu Ile Val Glu Glu Glu Glu Ser Ser Ser Glu Glu Ile Val
1955 1960 1965
Glu Glu Glu Glu Ser Ser Ser Glu Glu Ile Val Glu Glu Glu Glu
1970 1975 1980
Ser Ser Ser Glu Glu Ile Val Glu Glu Glu Glu Ser Ser Ser Glu
1985 1990 1995
Glu Ile Val Glu Glu Glu Glu Ser Ser Ser Glu Glu Ile Ile Glu
2000 2005 2010
Glu Val Ser Ser Thr Glu Glu Val Leu Glu Glu Glu Gly Ser Val
2015 2020 2025
Thr Glu Glu Ile Val Glu Glu Glu Val Ser Thr Thr Glu Glu Val
2030 2035 2040
Lys Asp Ile Gly Ser Val Ser Glu Glu Val Leu Glu Glu Glu Gly
2045 2050 2055
Phe Gly Thr Glu Glu Phe Val Gly Gln Gln Gly Ser Val Ile Glu
2060 2065 2070
Glu Ile Val Glu Thr Glu Ser Ser Thr Glu Lys Val Leu Glu Asp
2075 2080 2085
Val Gly Ser Asn Val Glu Glu Ile Val Gln Glu Glu Gly Pro Val
2090 2095 2100
Ala Gln Glu Ile Val His Glu Glu Val Ser Thr Thr Glu Lys His
2105 2110 2115
Asp Glu Val Asp Arg Ser Thr Thr Glu Glu Ile Val Glu Lys Val
2120 2125 2130
Gly Ser Val Ser Glu Glu Ile Ile Val Glu Glu Val Ser Ala Ser
2135 2140 2145
Glu Glu Ile Val Glu Glu Gly Ser Val Thr Glu Glu Val Val Glu
2150 2155 2160
Glu Glu Lys Leu Ile Asn Glu Val Gly Glu Thr Glu Ser Val Thr
2165 2170 2175
Glu Glu Ile Val Gln Lys Glu Val Ser Asp Ala Glu Glu Val Leu
2180 2185 2190
Gly Gln Glu Gly Ser Met Asn Glu Glu Ile Leu Glu Lys Glu Ser
2195 2200 2205
Ile Val Glu Glu Ile Val Gly Pro Glu Gly Ser Val Thr Glu Glu
2210 2215 2220
Ile Val Asp His Gly Ser Phe Ala Glu Glu Val Lys Glu Glu Glu
2225 2230 2235
Leu Val Thr Glu Glu Ala Val Gln Tyr Glu Gly Ser Val Thr Glu
2240 2245 2250
Glu Ile Lys Glu Glu Glu Ser Ile Thr Glu Asn Glu Ala Ile Glu
2255 2260 2265
Glu Ser Ala Phe Ala Glu Ile Ile Glu Glu Lys Gly Pro Asn Thr
2270 2275 2280
Asp Glu Ile Val Lys Glu Glu Gly Leu Asp Thr Glu Glu Ile Val
2285 2290 2295
Asn Glu Val Ser Val Thr Asp Glu Val Ile Glu Glu Glu Lys Leu
2300 2305 2310
Val Asn Glu Gln Ile Val Gly Glu Glu Arg Ser Val Thr Glu Lys
2315 2320 2325
Pro Val Glu Val Glu Arg Ser Ala Thr Glu Asp Leu Val Glu Glu
2330 2335 2340
Glu Ala Ser Val Thr Glu Lys Val Ser Val His Glu Gly Ser Thr
2345 2350 2355
Thr Glu Gln Ile Leu Asp Glu Ser Val Ala Glu Glu Ile Val Glu
2360 2365 2370
Glu Glu Val Ser Val Asp Asp Lys Ile Ile Glu Glu Glu Val Ser
2375 2380 2385
Val Asp Glu Val Val Glu Glu Glu Gly Ser Val Ile Glu Glu Ile
2390 2395 2400
Val Glu Glu Glu Glu Ser Val Pro Glu Glu Ile Leu Glu Glu Glu
2405 2410 2415
Leu Ser Gly Ser Glu Glu Val Leu Glu Asp Glu Trp Val Thr Asp
2420 2425 2430
Ala Phe Met Gly Gln Glu Gly Ser Val Ile Glu Glu Ile Glu Glu
2435 2440 2445
Ile Val Asp Gly Glu Gly Ser Ile Thr Glu Glu Ile Val Glu Asp
2450 2455 2460
Gly Ser Ala Asn Glu Lys Ile Val Glu Glu Glu Pro Ser Arg Val
2465 2470 2475
Glu Glu Val Leu Gly Lys Glu Gly Phe Val Ile Glu Glu Ile Ile
2480 2485 2490
Glu Glu Gly Ser Val Ile Glu Gln Val Glu Asp Thr Lys Thr Val
2495 2500 2505
Ser Glu Lys Ser Glu Glu Ser Ser Ala Ile Glu Glu Val Lys Glu
2510 2515 2520
Val Lys Glu Glu Glu Ser Ile Ser Glu Lys Ile Val Glu Lys Glu
2525 2530 2535
Glu Ser Val Thr Glu Glu Ile Val Arg Gln Glu Glu Ser Thr Thr
2540 2545 2550
Glu Lys Ile Val Lys Asp Val Ser Pro Thr Glu Asp Phe Val Glu
2555 2560 2565
Gln Thr Asp Ser Val Thr Glu Lys Val Ile Glu Gln Glu Gly Ser
2570 2575 2580
Asn Thr Glu Val Ala Glu Asp Val Glu Glu Lys Glu Ser Ala Ser
2585 2590 2595
Asp Glu His Glu Gln Glu Asp Val Ser Val Asn Ala Gln Val Thr
2600 2605 2610
Tyr Glu Lys Lys Ser Val Thr Lys Glu Ile Val Asp Glu Val Ser
2615 2620 2625
Arg Thr Glu Glu Ile Val Glu Glu Asn Gly Ser Val Thr Glu Gly
2630 2635 2640
Val Asp Glu Thr Gly Ser Val Thr Glu Glu Ile Ile Glu Glu Ala
2645 2650 2655
Thr Val Thr Glu Glu Val Val Glu Asp Gly Ser Val Thr Glu Glu
2660 2665 2670
Val Val Glu Asp Gly Ser Val Ile Gln Glu Val Val Glu Asp Gly
2675 2680 2685
Ser Val Thr Glu Glu Ile Val Gln Glu Asn Gly Ser Val Thr Glu
2690 2695 2700
Glu Ile Val Glu Glu Glu Gly Ser Val Asn Glu Glu Val Glu Glu
2705 2710 2715
Glu Val Ser Val Ser Gly Glu Val Asp Glu Thr Glu Tyr Val Thr
2720 2725 2730
Glu Glu Val Glu Glu Glu Gly Ser Val Val Glu Glu Ile Val Glu
2735 2740 2745
Glu Glu Gly Ser Val Ser Gly Glu Val Asp Glu Thr Glu Tyr Val
2750 2755 2760
Thr Glu Glu Val Glu Glu Glu Gly Ser Val Val Glu Glu Ile Val
2765 2770 2775
Glu Glu Glu Gly Ser Val Ser Gly Glu Val Asp Glu Thr Glu Tyr
2780 2785 2790
Val Thr Glu Glu Val Glu Glu Glu Gly Ser Val Val Glu Glu Ile
2795 2800 2805
Val Glu Glu Glu Gly Ser Val Ser Gly Glu Val Asp Glu Thr Glu
2810 2815 2820
Tyr Val Thr Glu Glu Val Glu Glu Glu Gly Ser Val Val Glu Glu
2825 2830 2835
Ile Val Glu Glu Glu Gly Ser Val Val Glu Glu Ile Val Glu Glu
2840 2845 2850
Glu Gly Ser Val Ser Glu Val Val Asp Glu Thr Glu Leu Val Asn
2855 2860 2865
Asp Glu Ile Val Glu Gln Ala Pro Phe Thr Glu Glu Val Glu Glu
2870 2875 2880
Gln Val Ser Val Asn Asp Glu Ile Ile Glu Asp Ala Ser Val Ala
2885 2890 2895
Glu Ala Val Glu Glu Ser Glu Ser Ile Thr Glu Ser Val Ser Gln
2900 2905 2910
Glu Glu Glu Thr Glu Lys Gly Phe Val Ile Glu Lys Val Glu Glu
2915 2920 2925
Thr Gly Ala Val Thr Glu Glu Ile Val Gln Asp Gly Leu Ile Thr
2930 2935 2940
Glu Glu Ile Leu Glu Glu Ser Glu Ser Val Asn Gly Glu Ile Ile
2945 2950 2955
Asn Lys Glu Ser Asp Ala Glu Glu Ile Leu Glu Thr Glu Phe Leu
2960 2965 2970
Thr Glu Glu Val Val Gly Gln Ala Gly Ser Thr Ser Glu Glu Ile
2975 2980 2985
Val Glu Glu Glu Gly Ser Val Thr Lys Glu Val Glu Glu Lys Glu
2990 2995 3000
Ser Val Thr Glu Glu Leu Val Asp Glu Gly Ser Val Thr Glu Glu
3005 3010 3015
Leu Val Asp Glu Gly Ser Val Thr Glu Glu Val Val Glu Gln Gly
3020 3025 3030
Gly Ser Ile Ala Gln Glu Ile Val Glu Glu Glu Ser Ala Thr Glu
3035 3040 3045
Glu Ile Ile Arg Asp Glu Thr Asn Val Glu Glu Val Leu Glu Lys
3050 3055 3060
Glu Gly Ser Ala Thr Glu Glu Ile Val Gln Asp Gly Ser Gly Thr
3065 3070 3075
Asn Asp Phe Val Gly Lys Gln Gly Ser Val Ile Glu Glu Val Val
3080 3085 3090
Glu Glu Glu Ile Ser Thr Thr Glu Glu Lys Leu Lys Glu Glu Ala
3095 3100 3105
Ser Ala Ile Glu Glu Phe Val Glu Glu Glu Ser Ile Arg Glu Asp
3110 3115 3120
Val Leu Glu Glu Ser Leu Val Thr Glu Asn Val Val Gly Gln Gln
3125 3130 3135
Glu Ser Val Thr Glu Glu Ile Val Asp Gly Glu Gly Ser Phe Thr
3140 3145 3150
Glu Asp Ile Val Glu Glu Glu Glu Ser Val Thr Glu Glu Ile Val
3155 3160 3165
Val Asp Glu Glu Ser Val Thr Lys Glu Ile Val Glu Asp Glu Glu
3170 3175 3180
Leu Val Thr Glu Glu Ile Val Glu Asp Glu Gly Ser Phe Thr Glu
3185 3190 3195
Glu Ile Val Glu Asp Glu Gly Ser Phe Thr Glu Glu Val Ile Glu
3200 3205 3210
Glu Arg Ser Leu Ile Glu Glu Val Glu Asp Thr Glu Thr Val Ala
3215 3220 3225
Glu Lys Glu Glu Gly Ser Val Ile Lys Glu Ile Ile Asp Glu Lys
3230 3235 3240
Ser Leu Thr Glu Lys Ile Val Glu Glu Glu Lys Ser Val Thr Glu
3245 3250 3255
Glu Val Glu Glu Lys Glu Ser Val Lys Glu Glu Val Glu Glu Gln
3260 3265 3270
Arg Leu Val Val Glu Glu Glu Gly Ser Ala Thr Glu Gly Ile Val
3275 3280 3285
Glu Asp Arg Leu Ala Thr Glu Gly Ile Val Asp Asp Ile Leu Val
3290 3295 3300
Thr Glu Glu Ile Val Glu Asp Gly Leu Ala Thr Asp Glu Phe Val
3305 3310 3315
Glu Gln Gln Gly Ser Ile Ile Glu Glu Val Leu Asp Asp Glu Gly
3320 3325 3330
Ser Val Thr Glu Glu Ile Val Glu Glu Glu Gly Ser Pro Asn Glu
3335 3340 3345
Glu Ile Val Glu Gly Val Ser Val Ile Glu Glu Asp Asp Asn Ile
3350 3355 3360
Glu Pro Val Ser Glu Glu Ile Val Glu Gly Ser Val Thr Glu Glu
3365 3370 3375
Met Ile Lys Glu Gly Leu Glu Asn Glu Val Ile Leu Asp Glu Asp
3380 3385 3390
Ser Ile Thr Glu Glu Ala Leu Glu Lys Glu Gly Ser Val Ser Glu
3395 3400 3405
Glu Ile Val Glu Glu Met Gly Ser Leu Thr Glu Glu Ile Val Asp
3410 3415 3420
Glu Glu Arg Ser Thr Ser Glu Asp Met Ile Glu Glu Gly Ser Ala
3425 3430 3435
Ser Glu Glu Ile Ile Gln Glu Glu Ser Gln Val Glu Glu Val Val
3440 3445 3450
Glu Glu Val Ser Val Ile Asp Glu Ile Val Glu Glu Asp Glu Leu
3455 3460 3465
Asp Thr Lys Glu Val Val Glu Glu Ile Glu Phe Asn Thr Glu Glu
3470 3475 3480
Val Val Glu His Lys Glu Glu Glu Gly Ser Val Ala Glu Glu Ile
3485 3490 3495
Val Gln Glu Glu Lys Glu Gly Ser Val Asn Glu Glu Ile Ile Glu
3500 3505 3510
Glu Val Gly Ser Ile Thr Glu Glu Met Val Glu Gln Asp Val Ser
3515 3520 3525
Asp Asn Glu Glu Ile Val Glu Glu Arg Ser Val Ile Glu Glu Ala
3530 3535 3540
Glu Glu Asn Val Trp Ile Glu Lys Glu Val Glu Glu Glu Gly Leu
3545 3550 3555
Asp Asn Glu Glu Val Ile Asp Glu Glu Asp Ser Val Ser Glu Gln
3560 3565 3570
Ala Glu Glu Glu Val Tyr Ile Asn Glu Glu Ile Leu Lys Glu Ser
3575 3580 3585
Ser Asp Val Glu Asp Val Lys Val Glu Asn Glu Leu Met Asn Glu
3590 3595 3600
Glu Val Asn Glu Glu Thr Gln Ser Val Ala Glu Asn Asn Glu Glu
3605 3610 3615
Asp Lys Glu Leu Asp Asn Tyr Val Val Glu Glu Thr Glu Ser Val
3620 3625 3630
Thr Glu Glu Val Val Val Asp Glu Val Pro Asn Ser Lys Glu Val
3635 3640 3645
Gln Glu Ile Glu Ser Ile Ile Glu Glu Ile Val Glu Asp Gly Leu
3650 3655 3660
Thr Thr Asp Asp Leu Val Gly Gln Gln Gly Ser Val Ile Glu Glu
3665 3670 3675
Val Val Glu Glu Val Gly Ser Asp Ser Glu Glu Ile Val Glu Glu
3680 3685 3690
Ala Ser Ile Thr Glu Glu Val Glu Lys Lys Glu Ser Val Thr Glu
3695 3700 3705
Asp Ile Leu Val Glu Glu Ser Val Thr Gly Asp Ile Leu Val Glu
3710 3715 3720
Gly Ser Val Thr Glu Glu Val Val Gly Glu Glu Lys Leu Val Ser
3725 3730 3735
Glu Glu Ile Val Thr Glu Glu Gly Ser Val Ala Gln Glu Ile Val
3740 3745 3750
Glu Glu Asp Ala Pro Ala Thr Glu Glu Ile Asp Glu Ile Glu Ser
3755 3760 3765
Val Thr Glu Glu Val Val Glu Glu Glu Gly Pro Val Asp Glu Glu
3770 3775 3780
Ile Val Gln Glu Glu Gly Ser Val Thr Glu Glu Ile Ile Gln Gly
3785 3790 3795
Glu Ser Lys Val Glu Glu Val Val Glu Glu Gln Gly Ser Glu Asn
3800 3805 3810
Glu Glu Ile Phe Val Glu Glu Val Ser Ala Ser Gln Glu Ile Val
3815 3820 3825
Gln Asn Glu Ser Gly Thr Glu Glu Ile Leu Glu Lys Val Ser Ala
3830 3835 3840
Ser Gln Glu Ile Val Gln Asp Gly Ser Val Thr Glu Gln Ile Ile
3845 3850 3855
Glu Glu Gln Lys Pro Val Thr Glu Glu Val Val Asn Glu Glu Glu
3860 3865 3870
Ser Ile Thr His Glu Ile Ile Gln Glu Glu Ser His Val Glu Lys
3875 3880 3885
Val Val Gln Gln Gly Ser Val Ala Glu Glu Val Val Glu Asn Pro
3890 3895 3900
Val Ser Val Thr Glu Glu Ile Val Glu Lys Glu Gly Ser Val Thr
3905 3910 3915
Glu Asp Ile Gly Gln Glu Gly Tyr Val Ala Glu Glu Ile Val Glu
3920 3925 3930
Glu Glu Glu Phe Asp Asn Glu Glu Ile Leu Glu Glu Glu Ser Val
3935 3940 3945
Ala Glu Glu Phe Val Glu Glu Gly Phe Asp Asn Glu Glu Ile Phe
3950 3955 3960
Val Glu Gln Ile Ser Asp Ser Glu Ile Val Lys Glu Glu Asn Ser
3965 3970 3975
Val Asn Glu Glu Val Leu Glu Glu Glu Gly Ser Tyr Thr Glu Glu
3980 3985 3990
Ile Leu Glu Glu Glu Gly Ser Tyr Thr Glu Glu Ile Leu Glu Glu
3995 4000 4005
Glu Gly Ser Phe Thr Glu Glu Ile Leu Glu Glu Glu Gly Ser Tyr
4010 4015 4020
Asn Glu Glu Ile Leu Glu Glu Glu Gly Ser Tyr Asn Glu Glu Ile
4025 4030 4035
Leu Glu Glu Glu Gly Ser Tyr Asn Glu Glu Ile Leu Glu Glu Glu
4040 4045 4050
Gly Ser Tyr Asn Glu Glu Ile Leu Glu Glu Glu Gly Ser Ala Thr
4055 4060 4065
Asp Tyr Phe Val Gly Gln Gly Ser Asp Asn Glu Glu Ile Ile Glu
4070 4075 4080
Glu Gly Ser Ala Thr Asp Tyr Phe Val Gly Gln Gly Ser Asp Asn
4085 4090 4095
Glu Glu Ile Ile Glu Glu Gly Ser Ala Thr Asp Tyr Phe Val Gly
4100 4105 4110
Gln Gly Ser Ile Ile Glu Glu Val Leu Glu Glu Glu Gly Leu Asp
4115 4120 4125
Thr Glu Lys Val Phe Glu Asn Glu Gly Ser Ala Thr Glu Phe Glu
4130 4135 4140
Glu Thr Glu Ser Phe Thr Glu Val Val Glu Glu Thr Glu Ser Val
4145 4150 4155
Asn Glu Asn Ile Leu Glu Glu Thr Ser Ile Asn Glu Val Gln Lys
4160 4165 4170
Ile Glu Ser Ile Thr Glu Asp Ile Lys Glu Gln Leu Val Pro Glu
4175 4180 4185
Glu Ile Lys Glu Glu Gln Leu Asp Ser Glu Glu Ile Lys Glu Glu
4190 4195 4200
Gln Leu Asp Ser Glu Glu Ile Lys Glu Glu Gln Leu Val Pro Glu
4205 4210 4215
Glu Ile Lys Glu Glu Gln Leu Asp Ser Glu Glu Ile Lys Glu Glu
4220 4225 4230
Gln Leu Asp Ser Glu Glu Ile Lys Glu Glu Gln Leu Asp Ser Glu
4235 4240 4245
Glu Ile Lys Glu Glu Gln Leu Asp Ser Glu Glu Ile Lys Glu Glu
4250 4255 4260
Gln Leu Val Pro Glu Glu Ile Lys Glu Glu Gln Leu Asp Ser Glu
4265 4270 4275
Glu Ile Lys Glu Glu Gln Leu Val Pro Glu Glu Ile Lys Glu Glu
4280 4285 4290
Gln Leu Asp Ser Glu Glu Ile Lys Glu Glu Gln Leu Asp Ser Glu
4295 4300 4305
Glu Ile Lys Glu Glu Gln Leu Asp Ser Glu Glu Ile Lys Glu Glu
4310 4315 4320
Gln Leu Asp Ser Glu Glu Ile Lys Glu Gln Lys Gly Ser Val Asn
4325 4330 4335
Glu Glu Val Val Glu Glu Glu Gly Ser Val Thr Glu Glu Ile Lys
4340 4345 4350
Glu Gln Glu Glu Ser Val Asn Glu Glu Val Leu Glu Glu Val Glu
4355 4360 4365
Glu Thr Glu Ser Ile Lys Glu Glu Ile Val Glu Gly Gly Ile Ala
4370 4375 4380
Thr Gln Glu Ile Ile Glu Glu Glu Ser Asp Thr Lys Glu Val Val
4385 4390 4395
Glu Glu Glu Val Ile Asp Ser Glu Lys Leu Val Asp Ala Gly Ser
4400 4405 4410
Val Thr Gly Glu Val Met Pro Glu Glu Val Ser Val Thr Asp Glu
4415 4420 4425
Val Val Glu Glu Gly Ser Thr Thr Glu Glu Val Leu Glu Glu Gln
4430 4435 4440
Lys Ser Val Asn Glu Glu Val Val Glu Asp Gly Leu Thr Ile Asp
4445 4450 4455
Asp Phe Val Gly Leu Gln Gly Ser Thr Thr Glu Glu Val Val Glu
4460 4465 4470
Glu Asp Gly Ser Ala Ile Glu Lys Ile Leu Glu Glu Glu Thr Ala
4475 4480 4485
Thr Glu Glu Ile Val Glu Lys Gln Val Ser Val Thr Glu Asp Ile
4490 4495 4500
Val Glu Lys Glu Gly Ser Val Asn Glu Glu Ile Ile Glu Glu Ala
4505 4510 4515
Ser Val Ala Glu Glu Ile Ile Gln Gly Gly Ser Phe Thr Glu Glu
4520 4525 4530
Ile Val Gly Gln Glu Glu Ser Ala Thr Glu Glu Val Ile Asp Glu
4535 4540 4545
Glu Gly Leu Ile Ser Asn Glu Ile Glu Glu Glu Glu Glu Lys Ser
4550 4555 4560
Val Thr Glu Glu Met Ile Glu Glu Val Glu Glu Val Ser Val Asp
4565 4570 4575
Asp Glu Val Glu Glu Val Ser Val Ala Glu Glu Ile Val Glu Glu
4580 4585 4590
Glu Leu Val Asp Asp Glu Ile Leu Pro Glu Glu Leu Ser Ala Thr
4595 4600 4605
Glu Asp Val Ile Glu Glu Val Arg Ser Val Thr Asp Glu Ile Val
4610 4615 4620
Gln Glu Glu Ser Val Cys Glu Glu Ile Leu Glu Gln Glu Val Ser
4625 4630 4635
Ala Ser Glu Glu Tyr Val Asp Asp Lys Ser Val Thr Asp Asp Phe
4640 4645 4650
Val Gly His Glu Arg Ser Val Ile Gln Asp Val Glu Asn Thr Glu
4655 4660 4665
Ser Val Thr Glu Glu Ile Ala Glu Val Asp Lys Ser Val Ile Glu
4670 4675 4680
Glu Ala Val Glu Lys Gln Gly Ser Val Thr Glu Glu Lys Val Gln
4685 4690 4695
Glu Gly Val Ser Ala Ile Glu Glu Ile Glu Glu Leu Glu Ser Val
4700 4705 4710
Thr Glu Glu Ile Ala Glu Glu Asp Lys Ser Val Ile Glu Glu Ala
4715 4720 4725
Val Glu Lys Gln Gly Ser Val Thr Glu Glu Ile Val Glu Glu Glu
4730 4735 4740
Glu Leu Asp Thr Glu Glu Val Leu Glu Asp Lys Ser Val Thr Gly
4745 4750 4755
Asp Val Val Glu Gln Glu Gly Ser Gly Lys Asp Glu Ser Glu Ala
4760 4765 4770
Lys Glu Ser Phe Thr Glu Glu Val Asp Glu Leu Lys Ser Val Lys
4775 4780 4785
Glu Glu Asp Gln Glu Thr Glu Tyr Ile Ser Arg Glu Ile Glu Glu
4790 4795 4800
Glu Ser Ala Thr Glu Gln His Ser Glu Gln Glu Leu Ser Ile Asn
4805 4810 4815
Lys Glu Val Val Glu Thr Glu Ser Leu Thr Lys Asp Ile Glu Glu
4820 4825 4830
Glu Lys Ser Thr Thr Gln Glu Ile Leu Glu Glu Thr Gln Ser Val
4835 4840 4845
Asn Glu Glu Ile Val Glu Glu Glu Arg Asp Thr Asp Glu Val Leu
4850 4855 4860
Lys Glu Lys Val Ser Pro Ser Glu Glu Val Ile Glu Glu Gln Ala
4865 4870 4875
Ser Thr Thr Glu Glu Phe Val Glu Glu Arg Ser Ser Thr Asp Glu
4880 4885 4890
Ile Val Glu Val Glu Asp Leu Phe Thr Glu Glu Val Lys Glu Arg
4895 4900 4905
Glu Gly Ser Val Thr Glu Glu Ile Val Glu Glu Gly Ser Asp Thr
4910 4915 4920
Gly Glu Ile Val Glu Glu Glu Gly Ser Asp Thr Glu Glu Ile Leu
4925 4930 4935
Glu Glu Gly Ser Phe Asn Glu Glu Ile Val Glu Glu Glu Gly Ser
4940 4945 4950
Ile Thr Glu Glu Ile Leu Gln Gly Ser Val Thr Glu Glu Ile Leu
4955 4960 4965
Gln Gly Ser Val Thr Glu Glu Phe Val Gly Gln Gln Gly Ser Val
4970 4975 4980
Ile Glu Glu Ile Val Glu Thr Glu Ser Ala Ile Glu Glu Arg Val
4985 4990 4995
Glu Glu Glu Ser Ala Thr Glu Glu Val Asp Glu Arg Glu Ser Val
5000 5005 5010
Thr Glu Val Val Glu Glu Glu Val Ser Ser Ser Asp Glu Val Val
5015 5020 5025
Glu Gly Ser Ile Glu Glu Val Ile Glu Asn Glu Gly Ser Val Thr
5030 5035 5040
Glu Glu Ile Leu Glu His Glu Val Ser Ala Asp Glu Asn Phe Val
5045 5050 5055
Gly Gln Ala Val Ser Val Ile Glu Glu Val Glu Gly Thr Glu Ser
5060 5065 5070
Val Thr Glu Glu Val Val Glu Glu Thr Glu Ser Val Ser Glu Glu
5075 5080 5085
Ile Val Glu Val Ser Pro Thr Glu Asn Val Val Gln Gln Thr Asp
5090 5095 5100
Ser Val Ile Glu Glu Val Val Glu Gln Lys Glu Gly Ser Phe Asn
5105 5110 5115
Glu Glu Ile Asp Ile Arg Glu Leu Gly Asp Asp Gly Val Glu Glu
5120 5125 5130
Arg Glu Lys Ile Ser Thr Glu Glu Val Val Gly Gln Asp Lys Ser
5135 5140 5145
Ala Thr Gly Asp Val Glu Glu Val Ser Ser Thr Glu Asp Glu Glu
5150 5155 5160
Glu Val Ser Ser Thr Glu Gly Leu Glu Glu Val Ser Ser Thr Glu
5165 5170 5175
Gly Leu Glu Glu Val Ser Asn Thr Glu Asp Val Glu Glu Val Ser
5180 5185 5190
Ser Thr Glu Asp Val Glu Glu Gly Ser Val Ala Glu Asn Val Lys
5195 5200 5205
Glu Thr Lys Ser Ile Thr Glu Glu Val Ser Val Glu Glu Asp Ile
5210 5215 5220
Ile Thr Asp Lys Val Ser Val Glu Gln Glu Val Met Ala Glu Ala
5225 5230 5235
Ser Val Glu Glu Asn Ile Leu Thr Glu Val Pro Val Glu Glu Glu
5240 5245 5250
Ile Met Thr Glu Lys Leu Ser Val Glu Asp Lys Ala Leu Asn Glu
5255 5260 5265
Lys Ile Met Ser Glu Glu Glu Ile Val Ile Glu Asp Gly Asn Val
5270 5275 5280
His Glu Val Val Pro Ala Glu Val Ser Val Thr Glu Glu Ile Pro
5285 5290 5295
Gly Val Glu Glu Thr Thr Asn Asn Glu Ser His Val Lys Gly Glu
5300 5305 5310
Asn Val Val Asn Glu Val Val Val Asp Asp Asn Ser Val Asn Asp
5315 5320 5325
Glu Ile Gln Phe Asp Asp Asp Ser Ser Ile Glu Ile Tyr Thr Val
5330 5335 5340
Asp Ser Lys Asp Val Phe His Lys Glu Glu Asn Tyr Asp Ser Phe
5345 5350 5355
Arg Glu Glu Val Arg Ser Asp Glu Asn Ile His Ile Phe Arg Lys
5360 5365 5370
Lys Asn Glu Asn Phe Val Lys Lys Ile Glu Asn Glu Lys Ser Ser
5375 5380 5385
Val Gly His Val Pro Thr Glu Tyr Thr Ser Lys Glu Asn Ile Ala
5390 5395 5400
Glu Glu Val Pro Ser His Ile Met Phe Lys Glu Asn Val Thr Glu
5405 5410 5415
Glu Val Pro Lys Glu Val Lys Tyr Glu Glu Asn Thr Val Glu Glu
5420 5425 5430
Val Phe Glu Glu Val Thr Ser Lys Glu Asn Ile Ile Glu Glu Ala
5435 5440 5445
Pro Gly Asp Ile Asn Ser Glu Glu Asn Ile Ile Glu Glu Val Pro
5450 5455 5460
Glu Val Val Thr Ser Glu Glu Ile Val Val Gln Asn Asp Val Asn
5465 5470 5475
Asn Ile Asn Thr Asn Ile Asp His Met Phe Asp Phe Asp Leu Asp
5480 5485 5490
Asp Ile Leu Lys Ile Pro Glu Ala Gln Arg Lys Leu Asn Lys Leu
5495 5500 5505
Arg Thr Leu Val Asp Val His Leu Asp Val Ile Glu Lys Met Gln
5510 5515 5520
Arg Asp Glu Trp Lys Lys Asn Lys Arg Asp Phe Leu Tyr Ile Cys
5525 5530 5535
Leu Lys Glu Ile Asn Lys Leu Ser Glu Asp Thr Leu Met Lys Phe
5540 5545 5550
Tyr Gly Ser Asp Ser Asn Lys Ser Ala Asn Asp Asn Asp Thr Val
5555 5560 5565
Met Val Ile Lys Ile Leu Lys Asp Lys Trp Gly Thr Gly Arg Ile
5570 5575 5580
Val Asp Thr Ile Ala Asn Ser Leu Asn Lys Ser Tyr Asn Ser Leu
5585 5590 5595
Tyr His Asn Leu Tyr Ile Glu Met Glu Lys Asp Leu Leu Ile Asn
5600 5605 5610
Lys Thr Glu Thr Phe Asn Lys Trp Ser Lys Gln His Trp Asn Lys
5615 5620 5625
Leu Asp Asn Trp Lys Glu Glu Lys Trp Phe Lys Leu Phe Lys Arg
5630 5635 5640
Asp Leu Lys Ile Asp Met Arg Asn Thr Tyr Glu Ser Asp Gln Asn
5645 5650 5655
Asp Glu Glu Asn Asn Glu Glu Ser Met Asn Glu Leu Ser Asp Glu
5660 5665 5670
Leu Ile Lys Asn Asn Thr Ser Asp Asn Met Arg Asn Glu Gln Lys
5675 5680 5685
Thr Leu Glu Lys Asn Lys Glu Tyr Ser Asn Leu Ser Lys Asp Leu
5690 5695 5700
Gly Leu Ile Glu Lys Gln Lys Ile Ile Trp Lys Ser Trp Ile Val
5705 5710 5715
Lys Asn Val Asn Asn Ile Glu Asn Trp Phe Asp Glu Met Trp Phe
5720 5725 5730
Lys Asn Val Val Asn Glu Leu Lys Glu Lys Asn Asp Val Ser Asn
5735 5740 5745
Val Leu Gln Glu Asn Ala Ser Glu Ala Ser Val Glu Asn Tyr Ile
5750 5755 5760
Ser Asp Val Glu Asp Ser Lys Asp Met Thr Asn Ser Ile Asn Asp
5765 5770 5775
Ser Glu Lys Ser Lys Ile Val Ala Ser Ser Ser Lys Thr Thr Asn
5780 5785 5790
Glu Glu Tyr Ile Ile Leu Ser Arg Lys Asp Leu Ile Tyr Asn Ile
5795 5800 5805
Ile Val Met Val His Met Met Val Leu Asp Gln Phe Lys Tyr Asp
5810 5815 5820
Glu Leu Lys Tyr Ala Lys Lys Arg Phe Leu Asn Arg Ser Ile Asp
5825 5830 5835
Lys Phe Ile Lys Glu Lys Lys Ile Lys Asp Lys Glu Thr Val Leu
5840 5845 5850
Asp Tyr Tyr Ile Asp Asp Ile Ile Lys Arg Ile Val Glu Asp Thr
5855 5860 5865
Ser His Val Asn Asn Ile Lys Glu Lys Ala Ile Asp His Tyr Thr
5870 5875 5880
Ser His Asp Trp Phe Arg Leu Leu Arg Gln Gly Asn Lys Ala Gln
5885 5890 5895
Asn Ser Ile Ser Gln Glu Val Asp Ile Leu Thr Glu Lys Tyr Lys
5900 5905 5910
Lys Leu Ile Ser Glu Glu Asp Asn Lys Lys Glu Asn Asn Asn Asn
5915 5920 5925
Asn Asp Asp Glu Val Lys Pro Glu Leu Lys Asp Asn Ile Lys Cys
5930 5935 5940
Glu Glu Asn Val Ser Phe Asn Ile Leu Arg Arg Ser Asn Lys Lys
5945 5950 5955
Asp Gln Leu Pro Leu Glu Glu Lys Lys Asn Lys Asn Gly Asp Leu
5960 5965 5970
Asn Asn Thr Leu Thr Glu Ser Asp Gly Lys Lys Ile Asn Ile Asn
5975 5980 5985
Glu Ala Ile Glu Glu Ser Lys Asn Gly Asn Glu Asp Lys Asn Ser
5990 5995 6000
Gly Asn Met Glu Lys Ser Arg Lys Pro Arg Asp Arg Arg Thr Glu
6005 6010 6015
Arg Lys Glu Lys Asp Gln Asp Leu Arg Val Gln Leu Leu Gln Asp
6020 6025 6030
Tyr Glu Asn Ile Phe Glu Gln Ile Gln Asn Met Glu Asn Gln Asn
6035 6040 6045
Lys Asp Lys Asn Lys Lys Glu Thr Lys Asn Ile Leu Lys Thr Ser
6050 6055 6060
Ile Asp Leu Asp Lys Asn Leu Leu Arg Glu Tyr Lys Lys Glu Lys
6065 6070 6075
Asn Ile Ile Asn Gln Ser Glu Lys Glu Phe Ser Val Asn Glu Asn
6080 6085 6090
<210> 59
<211> 994
<212> PRT
<213> 恶性疟原虫
<400> 59
Met Lys Phe Phe Ile Pro Tyr Val Tyr Ile Ile Cys Val Ile Phe Ile
1 5 10 15
Ile Asn Val Ile Arg Thr Arg Gly Glu Glu Asp Asp Asp Asn Asn Asn
20 25 30
Ile Ser Gly Lys Ser Ile Leu Gly Thr Ser His Asn Asn Ile Ser Asn
35 40 45
Ile Asp Leu Ser Ser Ile Pro Asn Leu Asp Ser Asn Ile His Ala Ser
50 55 60
Phe Ser Ser Asp Thr Lys Glu Trp Ser Pro Asn Asn Leu Thr Ser Lys
65 70 75 80
Lys Lys Lys Lys Lys Lys Glu Ile Arg Pro Lys Asp Ile Met Ser Asn
85 90 95
Ser Asp Ser Ser Asn Thr Ser Ser Ile Asn Lys Gln Asn Asn Asn Gln
100 105 110
Ile Lys Ser Val Leu Leu Lys Glu Asn Lys Gly Val Lys Ile Thr Gly
115 120 125
Pro Cys Asn Val Asn Leu Ser Ile Phe Leu Val Pro His Ile Tyr Ile
130 135 140
Asp Val Glu Thr Lys Tyr Asn Asn Ile Glu Leu Lys Tyr Glu Leu Asp
145 150 155 160
Glu Phe Ser Asp Ser Ile Lys Phe Lys Asp Thr Thr Thr Glu Leu Arg
165 170 175
Thr Ser Asp Asp Thr Leu Met Asn Thr Asn Phe Asn Val Gly Val Ser
180 185 190
Arg Asp Thr Leu Asp Lys Asp Arg Leu Tyr Asn Ile Cys Ala Glu Asn
195 200 205
Lys Thr Phe Lys Phe Val Val Tyr Ile Lys Asp Asn Ile Leu Thr Leu
210 215 220
Lys Trp Lys Val Tyr Glu Thr Gly Val Thr Asn Asn Lys Val Asp Ile
225 230 235 240
Arg Gln Tyr Lys Met Lys Glu Leu Thr Arg Pro Ile Thr Thr Ile Gln
245 250 255
Ile His Ser Val Ser Glu Asn Lys Asp Thr His Leu Leu Glu Ser Lys
260 265 270
Asn Tyr Val Ile Lys Thr Asp Ile Pro Glu Thr Cys Asp Val Met Ala
275 280 285
Thr Asn Cys Phe Leu Ser Gly Asn Ile Asn Ile Glu Lys Cys Leu Glu
290 295 300
Cys Thr Leu Leu Val Gln Asn Asn Asp Thr Ser Ser Glu Cys Phe Thr
305 310 315 320
Tyr Val Ser Asn Asp Val Arg Glu Asn Phe Asn Gln Ile Lys Ala Glu
325 330 335
Ala Glu Asp Asp Glu Asn Phe Arg Asn Tyr His Leu Thr Asp Thr Ile
340 345 350
Asn Asn Ile Leu Lys Arg Ile Tyr Lys Ile Asn Lys Asn Glu Gly Lys
355 360 365
Lys Glu Leu Ile Thr Leu Glu Glu Leu Asp Asn Phe Leu Lys Glu Ser
370 375 380
Ile Thr Asp Tyr Cys Lys Ile Leu Arg Glu Ile Asp Thr Asn Gly Thr
385 390 395 400
Leu Val Asn His Glu Leu Gly Asn Asn Val Asp Val Phe Asn Asn Leu
405 410 415
Ile Arg Leu Leu Lys Leu His Lys Asn Glu Ser Ile Ser Thr Leu His
420 425 430
Asn Lys Leu Arg Asn Ser Ala Ile Cys Met Lys Tyr Pro Asp Lys Trp
435 440 445
Ile Glu Lys Lys Thr Gly Leu Ile Leu Pro Asn Val Val Asn Asn Asn
450 455 460
Ile Ile Tyr Asn Asn Lys Tyr Glu Lys Leu Asn Glu Glu Lys Lys Arg
465 470 475 480
Lys Ile Tyr Asp Asn Lys Asp Asp Ser Lys Ile Ser Asp Ile Ile Asn
485 490 495
Ile Lys Lys Tyr Ile Phe Thr Asn Asn Thr Leu Lys Tyr Phe Asn Asn
500 505 510
Asp Lys Gln Phe Cys Asn Ser Ser Phe Cys Asn Arg Leu Lys Asp Glu
515 520 525
Asn Asn Cys Ile Ser Lys Ile Gln Ile Glu Asp Gln Gly Asn Cys Ala
530 535 540
Ile Ser Trp Ile Phe Ala Ser Lys Tyr Tyr Leu Glu Thr Leu Lys Cys
545 550 555 560
Met Lys Gly Tyr Glu Pro His Ala Ile Ser Ala Leu Tyr Ile Ala Asn
565 570 575
Cys Ser Lys Arg Lys His Lys Asn Arg Cys Asn Val Gly Ser Asn Pro
580 585 590
Leu Glu Phe Leu Gln Ile Ile Glu Glu Asn Gln Phe Leu Pro Met Asp
595 600 605
Thr Asn Tyr Leu Tyr Ser Tyr Thr Lys Val Gly Asn Asp Cys Pro Asp
610 615 620
Glu Glu Lys Asn Trp Val Asn Leu Leu Lys His Thr Arg Met Leu Asn
625 630 635 640
Tyr Asn Asn Lys His Arg Ser Thr Leu Ser Thr Lys Ala Tyr Arg Ala
645 650 655
Tyr Glu Ser Glu His Phe Lys Asp Lys Met Asp Thr Phe Ile Lys Leu
660 665 670
Ile Lys Asp Glu Ile Met Asn Asn Gly Ser Val Ile Ala Tyr Val Lys
675 680 685
Ala Glu Asn Val Leu Gly Tyr Glu Leu Asn Gly Lys Asn Val Gln Asn
690 695 700
Leu Cys Gly Asp Lys Thr Pro Asp His Ala Val Asn Ile Val Gly Tyr
705 710 715 720
Gly Asn Tyr Ile Asn Asp Glu Asp Glu Lys Lys Ser Tyr Trp Ile Val
725 730 735
Arg Asn Ser Trp Gly Lys Tyr Trp Gly Asp Glu Gly Tyr Phe Lys Val
740 745 750
Asp Met Tyr Gly Pro Ser Thr Cys Glu Asp Asn Phe Ile His Thr Val
755 760 765
Val Val Phe Asn Ile Asn Met Pro Lys Ser Lys Lys Ser Pro Val Lys
770 775 780
Ile Thr Phe Pro Leu Tyr Asn Tyr Tyr Leu Lys Tyr Ser Pro Asp Phe
785 790 795 800
Tyr His Asn Leu Tyr Tyr Lys Asn Phe Asn Ser Lys Lys Ser Met Lys
805 810 815
Leu Val Asn Ala Ser Asp Glu His Lys Asn Ile Tyr Ser Gln Glu Asp
820 825 830
Lys Val Asn His Lys Lys Gly Ser Lys Ile Leu Asn Ser Glu Val Thr
835 840 845
Thr Ser Leu Leu Ser Gln Glu Ile Ser Gln Arg Arg Gly Glu Asp Asp
850 855 860
Asp Ile Asp Thr Leu Ile Gly Asp Ser Pro Asp Ile Asn Glu Gln Glu
865 870 875 880
Lys Asn Ile Lys Asp Glu Phe Asn Lys Ser Ser Ile Thr His Asn Ser
885 890 895
Val Ser Ser Ser Asn Ile Thr Lys Ser Asn Lys Asn Thr Asn Lys Val
900 905 910
Lys Ile Tyr His Ile Ile Lys His Val Lys Asn Thr Lys Ile Lys Ile
915 920 925
Gly Phe Val Lys Tyr Asp Asn Tyr Asn Thr Ile Gly Thr Asn His Thr
930 935 940
Cys Ser Arg Ser Tyr Ser Glu Asp Gln Glu Lys His Glu Gly Cys Ile
945 950 955 960
Lys Phe Cys Glu Leu His Trp Asn Glu Cys Lys Asp Lys Thr Ser Pro
965 970 975
Gly Tyr Cys Leu Thr Lys Leu Lys Gly Ser Asn Glu Cys Phe Phe Cys
980 985 990
Tyr Val
<210> 60
<211> 1105
<212> PRT
<213> 恶性疟原虫
<400> 60
Met Lys Phe His Ile Ser Phe Phe Leu Ile Leu Tyr Ile Val Phe Phe
1 5 10 15
Lys Asn Thr Ile Lys Ser Glu Thr Thr Thr Asp Glu Ser Ala Thr Gly
20 25 30
Ser Leu Ser Ser Asp Gly Ser Arg Val Thr Thr Gln Ala Arg Ile Glu
35 40 45
Lys Pro Lys Gln Gln Pro Thr Leu Pro Thr Leu Ala Gln Glu Thr Gln
50 55 60
Pro Gln Gln Gln Gln Gln Gln Lys Glu Val Gly Ser Gly Ile Gly Ala
65 70 75 80
Glu Gln Lys Val Glu Ser Ala Arg Pro Gly Ala Glu Val Ser Gln Ser
85 90 95
Asp Val Glu Arg Ala Gly Arg Ser Ser Gly Thr Gly Gly Ser Val Gly
100 105 110
Thr Lys Ile Ser Pro Gly Ser Gln Gly Gln Gly Lys Val Ala Gly Pro
115 120 125
Gln Leu Pro Arg Leu Pro Gln Leu Pro Gln Ser Phe Glu Gln Ser Arg
130 135 140
Asn Gln Gln Ser Ser Pro Val Thr Pro Lys Arg Asn Gly Ile Ser Pro
145 150 155 160
Thr Asn Ala Lys Ser Pro Glu Ser Val Leu Pro Pro Ala Gln Ser Phe
165 170 175
Thr Asn Leu Asn Lys Ser Thr Ile Pro His Thr Ile Pro Ile Lys Ser
180 185 190
Ser Phe Leu Lys Tyr Tyr Lys Gly Val Lys Ile Thr Gly Ser Cys Gly
195 200 205
Val Gln Phe Gln Leu Val Ile Val Pro His Leu Phe Ile Tyr Val Glu
210 215 220
Thr Lys Glu Asn Asn Ile Gln Leu Glu Pro Arg Phe Met Lys Leu Asn
225 230 235 240
Glu Arg Ile Asp Phe Glu Lys Asp Lys Ser Asn Leu Lys Asn Lys Cys
245 250 255
Asp Val Asn Lys Lys Gln Ser Phe Lys Phe Ile Leu Tyr Leu Gln His
260 265 270
Asp Leu Ile Thr Ile Lys Trp Lys Val Tyr Glu Glu Lys Pro Asp Thr
275 280 285
Thr Thr Arg Ile Ala Pro Gly Gln Val Asp Leu Asn Val Asp Val Lys
290 295 300
Arg Tyr Lys Leu Pro Lys Leu Asp Gln Pro Val Ile Ser Ile Gln Ile
305 310 315 320
His Ser Leu Ala Gln Asp Gly Glu Thr Tyr Leu Met Glu Ser Lys Asp
325 330 335
Tyr Asn Leu Glu Asp Gln Ile Pro Glu Lys Cys Glu Ala Ile Ala Ser
340 345 350
Asp Cys Phe Leu Ser Gly Asn Val Asp Ile Glu Lys Cys Leu Gln Cys
355 360 365
Thr Leu Leu Val Ile Lys Ala Asp Lys Asn Asp Glu Cys Leu Lys Tyr
370 375 380
Val Ser Lys Asn Val Lys Asp Arg Phe Glu Glu Ile Leu Thr Lys Gly
385 390 395 400
Glu Asp Asp Ala Asp Ser Asp Glu Tyr Asp Phe Ile Ala Pro Ala Asn
405 410 415
Tyr Ile Leu Lys Asn Ile Tyr Lys Lys Asn Asp Thr Asn Gly Lys Lys
420 425 430
Glu Leu Leu His Phe Lys Asp Ile Asn Asn Asn Leu Lys Leu Glu Leu
435 440 445
Ile Asn Tyr Cys Asn Leu Leu Lys Asp Asn Asp Val Ser Gly Ile Leu
450 455 460
Thr Tyr Glu Lys Leu Gly Asn Val Gln Asp Ile Phe Asn Asn Leu Thr
465 470 475 480
Lys Leu Leu Glu Glu His Lys Glu Glu Asn Asn Tyr Val Leu Tyr His
485 490 495
Lys Met Lys Asn Glu Val Leu Cys Leu Lys Asn Ala Asn Asp Trp Met
500 505 510
Lys Asn Lys Thr Gly Leu Val Leu Pro Gln Leu Lys Tyr Ser Leu Asn
515 520 525
Lys Phe Asn Lys Asn Lys Glu Asn Tyr Ile Lys Glu Asn Ile Phe Glu
530 535 540
Glu Asp Glu Asn Gly Ile Val Asp Leu Thr Lys Phe Pro Val Asp Thr
545 550 555 560
Ser Tyr Ser Ser Tyr Asn Tyr Ala Asp Ser Leu Tyr Cys Asn Arg Glu
565 570 575
Tyr Cys Asn Arg Leu Lys Asp His Asn Asn Cys Ile Ser Lys Ile Asn
580 585 590
Val Glu Asp Gln Lys Asn Cys Ala Leu Ser Trp Ala Phe Ala Ser Ile
595 600 605
Tyr His Leu Glu Thr Ile Lys Cys Met Lys Gly Tyr Glu Pro Leu Asn
610 615 620
Ala Ser Val Leu Tyr Val Thr Asn Cys Leu Lys Asn Lys Asn Asn Asp
625 630 635 640
Val Cys Thr Glu Gly Ser Asn Pro Leu Val Phe Leu Glu Thr Ile Glu
645 650 655
Glu Lys Gly Phe Leu Pro Thr Glu Ser Asn Tyr Pro Tyr Asp Gln Ser
660 665 670
Lys Val Gly Asp Val Cys Pro Gln Val Gln Asn Asp Trp Asp Asn Val
675 680 685
Phe Glu Asn Thr Lys Val Leu Glu Tyr Asn Asn Ala Pro Phe Ser Val
690 695 700
Gly Thr Lys Gly Tyr Ile Ala Tyr Glu Ser Glu Val Phe Gln Lys Asp
705 710 715 720
Ile Asp Ser Phe Val Lys Leu Ile Lys Asp Glu Ile Met Asn Lys Gly
725 730 735
Ser Val Ile Ala Tyr Val Lys Ala Lys Asn Val Leu Gly Tyr Glu Leu
740 745 750
Asn Gly Lys Lys Val Gln Asn Leu Cys Gly Asp Lys Lys Pro Asp His
755 760 765
Ala Val Asn Ile Val Gly Tyr Gly Asn Tyr Ile Asn Asn Lys Gly Glu
770 775 780
Lys Lys Ser Tyr Trp Ile Val Arg Asn Ser Trp Gly Lys Tyr Trp Gly
785 790 795 800
Asp Asp Gly Tyr Phe Lys Val Asp Met Tyr Gly Pro Pro Thr Cys Glu
805 810 815
Asp Asn Phe Ile His Ser Val Val Val Phe Asn Val Glu Val Pro Val
820 825 830
Asn Glu Asn Phe Asp Lys Lys Glu His Asp Ile Tyr Lys Ser Tyr Leu
835 840 845
Lys Asn Ser Pro Asp Phe Tyr His Asn Ile Tyr Tyr Lys Asn Tyr Asn
850 855 860
Phe Glu Asn Tyr Val Ser Pro Ile Ser Thr Trp Ser Glu Val Leu His
865 870 875 880
Asn Thr Leu Tyr Asn Asn Asn Leu Ile Trp Gly Gln Glu Thr Thr Asp
885 890 895
Pro Ile Gly Glu Gly Lys Leu Pro Ala Ser Glu Ala Gly His Leu Arg
900 905 910
Gly Glu Gly Lys Gly Asn Ser Glu Glu Asn Gln Gly Gln Arg Ser Asn
915 920 925
Ala Asn Gly Ala Ile Ser Ser Asn Gln Ser Thr Gly Gly Lys Ile Thr
930 935 940
Lys Gln Gly Glu Ser Lys Asp Asp Gly Val Ala Leu Pro Val Ser Thr
945 950 955 960
Asp Gly Lys Pro Asn Thr Ser Ser Ser Val Val Asp Thr Asn Asp Gln
965 970 975
Arg Ser Leu Pro Asn Pro Arg Ala Thr Ser Leu Gln Pro Pro Ser Val
980 985 990
Gln Ile Pro Asn His Glu Gly Thr Ser Ala Pro Gly Asn Ser Arg Thr
995 1000 1005
Pro Ser Ile Val Ser Pro Thr Ala Ala Glu Lys Ser Arg Lys Ala
1010 1015 1020
Gln Ile Phe His Val Leu Lys His Ile Lys Asn Ser Arg Ile Lys
1025 1030 1035
Met Gly Leu Val Lys Tyr Asp Asn Ser Asp Asn Ile Gly Gly Asp
1040 1045 1050
His Val Cys Ser Arg Thr Tyr Ala Val Asn Pro Glu Lys Gln Glu
1055 1060 1065
Glu Cys Val Lys Phe Cys Glu Glu Asn Trp Glu Asn Cys Lys Asn
1070 1075 1080
Lys Pro Ser Pro Gly Tyr Cys Leu Ala Lys Leu Lys Asn Thr Asn
1085 1090 1095
Glu Cys Phe Phe Cys Tyr Val
1100 1105
<210> 61
<211> 930
<212> PRT
<213> 恶性疟原虫
<400> 61
Met Lys Phe Ser Ile Ser Leu Phe Leu Ile Leu Cys Val Leu Phe Cys
1 5 10 15
Lys Asn Asp Ile Lys Cys Thr Thr Val Asp Glu Ser Thr Lys Glu Gly
20 25 30
Ser Gln Asn Pro Lys Asn Ser Ser Ser Thr Thr Pro Ala Ser Gly Ser
35 40 45
Gln Lys Gly Ser Ser Ser Glu Ser Pro Gly Ser Ser Val Glu Lys Gln
50 55 60
Ser Gln Glu Ser Asn Lys Glu Ser Thr Asn Gly Gly Asn Val Val Ser
65 70 75 80
Gln Gly Thr Pro Ala Asn Thr Phe Gly Gln Asn Ser Asn Asn Pro Ser
85 90 95
Asp Ser Pro Gln Gly Thr Ser Thr Leu Pro Ser Pro Pro Lys Ser Ile
100 105 110
Asp Val Lys Ser Ala Phe Leu Lys His Tyr Lys Gly Val Lys Val Thr
115 120 125
Gly Ser Cys Asn Ala Asn Phe Gln Leu Phe Leu Val Pro His Ile Phe
130 135 140
Ile Asn Val Glu Thr Lys Glu Asn Asn Ile Gln Leu Asp Val Lys Phe
145 150 155 160
Leu Lys Leu Thr Lys Arg Ile Asp Phe Ala Lys Asp Lys Ser Met Leu
165 170 175
Lys Asn Lys Cys Glu Ser Gly Lys Asn Gln Thr Phe Lys Phe Val Leu
180 185 190
Tyr Phe Lys Asp Asp Ile Leu Thr Ile Lys Trp Lys Val Tyr Glu Glu
195 200 205
Lys Ser Ala Thr Pro Gln Lys Ser Glu Glu Asn Thr Val Asp Ile Lys
210 215 220
Leu Tyr Lys Leu Pro Lys Leu Asp Gln Thr Ile Thr Ser Ile Gln Val
225 230 235 240
His Thr Leu Ser Ile Glu Gly Thr Ser Tyr Leu Met Glu Ser Lys Asp
245 250 255
Tyr Ser Leu Gly Asn Asn Leu Pro Glu Lys Cys Asp Ala Ile Ala Ser
260 265 270
Asp Cys Phe Leu Ser Gly Asn Ile Asn Val Glu Lys Cys Leu Lys Cys
275 280 285
Thr Leu Lys Val Lys Lys Val Glu Ala Ser Asp Glu Cys Tyr Lys Tyr
290 295 300
Val Ser Lys Asp Lys Pro Lys Glu Thr Lys Leu Ala Val Ser Gly Ser
305 310 315 320
Glu Val Lys Glu Val Lys Ala Ala Ser Val Asp His Ser Asn Asp Lys
325 330 335
Glu Tyr Glu Leu Ser Gln Ser Ile Asn Asn Ile Leu Asn Lys Met Tyr
340 345 350
Lys Lys Glu Ser Asn Asp Glu Lys Asn Asn Lys Lys Glu Leu Ile Lys
355 360 365
Leu Glu Asp Ala Asp Asp Ser Leu Gln Lys Glu Leu Asn Lys Tyr Cys
370 375 380
Asn Ser Leu Lys Glu Val Asp Leu Asn Gly Val Leu Ser Lys Asn Glu
385 390 395 400
Val Gly Asn Glu Lys Asp Val Phe Asn Asn Leu Thr Thr Leu Leu Lys
405 410 415
Glu His Met Leu Glu Ser His His Val Val Phe Glu Lys Leu Lys Asn
420 425 430
Ser Ala Leu Cys Leu Lys Asn Ile Asp Asp Trp Leu Lys Asn Lys Asn
435 440 445
Gly Leu Ile Val Pro Pro Ser Lys Tyr Lys Leu Lys Asp Thr Asn Glu
450 455 460
Lys Lys Glu Leu Asn Asn Asn Val Glu Val Ile Glu Asp Met Phe Lys
465 470 475 480
Ala Asn Glu His Gly Ile Val Asp Leu Thr Lys Phe Pro Ile Asp Thr
485 490 495
Asn Tyr Ser Ser Tyr Lys His Ile Asp His Thr Tyr Cys Asn Asn Asp
500 505 510
Tyr Cys Asn Trp Ser Lys Asp Lys Asn Ser Cys Ile Ser Lys Ile Asn
515 520 525
Val Glu Asp Gln Lys Asn Cys Ala Leu Ser Trp Ala Phe Ala Ser Lys
530 535 540
Tyr His Leu Glu Thr Ile Lys Cys Met Lys Gly Tyr Glu His Ile Pro
545 550 555 560
Ile Ser Ser Leu Tyr Ile Ala Asn Cys Ser Lys Asn Glu Lys Lys Asp
565 570 575
Val Cys Thr Glu Gly Ser Asn Pro Leu Lys Val Leu Gln Met Ile Val
580 585 590
Glu Lys Gly Phe Leu Pro Thr Glu Gly Asp Tyr Ser Tyr Glu Gln Ser
595 600 605
Lys Val Gly Glu Thr Cys Pro Glu Val Gln Asn Gly Trp Val Asn Leu
610 615 620
Trp Ala Asn Ala Lys Leu Leu Glu Gln Asn Asn Asp Glu His Asn Ser
625 630 635 640
Leu Ser Thr Lys Gly Tyr Thr Ala Tyr Glu Ser Glu Ala Phe Gln Lys
645 650 655
Asp Met His Ser Phe Val Lys Leu Ile Lys Asp Glu Ile Met Asn Lys
660 665 670
Gly Ser Val Ile Ala Tyr Val Lys Ala Asp Lys Ile Met Ala Tyr Glu
675 680 685
Phe Asn Gly Lys Lys Val Gln Asn Leu Cys Gly Asp Lys Thr Pro Asp
690 695 700
His Ala Val Asn Ile Ile Gly Tyr Gly Asn Tyr Ile Asn Asp Glu His
705 710 715 720
Gln Lys Lys Ser Tyr Trp Ile Val Arg Asn Ser Trp Gly Lys His Trp
725 730 735
Gly Asp Lys Gly His Phe Lys Val Asp Met Tyr Gly Pro Ser Asp Cys
740 745 750
Glu Asp Asn Phe Ile His Ser Val Val Ile Phe Asn Val Asp Leu Pro
755 760 765
Ile Asn Gln Glu Ser Val Lys Lys Glu Pro Lys Ile Tyr Asn Tyr Tyr
770 775 780
Leu Lys Ala Ser Pro Asp Phe Tyr His Asn Leu Tyr Tyr Lys Asn Phe
785 790 795 800
Asp Ser Gln Lys Gly Lys Ala Asp Gln Ala Glu Asn Lys Lys Ser Tyr
805 810 815
Leu Tyr Gly Gln Glu Glu Ser Thr Ser Glu Gln Leu Pro Ser Ser Leu
820 825 830
Ser Ser Pro Gln Asn Asn Lys Gln Ser Glu Arg Ser Lys Glu Lys Val
835 840 845
Asp Ile Phe His Val Leu Lys His Ile Lys Asp Ser Lys Ile Lys Met
850 855 860
Gly Ile Val Lys Tyr Asp His Ser Asp Ala Leu Gly Glu Asp Asn Val
865 870 875 880
Cys Ser Arg Ser Tyr Ser Ser Asn Pro Glu Lys Gln Glu Gly Cys Val
885 890 895
Lys Phe Cys Asn Glu Asn Trp Gly Lys Cys Lys Asp Ala Ala Ser Pro
900 905 910
Gly Phe Cys Leu Ser Glu Leu Glu Lys Thr Asn Asp Cys Phe Phe Cys
915 920 925
Tyr Ile
930
<210> 62
<211> 962
<212> PRT
<213> 恶性疟原虫
<400> 62
Met Lys Ile His Ile Phe Leu Ile Ala Thr Ile Tyr Val Leu Phe Ser
1 5 10 15
Glu Lys Leu Ile Lys Trp Thr Thr Ala Ser Thr Thr Gln Gly Gly Asp
20 25 30
Thr Asp Thr His Pro Gly Thr Pro Pro Gly Glu Gly Ser Asp Val Ser
35 40 45
Gln Gly Ala Gly Gln Asp Ala Ser Gln Gly Ala Gly Gln Asp Ala Asn
50 55 60
Pro Asp Pro Thr Leu Pro Lys Pro Pro Ser Pro Pro Ala Asp Asp Thr
65 70 75 80
Lys Asp Thr Gly Ser Gln Gly Asp Ala Asp Ser Ser Ser Ser Lys Ile
85 90 95
Glu Ile Pro Pro Leu Val Lys Pro Glu Asn His Lys Thr Ile Val Ser
100 105 110
Ala Met Leu Lys Asn Tyr Lys Gly Val Lys Val Thr Gly Thr Cys Gly
115 120 125
Ala Asp Phe Gly Leu Phe Leu Val Pro His Ile Tyr Val His Val Lys
130 135 140
Ser Glu Asp Thr Glu Ile Glu Leu Ser Ser Glu Leu Ala Pro Pro Glu
145 150 155 160
Met Gln Thr Lys Phe Asp Lys Thr Gln Leu Lys Lys Phe Cys Val Lys
165 170 175
Asp Asp Thr Lys Lys Phe Asp Phe Ile Ala Tyr Ile Tyr Lys Asp Ile
180 185 190
Leu Val Phe Lys Trp Lys Val Tyr Glu Glu Gly Leu Ser Lys Glu Gln
195 200 205
Asp Val Asp Glu Met Lys Tyr Leu Leu Pro Asn Leu Lys Gln Pro Ile
210 215 220
Thr Ser Ile Gln Val His Ser Trp Thr Gly Thr Lys Glu Ser Tyr Ile
225 230 235 240
Leu Glu Ser Lys Asp Tyr Val Leu Gly Glu Gly Met Pro Glu Lys Cys
245 250 255
Asp Ala Ile Ala Thr Asp Cys Phe Leu Ser Gly Phe Thr Asp Ile Gly
260 265 270
Lys Cys Phe Gln Cys Lys Leu Leu Met Gln Glu Lys Asn Ile Asn Asp
275 280 285
Ser Cys Phe Lys Tyr Val Ser Ser Asn Gln Lys Glu Leu Ile Lys Lys
290 295 300
Gln Leu Lys Ile Thr Ala Gln Asp Asp Glu Glu Ser Ser Glu Tyr His
305 310 315 320
Leu Ser Glu Ser Ile Lys Asn Leu Leu Lys Asn Ile Tyr Lys Lys Asn
325 330 335
Asn Asp Asp Asn Lys Lys Lys Glu Leu Leu His Phe Glu Asn Val Asn
340 345 350
Ser Ala Leu Lys Ser Glu Leu Leu Asn Tyr Cys Asn Leu Leu Lys Glu
355 360 365
Val Asn Met Asn Gly Val Leu Lys Asp His Gln Leu Gly Asn Val Gln
370 375 380
Asp Val Phe Asn Asn Leu Thr Lys Leu Leu Glu Glu His Lys Glu Glu
385 390 395 400
Asn Asp Asn Val Leu Tyr His Lys Met Lys Asn Glu Ala Leu Cys Leu
405 410 415
Lys Asn Val Asn Asp Trp Met Lys Asn Lys Thr Gly Leu Leu Leu Pro
420 425 430
Gln Leu Ser Tyr Asp Leu Thr Tyr Lys Asn Asn Asn Phe Thr Glu Phe
435 440 445
Thr Gln Asn Lys Ser Tyr Thr Ser Gln Asn Ile Val Asp Lys Leu Tyr
450 455 460
Cys Asn His Glu Tyr Cys Asn Arg Leu Lys Asp His Asn Asn Cys Ile
465 470 475 480
Ser Lys Ile Asn Val Glu Asp Gln Lys Asn Cys Ala Leu Ser Trp Ala
485 490 495
Phe Ala Ser Lys Tyr His Leu Glu Thr Ile Lys Cys Met Lys Gly Tyr
500 505 510
Glu Pro Leu Asn Ala Ser Val Leu Tyr Val Thr Asn Cys Leu Lys Asn
515 520 525
Lys Asn Lys Asp Val Cys Thr Glu Gly Ser Asn Pro Leu Val Phe Leu
530 535 540
Glu Thr Ile Glu Glu Lys Gly Phe Leu Pro Thr Glu Ser Asn Tyr Pro
545 550 555 560
Tyr Asp Gln Ser Lys Val Gly Asp Ile Cys Pro Gln Leu Gln Asn Asp
565 570 575
Trp Asp Asn Val Phe Glu Asn Thr Lys Val Leu Asp Tyr Asn Asn Gly
580 585 590
Pro Phe Ser Val Gly Thr Lys Gly Tyr Ile Ala Tyr Glu Ser Glu Ala
595 600 605
Phe Gln Lys Asp Met His Ser Phe Val Lys Leu Val Lys Asp Glu Ile
610 615 620
Met Asn Lys Gly Ser Val Ile Ala Tyr Val Lys Ala Glu Asn Val Leu
625 630 635 640
Gly Tyr Glu Leu Asn Gly Lys Lys Val Gln Asn Leu Cys Gly Asp Lys
645 650 655
Thr Pro Asp His Val Val Asn Ile Val Gly Tyr Gly Asn Tyr Ile Asn
660 665 670
Asn Lys Gly Glu Lys Lys Ser Tyr Trp Ile Val Arg Asn Ser Trp Gly
675 680 685
Lys Tyr Trp Gly Asp Asp Gly Tyr Phe Lys Val Asp Met Tyr Gly Pro
690 695 700
Ser Thr Cys Glu Asp Asn Phe Ile His Thr Val Val Val Phe Asn Val
705 710 715 720
Gln Val Pro Ile Asn Glu Lys Phe Asp Lys Lys Glu His Asp Ile Tyr
725 730 735
Asn Tyr Tyr Leu Lys Thr Ser Pro Glu Phe Tyr His Asn Leu Tyr Tyr
740 745 750
Lys Thr Phe Asn Ser Asn Lys Glu Glu Lys Ser Met Asn Lys Asn Ser
755 760 765
Tyr Val Tyr Gly Gln Asp Thr Thr Pro Val Glu Asn Glu Ala Pro Arg
770 775 780
Ser Gly Val Gln Lys Pro Thr Glu Leu Ser Ser Thr Glu Ser Gln Thr
785 790 795 800
Val Ser Pro Pro Asn Glu Ser Gln Thr Glu Ser Leu Leu Ser Gly Gly
805 810 815
Ser Gln Val Thr Asn Pro Thr Leu Thr Gln Ser Thr Ser Ser Ser Ser
820 825 830
Gly Gln Gln Glu Thr Gly Pro Leu Ser Thr Gln Gly Leu Ser Pro Ala
835 840 845
Thr Gly Asp Pro Lys Gly Lys Glu Gln Glu Ala Ser Pro Ala Glu Gly
850 855 860
Leu Ser Gly Val Leu Asn Pro Thr Lys Glu Val Thr Ser Glu Glu Lys
865 870 875 880
Ile Gln Ile Ile His Leu Leu Lys His Ile Lys Asn Ser Lys Ile Arg
885 890 895
Arg Gly Leu Val Lys Tyr Asn His Glu Phe Glu Val Gly Asp Asn Ser
900 905 910
Cys Ser Arg Ser Thr Ser Lys Asn Ala Glu Met His Asp Glu Cys Val
915 920 925
Asn Ile Cys Glu Lys Tyr Trp Pro Glu Cys Arg Gly Thr Ala Val Pro
930 935 940
Gly Tyr Cys Leu Ser Thr His Asp Asp Lys Asn Glu Cys Asp Phe Cys
945 950 955 960
Tyr Val
<210> 63
<211> 997
<212> PRT
<213> 恶性疟原虫
<400> 63
Met Lys Ser Tyr Ile Ser Leu Phe Phe Ile Leu Cys Val Ile Phe Asn
1 5 10 15
Lys Asn Val Ile Lys Cys Thr Gly Glu Ser Gln Thr Gly Asn Thr Gly
20 25 30
Gly Gly Gln Ala Gly Asn Thr Gly Gly Asp Gln Ala Gly Ser Thr Gly
35 40 45
Gly Ser Pro Gln Gly Ser Thr Gly Ala Ser Pro Gln Gly Ser Thr Gly
50 55 60
Ala Ser Pro Gln Gly Ser Thr Gly Ala Ser Gln Pro Gly Ser Ser Glu
65 70 75 80
Pro Ser Asn Pro Val Ser Ser Gly His Ser Val Ser Thr Val Ser Val
85 90 95
Ser Gln Thr Ser Thr Ser Ser Glu Lys Gln Asp Thr Ile Gln Val Lys
100 105 110
Ser Ala Leu Leu Lys Asp Tyr Met Gly Leu Lys Val Thr Gly Pro Cys
115 120 125
Asn Glu Asn Phe Ile Met Phe Leu Val Pro His Ile Tyr Ile Asp Val
130 135 140
Asp Thr Glu Asp Thr Asn Ile Glu Leu Arg Thr Thr Leu Lys Lys Thr
145 150 155 160
Asn Asn Ala Ile Ser Phe Glu Ser Asn Ser Gly Ser Leu Glu Lys Lys
165 170 175
Lys Tyr Val Lys Leu Pro Ser Asn Gly Thr Thr Gly Glu Gln Gly Ser
180 185 190
Ser Thr Gly Thr Val Arg Gly Asp Thr Glu Pro Ile Ser Asp Ser Ser
195 200 205
Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser Ser
210 215 220
Ser Ser Ser Ser Ser Ser Ser Ser Ser Glu Ser Leu Pro Ala Asn Gly
225 230 235 240
Pro Asp Ser Pro Thr Val Lys Pro Pro Arg Asn Leu Gln Asn Ile Cys
245 250 255
Glu Thr Gly Lys Asn Phe Lys Leu Val Val Tyr Ile Lys Glu Asn Thr
260 265 270
Leu Ile Leu Lys Trp Lys Val Tyr Gly Glu Thr Lys Asp Thr Thr Glu
275 280 285
Asn Asn Lys Val Asp Val Arg Lys Tyr Leu Ile Asn Glu Lys Glu Thr
290 295 300
Pro Phe Thr Asn Ile Leu Ile His Ala Tyr Lys Glu His Asn Gly Thr
305 310 315 320
Asn Leu Ile Glu Ser Lys Asn Tyr Ala Ile Gly Ser Asp Ile Pro Glu
325 330 335
Lys Cys Asp Thr Leu Ala Ser Asn Cys Phe Leu Ser Gly Asn Phe Asn
340 345 350
Ile Glu Lys Cys Phe Gln Cys Ala Leu Leu Val Glu Lys Glu Asn Lys
355 360 365
Asn Asp Val Cys Tyr Lys Tyr Leu Ser Glu Asp Ile Val Ser Lys Phe
370 375 380
Lys Glu Ile Lys Ala Glu Thr Glu Asp Asp Asp Glu Asp Asp Tyr Thr
385 390 395 400
Glu Tyr Lys Leu Thr Glu Ser Ile Asp Asn Ile Leu Val Lys Met Phe
405 410 415
Lys Thr Asn Glu Asn Asn Asp Lys Ser Glu Leu Ile Lys Leu Glu Glu
420 425 430
Val Asp Asp Ser Leu Lys Leu Glu Leu Met Asn Tyr Cys Ser Leu Leu
435 440 445
Lys Asp Val Asp Thr Thr Gly Thr Leu Asp Asn Tyr Gly Met Gly Asn
450 455 460
Glu Met Asp Ile Phe Asn Asn Leu Lys Arg Leu Leu Ile Tyr His Ser
465 470 475 480
Glu Glu Asn Ile Asn Thr Leu Lys Asn Lys Phe Arg Asn Ala Ala Val
485 490 495
Cys Leu Lys Asn Val Asp Asp Trp Ile Val Asn Lys Arg Gly Leu Val
500 505 510
Leu Pro Glu Leu Asn Tyr Asp Leu Glu Tyr Phe Asn Glu His Leu Tyr
515 520 525
Asn Asp Lys Asn Ser Pro Glu Asp Lys Asp Asn Lys Gly Lys Gly Val
530 535 540
Val His Val Asp Thr Thr Leu Glu Lys Glu Asp Thr Leu Ser Tyr Asp
545 550 555 560
Asn Ser Asp Asn Met Phe Cys Asn Lys Glu Tyr Cys Asn Arg Leu Lys
565 570 575
Asp Glu Asn Asn Cys Ile Ser Asn Leu Gln Val Glu Asp Gln Gly Asn
580 585 590
Cys Asp Thr Ser Trp Ile Phe Ala Ser Lys Tyr His Leu Glu Thr Ile
595 600 605
Arg Cys Met Lys Gly Tyr Glu Pro Thr Lys Ile Ser Ala Leu Tyr Val
610 615 620
Ala Asn Cys Tyr Lys Gly Glu His Lys Asp Arg Cys Asp Glu Gly Ser
625 630 635 640
Ser Pro Met Glu Phe Leu Gln Ile Ile Glu Asp Tyr Gly Phe Leu Pro
645 650 655
Ala Glu Ser Asn Tyr Pro Tyr Asn Tyr Val Lys Val Gly Glu Gln Cys
660 665 670
Pro Lys Val Glu Asp His Trp Met Asn Leu Trp Asp Asn Gly Lys Ile
675 680 685
Leu His Asn Lys Asn Glu Pro Asn Ser Leu Asp Gly Lys Gly Tyr Thr
690 695 700
Ala Tyr Glu Ser Glu Arg Phe His Asp Asn Met Asp Ala Phe Val Lys
705 710 715 720
Ile Ile Lys Thr Glu Val Met Asn Lys Gly Ser Val Ile Ala Tyr Ile
725 730 735
Lys Ala Glu Asn Val Met Gly Tyr Glu Phe Ser Gly Lys Lys Val Gln
740 745 750
Asn Leu Cys Gly Asp Asp Thr Ala Asp His Ala Val Asn Ile Val Gly
755 760 765
Tyr Gly Asn Tyr Val Asn Ser Glu Gly Glu Lys Lys Ser Tyr Trp Ile
770 775 780
Val Arg Asn Ser Trp Gly Pro Tyr Trp Gly Asp Glu Gly Tyr Phe Lys
785 790 795 800
Val Asp Met Tyr Gly Pro Thr His Cys His Phe Asn Phe Ile His Ser
805 810 815
Val Val Ile Phe Asn Val Asp Leu Pro Met Asn Asn Lys Thr Thr Lys
820 825 830
Lys Glu Ser Lys Ile Tyr Asp Tyr Tyr Leu Lys Ala Ser Pro Glu Phe
835 840 845
Tyr His Asn Leu Tyr Phe Lys Asn Phe Asn Val Gly Lys Lys Asn Leu
850 855 860
Phe Ser Glu Lys Glu Asp Asn Glu Asn Asn Lys Lys Leu Gly Asn Asn
865 870 875 880
Tyr Ile Ile Phe Gly Gln Asp Thr Ala Gly Ser Gly Gln Ser Gly Lys
885 890 895
Glu Ser Asn Thr Ala Leu Glu Ser Ala Gly Thr Ser Asn Glu Val Ser
900 905 910
Glu Arg Val His Val Tyr His Ile Leu Lys His Ile Lys Asp Gly Lys
915 920 925
Ile Arg Met Gly Met Arg Lys Tyr Ile Asp Thr Gln Asp Val Asn Lys
930 935 940
Lys His Ser Cys Thr Arg Ser Tyr Ala Phe Asn Pro Glu Asn Tyr Glu
945 950 955 960
Lys Cys Val Asn Leu Cys Asn Val Asn Trp Lys Thr Cys Glu Glu Lys
965 970 975
Thr Ser Pro Gly Leu Cys Leu Ser Lys Leu Asp Thr Asn Asn Glu Cys
980 985 990
Tyr Phe Cys Tyr Val
995
<210> 64
<211> 1233
<212> PRT
<213> 恶性疟原虫
<400> 64
Met Arg Asn Leu Phe His Ile Thr Ile Cys Leu Val Thr Leu Asn Leu
1 5 10 15
Phe Ile Leu Glu Ile Asn Ala Lys Thr Asn Thr Ser Glu Asn Arg Asn
20 25 30
Lys Arg Ile Gly Gly Pro Lys Leu Arg Gly Asn Val Thr Ser Asn Ile
35 40 45
Lys Phe Pro Ser Asp Asn Lys Gly Lys Ile Ile Arg Gly Ser Asn Asp
50 55 60
Lys Leu Asn Lys Asn Ser Glu Asp Val Leu Glu Gln Ser Glu Lys Ser
65 70 75 80
Leu Val Ser Glu Asn Val Pro Ser Gly Leu Asp Ile Asp Asp Ile Pro
85 90 95
Lys Glu Ser Ile Phe Ile Gln Glu Asp Gln Glu Gly Gln Thr His Ser
100 105 110
Glu Leu Asn Pro Glu Thr Ser Glu His Ser Lys Asp Leu Asn Asn Asn
115 120 125
Asp Ser Lys Asn Glu Ser Ser Asp Ile Ile Ser Val Asn Asn Lys Ser
130 135 140
Asn Lys Val Gln Asn His Phe Glu Ser Leu Ser Asp Leu Glu Leu Leu
145 150 155 160
Glu Asn Ser Ser Gln Asp Asn Leu Asp Lys Asp Thr Ile Ser Thr Glu
165 170 175
Pro Phe Pro Asn Gln Lys His Lys Asp Leu Gln Gln Asp Leu Asn Asp
180 185 190
Glu Pro Leu Glu Pro Phe Pro Thr Gln Ile His Lys Asp Tyr Lys Glu
195 200 205
Lys Asn Leu Ile Asn Glu Glu Asp Ser Glu Pro Phe Pro Arg Gln Lys
210 215 220
His Lys Lys Val Asp Asn His Asn Glu Glu Lys Asn Val Phe His Glu
225 230 235 240
Asn Gly Ser Ala Asn Gly Asn Gln Gly Ser Leu Lys Leu Lys Ser Phe
245 250 255
Asp Glu His Leu Lys Asp Glu Lys Ile Glu Asn Glu Pro Leu Val His
260 265 270
Glu Asn Leu Ser Ile Pro Asn Asp Pro Ile Glu Gln Ile Leu Asn Gln
275 280 285
Pro Glu Gln Glu Thr Asn Ile Gln Glu Gln Leu Tyr Asn Glu Lys Gln
290 295 300
Asn Val Glu Glu Lys Gln Asn Ser Gln Ile Pro Ser Leu Asp Leu Lys
305 310 315 320
Glu Pro Thr Asn Glu Asp Ile Leu Pro Asn His Asn Pro Leu Glu Asn
325 330 335
Ile Lys Gln Ser Glu Ser Glu Ile Asn His Val Gln Asp His Ala Leu
340 345 350
Pro Lys Glu Asn Ile Ile Asp Lys Leu Asp Asn Gln Lys Glu His Ile
355 360 365
Asp Gln Ser Gln His Asn Ile Asn Val Leu Gln Glu Asn Asn Ile Asn
370 375 380
Asn His Gln Leu Glu Pro Gln Glu Lys Pro Asn Ile Glu Ser Phe Glu
385 390 395 400
Pro Lys Asn Ile Asp Ser Glu Ile Ile Leu Pro Glu Asn Val Glu Thr
405 410 415
Glu Glu Ile Ile Asp Asp Val Pro Ser Pro Lys His Ser Asn His Glu
420 425 430
Thr Phe Glu Glu Glu Thr Ser Glu Ser Glu His Glu Glu Ala Val Ser
435 440 445
Glu Lys Asn Ala His Glu Thr Val Glu His Glu Glu Thr Val Ser Gln
450 455 460
Glu Ser Asn Pro Glu Lys Ala Asp Asn Asp Gly Asn Val Ser Gln Asn
465 470 475 480
Ser Asn Asn Glu Leu Asn Glu Asn Glu Phe Val Glu Ser Glu Lys Ser
485 490 495
Glu His Glu Pro Ala Glu Asn Glu Glu Ser Ser Leu Glu Glu Gly His
500 505 510
His Glu Glu Ile Val Pro Glu Gln Asn Asn Glu Glu Ser Gly Glu Ser
515 520 525
Lys Leu Val Asp Asn Asp Glu Gly Gly Phe Glu Glu Ala His His Glu
530 535 540
Asn Phe Ser Ser Glu Val Ser Asn Ser Glu Leu Asn Glu Asn Glu Phe
545 550 555 560
Val Glu Ser Asp Lys Ser Val Thr Glu Pro Ala Glu His Glu Glu Val
565 570 575
Val Ser Glu Glu Ser Asn Pro Glu Pro Ala Glu Asn Glu Glu Ser Ser
580 585 590
Ile Glu Glu Ala His Gln Glu Glu Ile Val Pro Glu Gln Asn Asp Glu
595 600 605
Glu Ser Gly Glu Ser Gly Leu Val Asp Asn Glu Glu Gly Asp Phe Glu
610 615 620
Glu Pro Asn His Glu Glu Phe Glu Pro Asp Gln Asn Asp Ser Glu Leu
625 630 635 640
Ser Glu Asn Glu Leu Val Glu Ser Glu Lys Ser Val Ser Glu Pro Ala
645 650 655
Glu His Val Glu Ile Val Ser Glu Lys Ser Val Ser Glu Pro Ala Glu
660 665 670
His Val Glu Ile Val Ser Glu Lys Ser Thr Ser Glu Pro Ala Glu His
675 680 685
Val Glu Ser Val Ser Glu Gln Ser Asn Asn Glu Pro Ser Glu Lys Lys
690 695 700
Asp Gly Pro Val Pro Ser Lys Pro Phe Glu Glu Ile Glu Lys Val Asp
705 710 715 720
Val Gln Pro Lys Ile Val Asp Leu Gln Ile Ile Glu Pro Asn Phe Val
725 730 735
Asp Ser Gln Pro Asn Pro Gln Glu Pro Val Glu Pro Ser Phe Val Lys
740 745 750
Ile Glu Lys Val Pro Ser Glu Glu Asn Lys His Ala Ser Val Asp Pro
755 760 765
Glu Val Lys Glu Lys Glu Asn Val Ser Glu Val Val Glu Glu Lys Gln
770 775 780
Asn Ser Gln Glu Ser Val Glu Glu Ile Pro Val Asn Glu Asp Glu Phe
785 790 795 800
Glu Asp Val His Thr Glu Gln Leu Asp Leu Asp His Lys Thr Val Asp
805 810 815
Pro Glu Ile Val Glu Val Glu Glu Ile Pro Ser Glu Leu His Glu Asn
820 825 830
Glu Val Ala His Pro Glu Ile Val Glu Ile Glu Glu Val Phe Pro Glu
835 840 845
Pro Asn Gln Asn Asn Glu Phe Gln Glu Ile Asn Glu Asp Asp Lys Ser
850 855 860
Ala His Ile Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu
865 870 875 880
Asp Asp Lys Asn Glu Lys Val Glu His Glu Ile Val Glu Val Glu Glu
885 890 895
Ile Leu Pro Glu Asp Lys Asn Glu Lys Val Gln His Glu Ile Val Glu
900 905 910
Val Glu Glu Ile Leu Pro Glu Asp Lys Asn Glu Lys Val Glu His Glu
915 920 925
Ile Val Glu Val Glu Glu Ile Leu Pro Glu Asp Lys Asn Glu Lys Gly
930 935 940
Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu Asp Lys Asn
945 950 955 960
Glu Lys Val Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu
965 970 975
Asp Lys Asn Glu Lys Gly Gln His Glu Ile Val Glu Val Glu Glu Ile
980 985 990
Leu Pro Glu Asp Lys Asn Glu Lys Val Glu His Glu Ile Val Glu Val
995 1000 1005
Glu Glu Ile Leu Pro Glu Asp Lys Asn Glu Lys Gly Gln His Glu
1010 1015 1020
Ile Val Glu Val Glu Glu Ile Leu Pro Glu Asp Asp Lys Asn Glu
1025 1030 1035
Lys Gly Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu
1040 1045 1050
Ile Val Glu Ile Glu Glu Val Pro Ser Gln Thr Asn Asn Asn Glu
1055 1060 1065
Asn Ile Glu Thr Ile Lys Pro Glu Glu Lys Lys Asn Glu Phe Ser
1070 1075 1080
Val Val Glu Glu Lys Ala Ile Pro Gln Glu Pro Val Val Pro Thr
1085 1090 1095
Leu Asn Glu Asn Glu Asn Val Thr Pro Lys Pro Ser Glu Gly Glu
1100 1105 1110
Ser Thr Lys Pro Asp Ile Val Gln Ile Lys Ile Val Gln Glu Asn
1115 1120 1125
Lys Pro Asn Lys Lys Glu Thr Pro Val Val Asp Gly Pro Lys His
1130 1135 1140
Val Glu Gln Asn Ile Gln Glu Asp Asp Asn Asp Glu Glu Asp Asp
1145 1150 1155
Asp Asp Ile Asp Phe Glu Gly Leu Ser Arg Lys Asp Asp Glu Lys
1160 1165 1170
Asp Ser Ser Asn Lys Asn Lys Lys Lys Ser Ser Phe Ile Thr Tyr
1175 1180 1185
Ile Ser Thr Lys Lys Phe Lys Lys Val Ser Gln Thr Ile Val Ser
1190 1195 1200
Val Met Ile Asn Ala Tyr Asp Gly Val Ile Gln Val Val Ser Thr
1205 1210 1215
Ile Lys Gly Ile Ala Lys Asp Ile Val Ile Phe Phe Gln Asn Ile
1220 1225 1230
<210> 65
<211> 396
<212> PRT
<213> 恶性疟原虫
<400> 65
Asp Ile Pro Lys Glu Ser Ile Phe Ile Gln Glu Asp Gln Glu Gly Gln
1 5 10 15
Thr His Ser Glu Leu Asn Pro Glu Thr Ser Glu His Ser Lys Asp Leu
20 25 30
Asn Asn Asn Asp Ser Lys Asn Glu Ser Ser Asp Ile Ile Ser Val Asn
35 40 45
Asn Lys Ser Asn Lys Val Gln Asn His Phe Glu Ser Leu Ser Asp Leu
50 55 60
Glu Leu Leu Glu Asn Ser Ser Gln Asp Asn Leu Asp Lys Asp Thr Ile
65 70 75 80
Ser Thr Glu Pro Phe Pro Asn Gln Lys His Lys Asp Leu Gln Gln Asp
85 90 95
Leu Asn Asp Glu Pro Leu Glu Pro Phe Pro Thr Gln Ile His Lys Asp
100 105 110
Tyr Lys Glu Lys Asn Leu Ile Asn Glu Glu Asp Ser Glu Pro Phe Pro
115 120 125
Arg Gln Lys His Lys Lys Val Asp Asn His Asn Glu Glu Lys Asn Val
130 135 140
Phe His Glu Asn Gly Ser Ala Asn Gly Asn Gln Gly Ser Leu Lys Leu
145 150 155 160
Lys Ser Phe Asp Glu His Leu Lys Asp Glu Lys Ile Glu Asn Glu Pro
165 170 175
Leu Val His Glu Asn Leu Ser Ile Pro Asn Asp Pro Ile Glu Gln Ile
180 185 190
Leu Asn Gln Pro Glu Gln Glu Thr Asn Ile Gln Glu Gln Leu Tyr Asn
195 200 205
Glu Lys Gln Asn Val Glu Glu Lys Gln Asn Ser Gln Ile Pro Ser Leu
210 215 220
Asp Leu Lys Glu Pro Thr Asn Glu Asp Ile Leu Pro Asn His Asn Pro
225 230 235 240
Leu Glu Asn Ile Lys Gln Ser Glu Ser Glu Ile Asn His Val Gln Asp
245 250 255
His Ala Leu Pro Lys Glu Asn Ile Ile Asp Lys Leu Asp Asn Gln Lys
260 265 270
Glu His Ile Asp Gln Ser Gln His Asn Ile Asn Val Leu Gln Glu Asn
275 280 285
Asn Ile Asn Asn His Gln Leu Glu Pro Gln Glu Lys Pro Asn Ile Glu
290 295 300
Ser Phe Glu Pro Lys Asn Ile Asp Ser Glu Ile Ile Leu Pro Glu Asn
305 310 315 320
Val Glu Thr Glu Glu Ile Ile Asp Asp Val Pro Ser Pro Lys His Ser
325 330 335
Asn His Glu Thr Phe Glu Glu Glu Thr Ser Glu Ser Glu His Glu Glu
340 345 350
Ala Val Ser Glu Lys Asn Ala His Glu Thr Val Glu His Glu Glu Thr
355 360 365
Val Ser Gln Glu Ser Asn Pro Glu Lys Ala Asp Asn Asp Gly Asn Val
370 375 380
Ser Gln Asn Ser Asn Asn Glu Leu Asn Glu Asn Glu
385 390 395
<210> 66
<211> 436
<212> PRT
<213> 恶性疟原虫
<400> 66
Asp Gly Pro Val Pro Ser Lys Pro Phe Glu Glu Ile Glu Lys Val Asp
1 5 10 15
Val Gln Pro Lys Ile Val Asp Leu Gln Ile Ile Glu Pro Asn Phe Val
20 25 30
Asp Ser Gln Pro Asn Pro Gln Glu Pro Val Glu Pro Ser Phe Val Lys
35 40 45
Ile Glu Lys Val Pro Ser Glu Glu Asn Lys His Ala Ser Val Asp Pro
50 55 60
Glu Val Lys Glu Lys Glu Asn Val Ser Glu Val Val Glu Glu Lys Gln
65 70 75 80
Asn Ser Gln Glu Ser Val Glu Glu Ile Pro Val Asn Glu Asp Glu Phe
85 90 95
Glu Asp Val His Thr Glu Gln Leu Asp Leu Asp His Lys Thr Val Asp
100 105 110
Pro Glu Ile Val Glu Val Glu Glu Ile Pro Ser Glu Leu His Glu Asn
115 120 125
Glu Val Ala His Pro Glu Ile Val Glu Ile Glu Glu Val Phe Pro Glu
130 135 140
Pro Asn Gln Asn Asn Glu Phe Gln Glu Ile Asn Glu Asp Asp Lys Ser
145 150 155 160
Ala His Ile Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu
165 170 175
Asp Asp Lys Asn Glu Lys Val Glu His Glu Ile Val Glu Val Glu Glu
180 185 190
Ile Leu Pro Glu Asp Lys Asn Glu Lys Val Gln His Glu Ile Val Glu
195 200 205
Val Glu Glu Ile Leu Pro Glu Asp Lys Asn Glu Lys Val Glu His Glu
210 215 220
Ile Val Glu Val Glu Glu Ile Leu Pro Glu Asp Lys Asn Glu Lys Gly
225 230 235 240
Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu Asp Lys Asn
245 250 255
Glu Lys Val Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu
260 265 270
Asp Lys Asn Glu Lys Gly Gln His Glu Ile Val Glu Val Glu Glu Ile
275 280 285
Leu Pro Glu Asp Lys Asn Glu Lys Val Glu His Glu Ile Val Glu Val
290 295 300
Glu Glu Ile Leu Pro Glu Asp Lys Asn Glu Lys Gly Gln His Glu Ile
305 310 315 320
Val Glu Val Glu Glu Ile Leu Pro Glu Asp Asp Lys Asn Glu Lys Gly
325 330 335
Gln His Glu Ile Val Glu Val Glu Glu Ile Leu Pro Glu Ile Val Glu
340 345 350
Ile Glu Glu Val Pro Ser Gln Thr Asn Asn Asn Glu Asn Ile Glu Thr
355 360 365
Ile Lys Pro Glu Glu Lys Lys Asn Glu Phe Ser Val Val Glu Glu Lys
370 375 380
Ala Ile Pro Gln Glu Pro Val Val Pro Thr Leu Asn Glu Asn Glu Asn
385 390 395 400
Val Thr Pro Lys Pro Ser Glu Gly Glu Ser Thr Lys Pro Asp Ile Val
405 410 415
Gln Ile Lys Ile Val Gln Glu Asn Lys Pro Asn Lys Lys Glu Thr Pro
420 425 430
Val Val Asp Gly
435
<210> 67
<211> 824
<212> PRT
<213> 恶性疟原虫
<400> 67
Met Arg Leu Ser Lys Val Ser Asp Ile Lys Ser Thr Gly Val Ser Asn
1 5 10 15
Tyr Lys Asn Phe Asn Ser Lys Asn Ser Ser Lys Tyr Ser Leu Met Glu
20 25 30
Val Ser Lys Lys Asn Glu Lys Lys Asn Ser Leu Gly Ala Phe His Ser
35 40 45
Lys Lys Ile Leu Leu Ile Phe Gly Ile Ile Tyr Val Val Leu Leu Asn
50 55 60
Ala Tyr Ile Cys Gly Asp Lys Tyr Glu Lys Ala Val Asp Tyr Gly Phe
65 70 75 80
Arg Glu Ser Arg Ile Leu Ala Glu Gly Glu Asp Thr Cys Ala Arg Lys
85 90 95
Glu Lys Thr Thr Leu Arg Lys Ser Lys Gln Lys Thr Ser Thr Arg Thr
100 105 110
Val Ala Thr Gln Thr Lys Lys Asp Glu Glu Asn Lys Ser Val Val Thr
115 120 125
Glu Glu Gln Lys Val Glu Ser Asp Ser Glu Lys Gln Lys Arg Thr Lys
130 135 140
Lys Val Val Lys Lys Gln Ile Asn Ile Gly Asp Thr Glu Asn Gln Lys
145 150 155 160
Glu Gly Lys Asn Val Lys Lys Val Ile Lys Lys Glu Lys Lys Lys Glu
165 170 175
Glu Ser Gly Lys Pro Glu Glu Asn Lys His Ala Asn Glu Ala Ser Lys
180 185 190
Lys Gln Glu Pro Lys Ala Ser Lys Val Ser Gln Lys Pro Ser Thr Ser
195 200 205
Thr Arg Ser Asn Asn Glu Val Lys Ile Arg Ala Ala Ser Asn Gln Glu
210 215 220
Thr Leu Thr Ser Ala Asp Pro Glu Gly Gln Ile Met Arg Glu Tyr Ala
225 230 235 240
Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Ile Phe Tyr Lys Ile Leu
245 250 255
Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn
260 265 270
Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gln Ile Met Arg Glu
275 280 285
Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu Ile Phe Tyr Lys
290 295 300
Ile Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn Ala
305 310 315 320
Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gln Ile Met
325 330 335
Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val Phe
340 345 350
His Lys Ile Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg
355 360 365
Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gln
370 375 380
Ile Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu
385 390 395 400
Val Phe His Lys Ile Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu
405 410 415
Arg Arg Asn Ala Asp Asn Lys Glu Leu Thr Ser Ser Asp Pro Glu Gly
420 425 430
Gln Ile Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu
435 440 445
Glu Val Phe His Lys Ile Leu Thr Asn Thr Asp Pro Asn Asp Glu Val
450 455 460
Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro
465 470 475 480
Glu Gly Gln Ile Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys
485 490 495
His Leu Glu Val Phe His Lys Ile Leu Thr Asn Thr Asp Pro Asn Asp
500 505 510
Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala
515 520 525
Asp Pro Glu Gly Gln Ile Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr
530 535 540
Arg Lys His Leu Glu Ile Phe His Lys Ile Leu Thr Asn Thr Asp Pro
545 550 555 560
Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Asp Leu Thr
565 570 575
Ser Ala Asp Pro Glu Gly Gln Ile Met Arg Glu Tyr Ala Ala Asp Pro
580 585 590
Glu Tyr Arg Lys His Leu Glu Ile Phe Tyr Lys Ile Leu Thr Asn Thr
595 600 605
Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys Glu Glu
610 615 620
Leu Thr Ser Ser Asp Pro Glu Gly Gln Ile Met Arg Glu Tyr Ala Ala
625 630 635 640
Asp Pro Glu Tyr Arg Lys His Leu Glu Ile Phe His Lys Ile Leu Thr
645 650 655
Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp Asn Lys
660 665 670
Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gln Ile Met Arg Glu Tyr
675 680 685
Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Ile Phe Tyr Lys Ile
690 695 700
Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg Arg Asn Ala Asp
705 710 715 720
Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gln Ile Met Arg
725 730 735
Glu Tyr Ala Ser Asp Pro Glu Tyr Arg Lys His Leu Glu Ile Phe Tyr
740 745 750
Lys Ile Leu Thr Asn Thr Asp Pro Asn Asp Asp Val Glu Arg Arg Asn
755 760 765
Ala Asp Asn Lys Glu Asp Leu Thr Ser Ala Asp Pro Glu Gly Gln Ile
770 775 780
Met Arg Glu Tyr Ala Ala Asp Pro Glu Tyr Arg Lys His Leu Glu Val
785 790 795 800
Phe His Lys Ile Leu Thr Asn Thr Asp Pro Asn Asp Glu Val Glu Arg
805 810 815
Gln Asn Ala Asp Asn Asn Glu Ala
820
<210> 68
<211> 41
<212> PRT
<213> 恶性疟原虫
<400> 68
Gly Met Asn Asn Met Asn Gly Asp Ile Asn Asn Ile Asn Gly Asp Ile
1 5 10 15
Asn Asn Met Asn Gly Asp Ile Asn Asn Met Asn Gly Asp Ile Asn Asn
20 25 30
Met Asn Gly Asp Ile Asn Asn Met Asn
35 40
<210> 69
<211> 37
<212> PRT
<213> 恶性疟原虫
<400> 69
Glu Glu Ile Lys Glu Glu Ile Lys Glu Val Lys Glu Glu Ile Lys Glu
1 5 10 15
Val Lys Glu Glu Ile Lys Glu Val Lys Glu Glu Ile Lys Glu Val Lys
20 25 30
Glu Glu Ile Lys Glu
35
<210> 70
<211> 28
<212> PRT
<213> 恶性疟原虫
<400> 70
Glu Lys Leu Lys Lys Tyr Asn Asn Glu Ile Ser Ser Leu Lys Lys Glu
1 5 10 15
Leu Asp Ile Leu Asn Glu Lys Met Gly Lys Cys Thr
20 25
<210> 71
<211> 38
<212> PRT
<213> 恶性疟原虫
<400> 71
Thr Lys Lys Leu Asn Lys Glu Leu Ser Glu Gly Asn Lys Glu Leu Glu
1 5 10 15
Lys Leu Glu Lys Asn Ile Lys Glu Leu Glu Glu Thr Asn Asn Thr Leu
20 25 30
Glu Asn Asp Ile Lys Val
35
<210> 72
<211> 526
<212> PRT
<213> 恶性疟原虫
<400> 72
Met Ile Arg Ile Lys Lys Lys Leu Ile Leu Thr Ile Ile Tyr Ile His
1 5 10 15
Leu Phe Ile Leu Asn Arg Leu Ser Phe Glu Asn Ala Ile Lys Lys Thr
20 25 30
Lys Asn Gln Glu Asn Asn Leu Thr Leu Leu Pro Ile Lys Ser Thr Glu
35 40 45
Glu Glu Lys Asp Asp Ile Lys Asn Gly Lys Asp Ile Lys Lys Glu Ile
50 55 60
Asp Asn Asp Lys Glu Asn Ile Lys Thr Asn Asn Ala Lys Asp His Ser
65 70 75 80
Thr Tyr Ile Lys Ser Tyr Leu Asn Thr Asn Val Asn Asp Gly Leu Lys
85 90 95
Tyr Leu Phe Ile Pro Ser His Asn Ser Phe Ile Lys Lys Tyr Ser Val
100 105 110
Phe Asn Gln Ile Asn Asp Gly Met Leu Leu Asn Glu Lys Asn Asp Val
115 120 125
Lys Asn Asn Glu Asp Tyr Lys Asn Val Asp Tyr Lys Asn Val Asn Phe
130 135 140
Leu Gln Tyr His Phe Lys Glu Leu Ser Asn Tyr Asn Ile Ala Asn Ser
145 150 155 160
Ile Asp Ile Leu Gln Glu Lys Glu Gly His Leu Asp Phe Val Ile Ile
165 170 175
Pro His Tyr Thr Phe Leu Asp Tyr Tyr Lys His Leu Ser Tyr Asn Ser
180 185 190
Ile Tyr His Lys Ser Ser Thr Tyr Gly Lys Cys Ile Ala Val Asp Ala
195 200 205
Phe Ile Lys Lys Ile Asn Glu Thr Tyr Asp Lys Val Lys Ser Lys Cys
210 215 220
Asn Asp Ile Lys Asn Asp Leu Ile Ala Thr Ile Lys Lys Leu Glu His
225 230 235 240
Pro Tyr Asp Ile Asn Asn Lys Asn Asp Asp Ser Tyr Arg Tyr Asp Ile
245 250 255
Ser Glu Glu Ile Asp Asp Lys Ser Glu Glu Thr Asp Asp Glu Thr Glu
260 265 270
Glu Val Glu Asp Ser Ile Gln Asp Thr Asp Ser Asn His Thr Pro Ser
275 280 285
Asn Lys Lys Lys Asn Asp Leu Met Asn Arg Thr Phe Lys Lys Met Met
290 295 300
Asp Glu Tyr Asn Thr Lys Lys Lys Lys Leu Ile Lys Cys Ile Lys Asn
305 310 315 320
His Glu Asn Asp Phe Asn Lys Ile Cys Met Asp Met Lys Asn Tyr Gly
325 330 335
Thr Asn Leu Phe Glu Gln Leu Ser Cys Tyr Asn Asn Asn Phe Cys Asn
340 345 350
Thr Asn Gly Ile Arg Tyr His Tyr Asp Glu Tyr Ile His Lys Leu Ile
355 360 365
Leu Ser Val Lys Ser Lys Asn Leu Asn Lys Asp Leu Ser Asp Met Thr
370 375 380
Asn Ile Leu Gln Gln Ser Glu Leu Leu Leu Thr Asn Leu Asn Lys Lys
385 390 395 400
Met Gly Ser Tyr Ile Tyr Ile Asp Thr Ile Lys Phe Ile His Lys Glu
405 410 415
Met Lys His Ile Phe Asn Arg Ile Glu Tyr His Thr Lys Ile Ile Asn
420 425 430
Asp Lys Thr Lys Ile Ile Gln Asp Lys Ile Lys Leu Asn Ile Trp Arg
435 440 445
Thr Phe Gln Lys Asp Glu Leu Leu Lys Arg Ile Leu Asp Met Ser Asn
450 455 460
Glu Tyr Ser Leu Phe Ile Thr Ser Asp His Leu Arg Gln Met Leu Tyr
465 470 475 480
Asn Thr Phe Tyr Ser Lys Glu Lys His Leu Asn Asn Ile Phe His His
485 490 495
Leu Ile Tyr Val Leu Gln Met Lys Phe Asn Asp Val Pro Ile Lys Met
500 505 510
Glu Tyr Phe Gln Thr Tyr Lys Lys Asn Lys Pro Leu Thr Gln
515 520 525
<210> 73
<211> 622
<212> PRT
<213> 恶性疟原虫
<400> 73
Met Arg Lys Leu Tyr Cys Val Leu Leu Leu Ser Ala Phe Glu Phe Thr
1 5 10 15
Tyr Met Ile Asn Phe Gly Arg Gly Gln Asn Tyr Trp Glu His Pro Tyr
20 25 30
Gln Asn Ser Asp Val Tyr Arg Pro Ile Asn Glu His Arg Glu His Pro
35 40 45
Lys Glu Tyr Glu Tyr Pro Leu His Gln Glu His Thr Tyr Gln Gln Glu
50 55 60
Asp Ser Gly Glu Asp Glu Asn Thr Leu Gln His Ala Tyr Pro Ile Asp
65 70 75 80
His Glu Gly Ala Glu Pro Ala Pro Gln Glu Gln Asn Leu Phe Ser Ser
85 90 95
Ile Glu Ile Val Glu Arg Ser Asn Tyr Met Gly Asn Pro Trp Thr Glu
100 105 110
Tyr Met Ala Lys Tyr Asp Ile Glu Glu Val His Gly Ser Gly Ile Arg
115 120 125
Val Asp Leu Gly Glu Asp Ala Glu Val Ala Gly Thr Gln Tyr Arg Leu
130 135 140
Pro Ser Gly Lys Cys Pro Val Phe Gly Lys Gly Ile Ile Ile Glu Asn
145 150 155 160
Ser Asn Thr Thr Phe Leu Thr Pro Val Ala Thr Gly Asn Gln Tyr Leu
165 170 175
Lys Asp Gly Gly Phe Ala Phe Pro Pro Thr Glu Pro Leu Met Ser Pro
180 185 190
Met Thr Leu Asp Glu Met Arg His Phe Tyr Lys Asp Asn Lys Tyr Val
195 200 205
Lys Asn Leu Asp Glu Leu Thr Leu Cys Ser Arg His Ala Gly Asn Met
210 215 220
Ile Pro Asp Asn Asp Lys Asn Ser Asn Tyr Lys Tyr Pro Ala Val Tyr
225 230 235 240
Asp Asp Lys Asp Lys Lys Cys His Ile Leu Tyr Ile Ala Ala Gln Glu
245 250 255
Asn Asn Gly Pro Arg Tyr Cys Asn Lys Asp Glu Ser Lys Arg Asn Ser
260 265 270
Met Phe Cys Phe Arg Pro Ala Lys Asp Ile Ser Phe Gln Asn Tyr Thr
275 280 285
Tyr Leu Ser Lys Asn Val Val Asp Asn Trp Glu Lys Val Cys Pro Arg
290 295 300
Lys Asn Leu Gln Asn Ala Lys Phe Gly Leu Trp Val Asp Gly Asn Cys
305 310 315 320
Glu Asp Ile Pro His Val Asn Glu Phe Pro Ala Ile Asp Leu Phe Glu
325 330 335
Cys Asn Lys Leu Val Phe Glu Leu Ser Ala Ser Asp Gln Pro Lys Gln
340 345 350
Tyr Glu Gln His Leu Thr Asp Tyr Glu Lys Ile Lys Glu Gly Phe Lys
355 360 365
Asn Lys Asn Ala Ser Met Ile Lys Ser Ala Phe Leu Pro Thr Gly Ala
370 375 380
Phe Lys Ala Asp Arg Tyr Lys Ser His Gly Lys Gly Tyr Asn Trp Gly
385 390 395 400
Asn Tyr Asn Thr Glu Thr Gln Lys Cys Glu Ile Phe Asn Val Lys Pro
405 410 415
Thr Cys Leu Ile Asn Asn Ser Ser Tyr Ile Ala Thr Thr Ala Leu Ser
420 425 430
His Pro Ile Glu Val Glu Asn Asn Phe Pro Cys Ser Leu Tyr Lys Asp
435 440 445
Glu Ile Met Lys Glu Ile Glu Arg Glu Ser Lys Arg Ile Lys Leu Asn
450 455 460
Asp Asn Asp Asp Glu Gly Asn Lys Lys Ile Ile Ala Pro Arg Ile Phe
465 470 475 480
Ile Ser Asp Asp Lys Asp Ser Leu Lys Cys Pro Cys Asp Pro Glu Met
485 490 495
Val Ser Asn Ser Thr Cys Arg Phe Phe Val Cys Lys Cys Val Glu Arg
500 505 510
Arg Ala Glu Val Thr Ser Asn Asn Glu Val Val Val Lys Glu Glu Tyr
515 520 525
Lys Asp Glu Tyr Ala Asp Ile Pro Glu His Lys Pro Thr Tyr Asp Lys
530 535 540
Met Lys Ile Ile Ile Ala Ser Ser Ala Ala Val Ala Val Leu Ala Thr
545 550 555 560
Ile Leu Met Val Tyr Leu Tyr Lys Arg Lys Gly Asn Ala Glu Lys Tyr
565 570 575
Asp Lys Met Asp Glu Pro Gln Asp Tyr Gly Lys Ser Asn Ser Arg Asn
580 585 590
Asp Glu Met Leu Asp Pro Glu Ala Ser Phe Trp Gly Glu Glu Lys Arg
595 600 605
Ala Ser His Thr Thr Pro Val Leu Met Glu Lys Pro Tyr Tyr
610 615 620
<210> 74
<211> 217
<212> PRT
<213> 恶性疟原虫
<400> 74
Met Asn Lys Leu Tyr Ser Leu Phe Leu Phe Leu Phe Ile Gln Leu Ser
1 5 10 15
Ile Lys Tyr Asn Asn Ala Lys Val Thr Val Asp Thr Val Cys Lys Arg
20 25 30
Gly Phe Leu Ile Gln Met Ser Gly His Leu Glu Cys Lys Cys Glu Asn
35 40 45
Asp Leu Val Leu Val Asn Glu Glu Thr Cys Glu Glu Lys Val Leu Lys
50 55 60
Cys Asp Glu Lys Thr Val Asn Lys Pro Cys Gly Asp Phe Ser Lys Cys
65 70 75 80
Ile Lys Ile Asp Gly Asn Pro Val Ser Tyr Ala Cys Lys Cys Asn Leu
85 90 95
Gly Tyr Asp Met Val Asn Asn Val Cys Ile Pro Asn Glu Cys Lys Asn
100 105 110
Val Thr Cys Gly Asn Gly Lys Cys Ile Leu Asp Thr Ser Asn Pro Val
115 120 125
Lys Thr Gly Val Cys Ser Cys Asn Ile Gly Lys Val Pro Asn Val Gln
130 135 140
Asp Gln Asn Lys Cys Ser Lys Asp Gly Glu Thr Lys Cys Ser Leu Lys
145 150 155 160
Cys Leu Lys Glu Asn Glu Thr Cys Lys Ala Val Asp Gly Ile Tyr Lys
165 170 175
Cys Asp Cys Lys Asp Gly Phe Ile Ile Asp Asn Glu Ser Ser Ile Cys
180 185 190
Thr Ala Phe Ser Ala Tyr Asn Ile Leu Asn Leu Ser Ile Met Phe Ile
195 200 205
Leu Phe Ser Val Cys Phe Phe Ile Met
210 215
<210> 75
<211> 2163
<212> PRT
<213> 恶性疟原虫
<400> 75
Met Val Thr Gln Ser Ser Gly Gly Gly Ala Ala Gly Ser Ser Gly Glu
1 5 10 15
Glu Asp Ala Lys His Val Leu Asp Glu Phe Gly Gln Gln Val Tyr Asn
20 25 30
Glu Lys Val Glu Lys Tyr Ala Asn Ser Lys Ile Tyr Lys Glu Ala Leu
35 40 45
Lys Gly Asp Leu Ser Gln Ala Ser Ile Leu Ser Glu Leu Ala Gly Thr
50 55 60
Tyr Lys Pro Cys Ala Leu Glu Tyr Glu Tyr Tyr Lys His Thr Asn Gly
65 70 75 80
Gly Gly Lys Gly Lys Arg Tyr Pro Cys Thr Glu Leu Gly Glu Lys Val
85 90 95
Glu Pro Arg Phe Ser Asp Thr Leu Gly Gly Gln Cys Thr Asn Lys Lys
100 105 110
Ile Glu Gly Asn Lys Tyr Ile Lys Gly Lys Asp Val Gly Ala Cys Ala
115 120 125
Pro Tyr Arg Arg Leu His Leu Cys Ser His Asn Leu Glu Ser Ile Gln
130 135 140
Thr Asn Asn Tyr Asn Ser Gly Asn Ala Lys His Asn Leu Leu Val Asp
145 150 155 160
Val Cys Met Ala Ala Lys Tyr Glu Gly Asp Ser Ile Lys Asn Tyr Tyr
165 170 175
Pro Lys Tyr Gln Arg Thr Tyr Pro Asp Thr Asn Ser Gln Leu Cys Thr
180 185 190
Val Leu Ala Arg Ser Phe Ala Asp Ile Gly Asp Ile Val Arg Gly Lys
195 200 205
Asp Leu Tyr Leu Gly Asn Pro Gln Glu Ser Thr Gln Arg Ile Ile Leu
210 215 220
Glu Asn Asn Leu Lys Asp Ile Phe Ala Lys Ile His Ser Asp Val Met
225 230 235 240
Ser Thr Ser Gly Ser Asn Gly Arg Ala Leu Gln Lys Arg Tyr Lys Asp
245 250 255
Thr Asp Asn Tyr Tyr Glu Leu Arg Glu Asp Trp Trp Ala Leu Asn Arg
260 265 270
Asp Gln Val Trp Lys Ala Ile Thr Cys Asn Ala Gly Gly Gly Asn Arg
275 280 285
Tyr Phe Arg Gln Thr Cys Gly Ser Gly Glu Trp Ala Lys Asp Lys Cys
290 295 300
Arg Cys Lys Asp Asp Lys Val Pro Thr Tyr Phe Asp Tyr Val Pro Gln
305 310 315 320
Tyr Leu Arg Trp Phe Glu Glu Trp Ala Glu Asp Phe Cys Arg Leu Arg
325 330 335
Lys His Lys Leu Lys Asp Ala Lys Asn Lys Cys Arg Gly Asp Ser Gly
340 345 350
Asn Asp Arg Tyr Cys Asp Leu Asn Arg Tyr Asp Cys Thr Gln Thr Ile
355 360 365
Arg Gly Asn Glu His Phe Val Glu Lys Asp Asp Cys Lys Gly Cys Gln
370 375 380
Tyr Ser Cys Ala His Phe Val Asn Trp Ile Asp Asn Gln Lys Leu Glu
385 390 395 400
Phe Glu Lys Gln Lys Glu Lys Tyr Thr Lys Glu Ile Lys Lys Lys His
405 410 415
Pro Thr Thr Ile Ile Ile Lys Thr Ala Asn Arg Lys Thr Thr Ile Asn
420 425 430
Asn Leu Tyr Val Lys Glu Phe Tyr Lys Lys Leu Gln Glu Lys Tyr Gly
435 440 445
Asp Val Glu Asn Phe Leu Gln Lys Leu Asn Glu Glu Gln Ile Cys Lys
450 455 460
Asn Gln Pro Tyr Asn Asp Glu Ser Ser Ile Asp Ile Asn Phe Lys Ser
465 470 475 480
Ile Lys Asp Ile Asp Ile Phe Ser His Thr Glu Tyr Cys Gln Ala Cys
485 490 495
Pro Trp Cys Gly Ala Lys Arg Lys Gly Lys Gly Trp Glu Pro Lys Glu
500 505 510
Lys Thr Cys Gly Lys Thr Lys Thr Tyr Asp Pro Lys Lys Thr Thr Asn
515 520 525
Ile Pro Ile Leu Thr Pro Tyr Ile Ser Gln Gln Ser Ile Leu Lys Lys
530 535 540
Tyr Asn Lys Phe Cys Asn Gly Asn Gly Gly Asn Gly Ala Pro Ala Thr
545 550 555 560
Ala Thr Gly Gly Gly Gln Ile Lys Asn Trp Gln Cys His Tyr Glu Gly
565 570 575
Asp Asn Asn Asp Asn Cys Val Glu Gly Glu Trp Lys Glu Phe Lys Glu
580 585 590
Gly Lys Asn Val Met Ser Tyr Asn Ala Phe Phe Trp Lys Trp Val His
595 600 605
Asp Met Leu Ile Asp Ser Met Gln Trp Arg Asn Glu His Gly Asn Cys
610 615 620
Ile Asn Lys Asp Asn Asp Asn Thr Cys Lys Asn Ser Cys Lys Arg Pro
625 630 635 640
Cys Glu Cys Phe Lys Arg Trp Val Asp Gln Lys Lys Lys Asn Glu Trp
645 650 655
Glu Ala Ile Lys Asp His Phe Lys Lys Gln Asn Ile Ala Ala Glu Thr
660 665 670
Gln Cys Asp Pro Gly Val Thr Leu Gln Trp Val Leu Ile Leu Asp Phe
675 680 685
Leu Lys Asp Glu Ser Thr Glu Asp Lys Glu Asn Lys Val Ser Ala Glu
690 695 700
Glu Ala Lys Glu Ile Lys His Leu Arg Gln Met Leu Gln Gln Ala Gly
705 710 715 720
Val Asp Asp Pro Ala Ala Phe Ala Arg Pro Cys Thr Glu Asp Gly Val
725 730 735
Ala Glu Gln Asp Thr Ile Met Asp Lys Leu Leu Asn Arg Glu Glu Asn
740 745 750
Asp Ala Thr Glu Cys Lys Lys Cys Asp Lys Pro Pro Pro Ala Pro Thr
755 760 765
Ala Gly Asp Arg Gly Pro Gly Ala Arg Ala Asp Pro His Asp Val Gln
770 775 780
Gln Pro Arg Pro Pro Gly Ser Gly Pro Gly Thr Asp Ala Asn Asp Glu
785 790 795 800
Asp Asp Asp Asp Asp Asp Asp Asp Asp Asp Glu Glu Asp Gly Glu Ala
805 810 815
Lys Glu Glu Glu Glu Asp Glu Glu Lys Gln Glu Asp Val His Gln Glu
820 825 830
Glu Lys Ala Lys Lys Glu Glu Pro Gln Lys Glu Glu Val Ala Arg Thr
835 840 845
Pro Lys Asp Asp Val Asn Val Cys Asn Ile Val Asn Asn Val Phe Thr
850 855 860
Asp Gly Ser Ser Leu Gln Ala Ala Cys Ser Leu Lys Tyr Gly Lys Asn
865 870 875 880
Ala Pro Thr Ser Trp Lys Cys Val Thr Pro Ser Gly Asn Thr Ser Asp
885 890 895
Thr Thr Val Lys Ser Gly Asp Thr Thr Gly Gly Ser Ile Cys Val Pro
900 905 910
Pro Arg Arg Arg Arg Leu Tyr Val Thr Pro Leu Thr Arg Leu Thr Gly
915 920 925
Gly Asp Ser Thr Thr Gln Ala Ser Gln Ala Ser Glu Val Gln Thr Gln
930 935 940
Ala Arg Gly Ser Asn Thr Asp Lys Ser Pro Gly Ser Ser Glu Ala Ala
945 950 955 960
Gln Gly Asp Gly Val Ser Lys Asp Pro Gln Lys Ala Leu Leu Lys Ala
965 970 975
Phe Val Glu Ser Ala Ala Val Glu Thr Phe Phe Leu Trp Asp Arg Tyr
980 985 990
Lys Lys Ile Lys Glu Lys Glu Lys Lys Glu Lys Lys Lys Thr Tyr Glu
995 1000 1005
Gln Ile Tyr Glu Ser Thr Asp Tyr Asp Asp Glu Glu Lys Asp Pro
1010 1015 1020
Gln Glu Glu Leu Lys Lys Gly Ile Ile Pro Asp Glu Phe Lys Arg
1025 1030 1035
Gln Met Phe Tyr Thr Leu Gly Asp Tyr Lys Asp Ile Leu Tyr Ser
1040 1045 1050
Gly Asp Thr Val Asn Gly Gly Asn Glu Asp Lys Ile Lys Lys Ala
1055 1060 1065
Ile Asn Asn Tyr Phe Gln Lys Ile Arg Glu Gln Ser Ser Ser Asp
1070 1075 1080
Asn Asn Pro Ser Pro Arg Ser Val Lys Thr Pro Ser Thr Ser Asp
1085 1090 1095
Lys Asp Pro Gln Thr Trp Trp Asn Ala His Ala Pro Ser Ile Trp
1100 1105 1110
Asn Ala Met Val Cys Ala Leu Thr Tyr Asp Thr Asn Ser Gly Gly
1115 1120 1125
Glu Gly Lys Thr Thr Thr Ile Thr Gln Asp Pro Asn Leu Lys Thr
1130 1135 1140
Ala Leu Trp Asp Glu Asn Gly Lys Lys Pro Leu Lys Thr Lys Tyr
1145 1150 1155
Gln Tyr Asp Ser Val Thr Ile Gly Ala Ser Gly Ala Lys Pro Gln
1160 1165 1170
Thr Lys Ala Lys Pro Thr Gly Gly Asp Thr Pro Leu Thr Gln Phe
1175 1180 1185
Val Leu Arg Pro Thr Tyr Phe Arg Tyr Leu Glu Glu Trp Gly Gln
1190 1195 1200
Asn Phe Cys Lys Lys Arg Thr Glu Met Leu Glu Lys Ile Lys Tyr
1205 1210 1215
Glu Cys Lys Val Gly Gln Gly Arg Gly Gly Arg Lys Gln Lys Thr
1220 1225 1230
Pro Gln Cys Ser Cys Tyr Gly Glu Asn Cys Asp Asp Gln Leu Asp
1235 1240 1245
Asp Asn Pro Ser Thr Asp Ala Asp Leu Lys Cys Pro Gly Cys Gly
1250 1255 1260
Arg Glu Cys Arg Lys Tyr Lys Lys Trp Ile Glu Lys Lys Lys Glu
1265 1270 1275
Glu Phe Thr Lys Gln Ser Asn Val Tyr Glu Glu Gln Lys Thr Lys
1280 1285 1290
Cys Gln Lys Glu Ser Lys Ser Ala Lys Gly Asn Asn His Gly Asn
1295 1300 1305
Glu Phe Cys Gly Thr Gln Gly Thr Cys Asp Thr Ala Gly Asp Phe
1310 1315 1320
Leu Asn Arg Leu Lys Ser Gly Pro Cys Lys Lys Glu Asn Gly Lys
1325 1330 1335
Asp Asn Gln Glu Asp Glu Ile Asn Phe Lys Asp Glu Asp Lys Thr
1340 1345 1350
Phe Gly His Glu Asn Tyr Cys Ala Pro Cys Pro Val Phe Lys Asp
1355 1360 1365
Ile Cys Lys Lys Lys Asp Cys Arg Asn Ala Ser Asn Asn Met Cys
1370 1375 1380
Asn Gly Lys Asp Phe Ile Thr Ala Glu Asp Ile Lys Ile Met Asp
1385 1390 1395
Ser Ser Ser Glu Glu Val Asn Met Leu Val Ser Asp Asn Asp Thr
1400 1405 1410
Asn Lys Phe Asp Gly Gly Leu Asp Ala Cys Lys Asp Ala His Ile
1415 1420 1425
Phe Lys Gly Ile Lys Glu Asn Lys Trp Ser Cys Gly Asn Val Cys
1430 1435 1440
Gly Tyr Asn Val Cys Lys Pro Lys Lys Val Asn Gly Glu Lys Gly
1445 1450 1455
Ser Gly Glu Asn Asn Asp Gln Ile Ile Thr Ile Arg Gly Leu Val
1460 1465 1470
Thr His Trp Val Gln Asn Phe Leu Asp Asp Tyr Asn Lys Ile Arg
1475 1480 1485
Thr Lys Leu Lys Pro Cys Arg Asn Asn Gly Glu Val Ser Lys Cys
1490 1495 1500
Ile Lys Asp Cys Val Lys Lys Trp Val Glu Lys Lys Thr Glu Glu
1505 1510 1515
Trp Pro Lys Ile Arg Asp Arg Tyr Leu Glu Pro Tyr Lys Ser Asp
1520 1525 1530
Asp Gly Tyr Asn Lys Lys Ser Leu Val Arg Ser Phe Met Glu Thr
1535 1540 1545
Leu Ile Pro Leu Met Asp Leu Thr Asn Gly Lys Glu Lys Ile Gln
1550 1555 1560
Glu Leu Asn Lys Phe Leu Arg Ser Tyr Glu Cys Asn Cys Ala Asp
1565 1570 1575
Asn Ser Gln Gln Lys Gly Asp Thr Pro Lys Asp Ile Val Glu Cys
1580 1585 1590
Leu Leu Glu Lys Leu Glu Asp Lys Ala Asn Lys Cys Lys Thr Gln
1595 1600 1605
Thr Ser Gly Thr Asp Cys His Pro Ser Thr Pro Leu Glu Asp Asp
1610 1615 1620
Asp Glu Pro Leu Glu Glu Thr Glu Glu Asn Thr Val Glu Gln Pro
1625 1630 1635
Asn Ile Cys Pro Thr Lys Gln Pro Gln Pro Glu Lys Glu Asp Gly
1640 1645 1650
Cys Glu Ala Ala Pro Thr Thr Ala Glu Glu Thr Ser Pro Thr Ala
1655 1660 1665
Thr Ser Glu Gly Thr Glu Asn Gln Ser Pro Pro Pro Pro Pro Pro
1670 1675 1680
Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Glu Lys Ser Gln Pro
1685 1690 1695
Lys Glu Asp Lys Lys Val Glu Pro Gln Pro Lys Pro Gln Pro Thr
1700 1705 1710
Asn Pro Pro Pro Asn Leu Phe Asn Asn Pro Ala Val Ile Pro Ala
1715 1720 1725
Leu Met Ser Ser Thr Ile Met Trp Ser Ile Gly Ile Gly Phe Ala
1730 1735 1740
Ala Phe Thr Tyr Phe Leu Leu Lys Lys Lys Thr Lys Ser Ser Val
1745 1750 1755
Gly Asn Leu Phe Gln Ile Leu Gln Ile Pro Gln Asn Asp Tyr Gly
1760 1765 1770
Ile Pro Thr Leu Lys Ser Lys Asn Arg Tyr Ile Pro Tyr Arg Ser
1775 1780 1785
Gly Thr Tyr Lys Gly Lys Thr Tyr Ile Tyr Met Glu Gly Asp Ser
1790 1795 1800
Ser Gly Asp Glu Lys Tyr Ala Phe Met Ser Asp Thr Thr Asp Val
1805 1810 1815
Thr Ser Ser Glu Ser Glu Tyr Glu Glu Leu Asp Ile Asn Asp Ile
1820 1825 1830
Tyr Val Pro His Ala Pro Lys Tyr Lys Thr Leu Ile Glu Val Val
1835 1840 1845
Leu Glu Pro Ser Gly Asn Asn Thr Thr Ala Ser Gly Lys Asn Thr
1850 1855 1860
Pro Ser Asp Thr Gln Asn Asp Ile Pro Thr Ser Asp Thr Pro Pro
1865 1870 1875
Pro Ile Thr Asp Asn Glu Trp Asn Thr Leu Lys Asp Glu Phe Ile
1880 1885 1890
Ser Gln Tyr Leu Gln Ser Glu Gln Pro Lys Asp Val Pro Asn Asp
1895 1900 1905
Tyr Lys Ser Gly Asp Ile Pro Leu Asn Thr Gln Pro Asn Thr Leu
1910 1915 1920
Tyr Phe Asn Lys Pro Glu Glu Lys Pro Phe Ile Thr Ser Ile His
1925 1930 1935
Asp Arg Asp Leu Tyr Thr Gly Glu Gln Ile Ser Tyr Asn Ile His
1940 1945 1950
Met Ser Thr Asn Thr Met Asp Asp Pro Lys Tyr Val Ser Asn Asn
1955 1960 1965
Val Tyr Ser Gly Ile Asp Leu Ile Asn Asp Ala Leu Asn Gly Asp
1970 1975 1980
Tyr Asp Ile Tyr Asp Glu Ile Leu Lys Arg Lys Glu Asn Glu Leu
1985 1990 1995
Phe Gly Thr Asn His Val Lys Gln Thr Ser Ile His Ser Val Ala
2000 2005 2010
Lys Leu Thr Asn Ser Asp Pro Ile His Asn Gln Leu Glu Leu Phe
2015 2020 2025
His Lys Trp Leu Asp Arg His Arg Asn Met Cys Glu Lys Trp Lys
2030 2035 2040
Asn Asp Asn Glu Arg Leu Ala Lys Leu Lys Glu Glu Trp Glu Asn
2045 2050 2055
Glu Thr His Ser Gly Asn Thr His Pro Ser Asp Ser Asn Lys Thr
2060 2065 2070
Leu Asn Thr Asp Val Ser Ile Gln Ile Asp Met Asp His Glu Lys
2075 2080 2085
Arg Met Lys Glu Phe Thr Asn Met Asp Thr Ile Leu Asp Asp Leu
2090 2095 2100
Lys Thr Tyr Asn Glu Pro Tyr Tyr Asp Val Gln Asp Asp Ile Tyr
2105 2110 2115
Tyr Asp Val Asn Asp His Asp Ala Ser Thr Val Asp Ser Asn Asn
2120 2125 2130
Met Asp Val Pro Ser Arg Val Gln Ile Glu Met Asp Val Asn Thr
2135 2140 2145
Lys Leu Val Lys Glu Lys Tyr Pro Ile Ala Asp Val Trp Asp Ile
2150 2155 2160
<210> 76
<211> 1558
<212> PRT
<213> 恶性疟原虫
<400> 76
Met Thr Asn Ser Asn Tyr Lys Ser Asn Asn Lys Thr Tyr Asn Glu Asn
1 5 10 15
Asn Asn Glu Gln Ile Thr Thr Ile Phe Asn Arg Thr Asn Met Asn Pro
20 25 30
Ile Lys Lys Cys His Met Arg Glu Lys Ile Asn Lys Tyr Phe Phe Leu
35 40 45
Ile Lys Ile Leu Thr Cys Thr Ile Leu Ile Trp Ala Val Gln Tyr Ala
50 55 60
Asn Asn Ser Asp Ile Asn Lys Ser Trp Lys Lys Asn Thr Tyr Val Asp
65 70 75 80
Lys Lys Leu Asn Lys Leu Phe Asn Arg Ser Leu Gly Glu Ser Gln Val
85 90 95
Asn Gly Glu Leu Ala Ser Glu Glu Val Lys Glu Lys Ile Leu Asp Leu
100 105 110
Leu Glu Glu Gly Asn Thr Leu Thr Glu Ser Val Asp Asp Asn Lys Asn
115 120 125
Leu Glu Glu Ala Glu Asp Ile Lys Glu Asn Ile Leu Leu Ser Asn Ile
130 135 140
Glu Glu Pro Lys Glu Asn Ile Ile Asp Asn Leu Leu Asn Asn Ile Gly
145 150 155 160
Gln Asn Ser Glu Lys Gln Glu Ser Val Ser Glu Asn Val Gln Val Ser
165 170 175
Asp Glu Leu Phe Asn Glu Leu Leu Asn Ser Val Asp Val Asn Gly Glu
180 185 190
Val Lys Glu Asn Ile Leu Glu Glu Ser Gln Val Asn Asp Asp Ile Phe
195 200 205
Asn Ser Leu Val Lys Ser Val Gln Gln Glu Gln Gln His Asn Val Glu
210 215 220
Glu Lys Val Glu Glu Ser Val Glu Glu Asn Asp Glu Glu Ser Val Glu
225 230 235 240
Glu Asn Val Glu Glu Asn Val Glu Glu Asn Asp Asp Glu Ser Val Ala
245 250 255
Ser Ser Val Glu Glu Ser Ile Ala Ser Ser Val Asp Glu Ser Ile Asp
260 265 270
Ser Ser Ile Glu Glu Asn Val Ala Pro Thr Val Glu Glu Ile Val Ala
275 280 285
Pro Thr Val Glu Glu Ile Val Ala Pro Ser Val Val Glu Ser Val Ala
290 295 300
Pro Ser Val Glu Glu Ser Val Glu Glu Asn Val Glu Glu Ser Val Ala
305 310 315 320
Glu Asn Val Glu Glu Ser Val Ala Glu Asn Val Glu Glu Ser Val Ala
325 330 335
Glu Asn Val Glu Glu Ser Val Ala Glu Asn Val Glu Glu Ser Val Ala
340 345 350
Glu Asn Val Glu Glu Ser Val Ala Glu Asn Val Glu Glu Ile Val Ala
355 360 365
Pro Thr Val Glu Glu Ser Val Ala Pro Thr Val Glu Glu Ile Val Ala
370 375 380
Pro Ser Val Glu Glu Ser Val Ala Pro Ser Val Glu Glu Ile Val Val
385 390 395 400
Pro Thr Val Glu Glu Ser Val Ala Glu Asn Val Glu Glu Ile Val Ala
405 410 415
Pro Ser Val Glu Glu Ile Val Ala Pro Ser Val Glu Glu Ile Val Ala
420 425 430
Pro Thr Val Glu Glu Ser Val Ala Pro Thr Val Glu Glu Ile Val Ala
435 440 445
Pro Ser Val Glu Glu Ser Val Ala Pro Ser Val Glu Glu Ile Val Val
450 455 460
Pro Thr Val Glu Glu Ser Val Ala Glu Asn Val Glu Glu Ser Val Ala
465 470 475 480
Glu Asn Val Glu Glu Ile Val Ala Pro Ser Val Glu Glu Ile Val Ala
485 490 495
Pro Ser Val Glu Glu Ile Val Ala Pro Ser Val Glu Glu Ile Val Ala
500 505 510
Pro Ser Val Glu Glu Ile Val Ala Pro Ser Val Glu Glu Ile Val Ala
515 520 525
Pro Ser Val Glu Glu Ile Val Ala Pro Ser Val Glu Glu Ile Val Ala
530 535 540
Pro Ser Val Glu Glu Ile Val Ala Pro Thr Val Glu Glu Ile Val Ala
545 550 555 560
Pro Thr Val Glu Glu Ile Val Ala Pro Ser Val Glu Glu Ile Val Ala
565 570 575
Pro Thr Val Glu Glu Ser Val Ala Glu Asn Val Ala Thr Asn Leu Ser
580 585 590
Asp Asn Leu Leu Ser Asn Leu Leu Gly Gly Ile Glu Thr Glu Glu Ile
595 600 605
Lys Asp Ser Ile Leu Asn Glu Ile Glu Glu Val Lys Glu Asn Val Val
610 615 620
Thr Thr Ile Leu Glu Asn Val Glu Glu Thr Thr Ala Glu Ser Val Thr
625 630 635 640
Thr Phe Ser Asn Ile Leu Glu Glu Ile Gln Glu Asn Thr Ile Thr Asn
645 650 655
Asp Thr Ile Glu Glu Lys Leu Glu Glu Leu His Glu Asn Val Leu Ser
660 665 670
Ala Ala Leu Glu Asn Thr Gln Ser Glu Glu Glu Lys Lys Glu Val Ile
675 680 685
Asp Val Ile Glu Glu Val Lys Glu Glu Val Ala Thr Thr Leu Ile Glu
690 695 700
Thr Val Glu Gln Ala Glu Glu Glu Ser Ala Ser Thr Ile Thr Glu Ile
705 710 715 720
Phe Glu Asn Leu Glu Glu Asn Ala Val Glu Ser Asn Glu Asn Val Ala
725 730 735
Glu Asn Leu Glu Lys Leu Asn Glu Thr Val Phe Asn Thr Val Leu Asp
740 745 750
Lys Val Glu Glu Thr Val Glu Ile Ser Gly Glu Ser Leu Glu Asn Asn
755 760 765
Glu Met Asp Lys Ala Phe Phe Ser Glu Ile Phe Asp Asn Val Lys Gly
770 775 780
Ile Gln Glu Asn Leu Leu Thr Gly Met Phe Arg Ser Ile Glu Thr Ser
785 790 795 800
Ile Val Ile Gln Ser Glu Glu Lys Val Asp Leu Asn Glu Asn Val Val
805 810 815
Ser Ser Ile Leu Asp Asn Ile Glu Asn Met Lys Glu Gly Leu Leu Asn
820 825 830
Lys Leu Glu Asn Ile Ser Ser Thr Glu Gly Val Gln Glu Thr Val Thr
835 840 845
Glu His Val Glu Gln Asn Val Tyr Val Asp Val Asp Val Pro Ala Met
850 855 860
Lys Asp Gln Phe Leu Gly Ile Leu Asn Glu Ala Gly Gly Leu Lys Glu
865 870 875 880
Met Phe Phe Asn Leu Glu Asp Val Phe Lys Ser Glu Ser Asp Val Ile
885 890 895
Thr Val Glu Glu Ile Lys Asp Glu Pro Val Gln Lys Glu Val Glu Lys
900 905 910
Glu Thr Val Ser Ile Ile Glu Glu Met Glu Glu Asn Ile Val Asp Val
915 920 925
Leu Glu Glu Glu Lys Glu Asp Leu Thr Asp Lys Met Ile Asp Ala Val
930 935 940
Glu Glu Ser Ile Glu Ile Ser Ser Asp Ser Lys Glu Glu Thr Glu Ser
945 950 955 960
Ile Lys Asp Lys Glu Lys Asp Val Ser Leu Val Val Glu Glu Val Gln
965 970 975
Asp Asn Asp Met Asp Glu Ser Val Glu Lys Val Leu Glu Leu Lys Asn
980 985 990
Met Glu Glu Glu Leu Met Lys Asp Ala Val Glu Ile Asn Asp Ile Thr
995 1000 1005
Ser Lys Leu Ile Glu Glu Thr Gln Glu Leu Asn Glu Val Glu Ala
1010 1015 1020
Asp Leu Ile Lys Asp Met Glu Lys Leu Lys Glu Leu Glu Lys Ala
1025 1030 1035
Leu Ser Glu Asp Ser Lys Glu Ile Ile Asp Ala Lys Asp Asp Thr
1040 1045 1050
Leu Glu Lys Val Ile Glu Glu Glu His Asp Ile Thr Thr Thr Leu
1055 1060 1065
Asp Glu Val Val Glu Leu Lys Asp Val Glu Glu Asp Lys Ile Glu
1070 1075 1080
Lys Val Ser Asp Leu Lys Asp Leu Glu Glu Asp Ile Leu Lys Glu
1085 1090 1095
Val Lys Glu Ile Lys Glu Leu Glu Ser Glu Ile Leu Glu Asp Tyr
1100 1105 1110
Lys Glu Leu Lys Thr Ile Glu Thr Asp Ile Leu Glu Glu Lys Lys
1115 1120 1125
Glu Ile Glu Lys Asp His Phe Glu Lys Phe Glu Glu Glu Ala Glu
1130 1135 1140
Glu Ile Lys Asp Leu Glu Ala Asp Ile Leu Lys Glu Val Ser Ser
1145 1150 1155
Leu Glu Val Glu Glu Glu Lys Lys Leu Glu Glu Val His Glu Leu
1160 1165 1170
Lys Glu Glu Val Glu His Ile Ile Ser Gly Asp Ala His Ile Lys
1175 1180 1185
Gly Leu Glu Glu Asp Asp Leu Glu Glu Val Asp Asp Leu Lys Gly
1190 1195 1200
Ser Ile Leu Asp Met Leu Lys Gly Asp Met Glu Leu Gly Asp Met
1205 1210 1215
Asp Lys Glu Ser Leu Glu Asp Val Thr Ala Lys Leu Gly Glu Arg
1220 1225 1230
Val Glu Ser Leu Lys Asp Val Leu Ser Ser Ala Leu Gly Met Asp
1235 1240 1245
Glu Glu Gln Met Lys Thr Arg Lys Lys Ala Gln Arg Pro Lys Leu
1250 1255 1260
Glu Glu Val Leu Leu Lys Glu Glu Val Lys Glu Glu Pro Lys Lys
1265 1270 1275
Lys Ile Thr Lys Lys Lys Val Arg Phe Asp Ile Lys Asp Lys Glu
1280 1285 1290
Pro Lys Asp Glu Ile Val Glu Val Glu Met Lys Asp Glu Asp Ile
1295 1300 1305
Asp Glu Asp Ile Glu Glu Asp Val Glu Glu Asp Ile Glu Glu Asp
1310 1315 1320
Lys Val Glu Asp Ile Asp Glu Asp Ile Asp Glu Asp Ile Asp Glu
1325 1330 1335
Asp Ile Gly Glu Asp Lys Asp Glu Val Ile Asp Leu Ile Val Gln
1340 1345 1350
Lys Glu Lys Arg Ile Glu Lys Val Lys Glu Lys Lys Lys Lys Leu
1355 1360 1365
Glu Lys Lys Val Glu Glu Gly Val Ser Gly Leu Lys Lys His Val
1370 1375 1380
Asp Glu Val Met Lys Tyr Val Gln Lys Ile Asp Lys Glu Val Asp
1385 1390 1395
Lys Glu Val Ser Lys Ala Leu Glu Ser Lys Asn Asp Val Thr Asn
1400 1405 1410
Val Leu Lys Gln Asn Gln Asp Phe Phe Ser Lys Val Lys Asn Phe
1415 1420 1425
Val Lys Lys Tyr Lys Val Phe Ala Ala Pro Phe Ile Ser Ala Val
1430 1435 1440
Ala Ala Phe Ala Ser Tyr Val Val Gly Phe Phe Thr Phe Ser Leu
1445 1450 1455
Phe Ser Ser Cys Val Thr Ile Ala Ser Ser Thr Tyr Leu Leu Ser
1460 1465 1470
Lys Val Asp Lys Thr Ile Asn Lys Asn Lys Glu Arg Pro Phe Tyr
1475 1480 1485
Ser Phe Val Phe Asp Ile Phe Lys Asn Leu Lys His Tyr Leu Gln
1490 1495 1500
Gln Met Lys Glu Lys Phe Ser Lys Glu Lys Asn Asn Asn Val Ile
1505 1510 1515
Glu Val Thr Asn Lys Ala Glu Lys Lys Gly Asn Val Gln Val Thr
1520 1525 1530
Asn Lys Thr Glu Lys Thr Thr Lys Val Asp Lys Asn Asn Lys Val
1535 1540 1545
Pro Lys Lys Ser Arg Thr Gln Lys Ser Lys
1550 1555
<210> 77
<211> 150
<212> PRT
<213> 恶性疟原虫
<400> 77
Ser Asp Glu Leu Phe Asn Glu Leu Leu Asn Ser Val Asp Val Asn Gly
1 5 10 15
Glu Val Lys Glu Asn Ile Leu Glu Glu Ser Gln Val Asn Asp Asp Ile
20 25 30
Phe Asn Ser Leu Val Lys Ser Val Gln Gln Glu Gln Gln His Asn Val
35 40 45
Glu Glu Lys Val Glu Glu Ser Val Glu Glu Asn Asp Glu Glu Ser Val
50 55 60
Glu Glu Asn Val Glu Glu Asn Val Glu Glu Asn Asp Asp Glu Ser Val
65 70 75 80
Ala Ser Ser Val Glu Glu Ser Ile Ala Ser Ser Val Asp Glu Ser Ile
85 90 95
Asp Ser Ser Ile Glu Glu Asn Val Ala Pro Thr Val Glu Glu Ile Val
100 105 110
Ala Pro Thr Val Glu Glu Ile Val Ala Pro Ser Val Val Glu Ser Val
115 120 125
Ala Pro Ser Val Glu Glu Ser Val Glu Glu Asn Val Glu Glu Ser Val
130 135 140
Ala Glu Asn Val Glu Glu
145 150
<210> 78
<211> 397
<212> PRT
<213> 恶性疟原虫
<400> 78
Met Met Arg Lys Leu Ala Ile Leu Ser Val Ser Ser Phe Leu Phe Val
1 5 10 15
Glu Ala Leu Phe Gln Glu Tyr Gln Cys Tyr Gly Ser Ser Ser Asn Thr
20 25 30
Arg Val Leu Asn Glu Leu Asn Tyr Asp Asn Ala Gly Thr Asn Leu Tyr
35 40 45
Asn Glu Leu Glu Met Asn Tyr Tyr Gly Lys Gln Glu Asn Trp Tyr Ser
50 55 60
Leu Lys Lys Asn Ser Arg Ser Leu Gly Glu Asn Asp Asp Gly Asn Asn
65 70 75 80
Glu Asp Asn Glu Lys Leu Arg Lys Pro Lys His Lys Lys Leu Lys Gln
85 90 95
Pro Ala Asp Gly Asn Pro Asp Pro Asn Ala Asn Pro Asn Val Asp Pro
100 105 110
Asn Ala Asn Pro Asn Val Asp Pro Asn Ala Asn Pro Asn Val Asp Pro
115 120 125
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
130 135 140
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
145 150 155 160
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
165 170 175
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
180 185 190
Asn Ala Asn Pro Asn Val Asp Pro Asn Ala Asn Pro Asn Ala Asn Pro
195 200 205
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
210 215 220
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
225 230 235 240
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
245 250 255
Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro Asn Ala Asn Pro
260 265 270
Asn Lys Asn Asn Gln Gly Asn Gly Gln Gly His Asn Met Pro Asn Asp
275 280 285
Pro Asn Arg Asn Val Asp Glu Asn Ala Asn Ala Asn Ser Ala Val Lys
290 295 300
Asn Asn Asn Asn Glu Glu Pro Ser Asp Lys His Ile Lys Glu Tyr Leu
305 310 315 320
Asn Lys Ile Gln Asn Ser Leu Ser Thr Glu Trp Ser Pro Cys Ser Val
325 330 335
Thr Cys Gly Asn Gly Ile Gln Val Arg Ile Lys Pro Gly Ser Ala Asn
340 345 350
Lys Pro Lys Asp Glu Leu Asp Tyr Ala Asn Asp Ile Glu Lys Lys Ile
355 360 365
Cys Lys Met Glu Lys Cys Ser Ser Val Phe Asn Val Val Asn Ser Ser
370 375 380
Ile Gly Leu Ile Met Val Leu Ser Phe Leu Phe Leu Asn
385 390 395
<210> 79
<211> 574
<212> PRT
<213> 恶性疟原虫
<400> 79
Met Asn His Leu Gly Asn Val Lys Tyr Leu Val Ile Val Phe Leu Ile
1 5 10 15
Phe Phe Asp Leu Phe Leu Val Asn Gly Arg Asp Val Gln Asn Asn Ile
20 25 30
Val Asp Glu Ile Lys Tyr Arg Glu Glu Val Cys Asn Asp Glu Val Asp
35 40 45
Leu Tyr Leu Leu Met Asp Cys Ser Gly Ser Ile Arg Arg His Asn Trp
50 55 60
Val Asn His Ala Val Pro Leu Ala Met Lys Leu Ile Gln Gln Leu Asn
65 70 75 80
Leu Asn Asp Asn Ala Ile His Leu Tyr Ala Ser Val Phe Ser Asn Asn
85 90 95
Ala Arg Glu Ile Ile Arg Leu His Ser Asp Ala Ser Lys Asn Lys Glu
100 105 110
Lys Ala Leu Ile Ile Ile Lys Ser Leu Leu Ser Thr Asn Leu Pro Tyr
115 120 125
Gly Lys Thr Asn Leu Thr Asp Ala Leu Leu Gln Val Arg Lys His Leu
130 135 140
Asn Asp Arg Ile Asn Arg Glu Asn Ala Asn Gln Leu Val Val Ile Leu
145 150 155 160
Thr Asp Gly Ile Pro Asp Ser Ile Gln Asp Ser Leu Lys Glu Ser Arg
165 170 175
Lys Leu Ser Asp Arg Gly Val Lys Ile Ala Val Phe Gly Ile Gly Gln
180 185 190
Gly Ile Asn Val Ala Phe Asn Arg Phe Leu Val Gly Cys His Pro Ser
195 200 205
Asp Gly Lys Cys Asn Leu Tyr Ala Asp Ser Ala Trp Glu Asn Val Lys
210 215 220
Asn Val Ile Gly Pro Phe Met Lys Ala Val Cys Val Glu Val Glu Lys
225 230 235 240
Thr Ala Ser Cys Gly Val Trp Asp Glu Trp Ser Pro Cys Ser Val Thr
245 250 255
Cys Gly Lys Gly Thr Arg Ser Arg Lys Arg Glu Ile Leu His Glu Gly
260 265 270
Cys Thr Ser Glu Leu Gln Glu Gln Cys Glu Glu Glu Arg Cys Leu Pro
275 280 285
Lys Arg Glu Pro Leu Asp Val Pro Asp Glu Pro Glu Asp Asp Gln Pro
290 295 300
Arg Pro Arg Gly Asp Asn Phe Ala Val Glu Lys Pro Asn Glu Asn Ile
305 310 315 320
Ile Asp Asn Asn Pro Gln Glu Pro Ser Pro Asn Pro Glu Glu Gly Lys
325 330 335
Gly Glu Asn Pro Asn Gly Phe Asp Leu Asp Glu Asn Pro Glu Asn Pro
340 345 350
Pro Asn Pro Pro Asn Pro Pro Asn Pro Pro Asn Pro Pro Asn Pro Pro
355 360 365
Asn Pro Asp Ile Pro Glu Gln Glu Pro Asn Ile Pro Glu Asp Ser Glu
370 375 380
Lys Glu Val Pro Ser Asp Val Pro Lys Asn Pro Glu Asp Asp Arg Glu
385 390 395 400
Glu Asn Phe Asp Ile Pro Lys Lys Pro Glu Asn Lys His Asp Asn Gln
405 410 415
Asn Asn Leu Pro Asn Asp Lys Ser Asp Arg Tyr Ile Pro Tyr Ser Pro
420 425 430
Leu Ser Pro Lys Val Leu Asp Asn Glu Arg Lys Gln Ser Asp Pro Gln
435 440 445
Ser Gln Asp Asn Asn Gly Asn Arg His Val Pro Asn Ser Glu Asp Arg
450 455 460
Glu Thr Arg Pro His Gly Arg Asn Asn Glu Asn Arg Ser Tyr Asn Arg
465 470 475 480
Lys His Asn Asn Thr Pro Lys His Pro Glu Arg Glu Glu His Glu Lys
485 490 495
Pro Asp Asn Asn Lys Lys Lys Ala Gly Ser Asp Asn Lys Tyr Lys Ile
500 505 510
Ala Gly Gly Ile Ala Gly Gly Leu Ala Leu Leu Ala Cys Ala Gly Leu
515 520 525
Ala Tyr Lys Phe Val Val Pro Gly Ala Ala Thr Pro Tyr Ala Gly Glu
530 535 540
Pro Ala Pro Phe Asp Glu Thr Leu Gly Glu Glu Asp Lys Asp Leu Asp
545 550 555 560
Glu Pro Glu Gln Phe Arg Leu Pro Glu Glu Asn Glu Trp Asn
565 570
<210> 80
<211> 272
<212> PRT
<213> 恶性疟原虫
<400> 80
Met Trp Ile Val Lys Phe Leu Ile Val Val His Phe Phe Ile Ile Cys
1 5 10 15
Thr Ile Asn Phe Asp Lys Leu Tyr Ile Ser Tyr Ser Tyr Asn Ile Val
20 25 30
Pro Glu Asn Gly Arg Met Leu Asn Met Arg Ile Leu Gly Glu Glu Lys
35 40 45
Pro Asn Val Asp Gly Val Ser Thr Ser Asn Thr Pro Gly Gly Asn Glu
50 55 60
Ser Ser Ser Ala Ser Pro Asn Leu Ser Asp Ala Ala Glu Lys Lys Asp
65 70 75 80
Glu Lys Glu Ala Ser Glu Gln Gly Glu Glu Ser His Lys Lys Glu Asn
85 90 95
Ser Gln Glu Ser Ala Asn Gly Lys Asp Asp Val Lys Glu Glu Lys Lys
100 105 110
Thr Asn Glu Lys Lys Asp Asp Gly Lys Thr Asp Lys Val Gln Glu Lys
115 120 125
Val Leu Glu Lys Ser Pro Lys Glu Ser Gln Met Val Asp Asp Lys Lys
130 135 140
Lys Thr Glu Ala Ile Pro Lys Lys Val Val Gln Pro Ser Ser Ser Asn
145 150 155 160
Ser Gly Gly His Val Gly Glu Glu Glu Asp His Asn Glu Gly Glu Gly
165 170 175
Glu His Glu Glu Glu Glu Glu His Glu Glu Asp Asp Asp Asp Glu Asp
180 185 190
Asp Asp Thr Tyr Asn Lys Asp Asp Leu Glu Asp Glu Asp Leu Cys Lys
195 200 205
His Asn Asn Gly Gly Cys Gly Asp Asp Lys Leu Cys Glu Tyr Val Gly
210 215 220
Asn Arg Arg Val Lys Cys Lys Cys Lys Glu Gly Tyr Lys Leu Glu Gly
225 230 235 240
Ile Glu Cys Val Glu Leu Leu Ser Leu Ala Ser Ser Ser Leu Asn Leu
245 250 255
Ile Phe Asn Ser Phe Ile Thr Ile Phe Val Val Ile Leu Leu Ile Asn
260 265 270
<210> 81
<211> 560
<212> PRT
<213> 恶性疟原虫
<400> 81
Met Ser Arg Lys Leu Phe Ala Ser Ile Leu Ile Gly Ala Leu Leu Gly
1 5 10 15
Ile Gly Ala Pro Pro Ser Ala His Ala Gly Ala Asp Asp Val Val Asp
20 25 30
Ser Ser Lys Ser Phe Val Met Glu Asn Phe Ser Ser Tyr His Gly Thr
35 40 45
Lys Pro Gly Tyr Val Asp Ser Ile Gln Lys Gly Ile Gln Lys Pro Lys
50 55 60
Ser Gly Thr Gln Gly Asn Tyr Asp Asp Asp Trp Lys Gly Phe Tyr Ser
65 70 75 80
Thr Asp Asn Lys Tyr Asp Ala Ala Gly Tyr Ser Val Asp Asn Glu Asn
85 90 95
Pro Leu Ser Gly Lys Ala Gly Gly Val Val Lys Val Thr Tyr Pro Gly
100 105 110
Leu Thr Lys Val Leu Ala Leu Lys Val Asp Asn Ala Glu Thr Ile Lys
115 120 125
Lys Glu Leu Gly Leu Ser Leu Thr Glu Pro Leu Met Glu Gln Val Gly
130 135 140
Thr Glu Glu Phe Ile Lys Arg Phe Gly Asp Gly Ala Ser Arg Val Val
145 150 155 160
Leu Ser Leu Pro Phe Ala Glu Gly Ser Ser Ser Val Glu Tyr Ile Asn
165 170 175
Asn Trp Glu Gln Ala Lys Ala Leu Ser Val Glu Leu Glu Ile Asn Phe
180 185 190
Glu Thr Arg Gly Lys Arg Gly Gln Asp Ala Met Tyr Glu Tyr Met Ala
195 200 205
Gln Ala Cys Ala Gly Asn Arg Val Arg Arg Ser Val Gly Ser Ser Leu
210 215 220
Ser Cys Ile Asn Leu Asp Trp Asp Val Ile Arg Asp Lys Thr Lys Thr
225 230 235 240
Lys Ile Glu Ser Leu Lys Glu His Gly Pro Ile Lys Asn Lys Met Ser
245 250 255
Glu Ser Pro Asn Lys Thr Val Ser Glu Glu Lys Ala Lys Gln Tyr Leu
260 265 270
Glu Glu Phe His Gln Thr Ala Leu Glu His Pro Glu Leu Ser Glu Leu
275 280 285
Lys Thr Val Thr Gly Thr Asn Pro Val Phe Ala Gly Ala Asn Tyr Ala
290 295 300
Ala Trp Ala Val Asn Val Ala Gln Val Ile Asp Ser Glu Thr Ala Asp
305 310 315 320
Asn Leu Glu Lys Thr Thr Ala Ala Leu Ser Ile Leu Pro Gly Ile Gly
325 330 335
Ser Val Met Gly Ile Ala Asp Gly Ala Val His His Asn Thr Glu Glu
340 345 350
Ile Val Ala Gln Ser Ile Ala Leu Ser Ser Leu Met Val Ala Gln Ala
355 360 365
Ile Pro Leu Val Gly Glu Leu Val Asp Ile Gly Phe Ala Ala Tyr Asn
370 375 380
Phe Val Glu Ser Ile Ile Asn Leu Phe Gln Val Val His Asn Ser Tyr
385 390 395 400
Asn Arg Pro Ala Tyr Ser Pro Gly His Lys Thr Gln Pro Phe Leu His
405 410 415
Asp Gly Tyr Ala Val Ser Trp Asn Thr Val Glu Asp Ser Ile Ile Arg
420 425 430
Thr Gly Phe Gln Gly Glu Ser Gly His Asp Ile Lys Ile Thr Ala Glu
435 440 445
Asn Thr Pro Leu Pro Ile Ala Gly Val Leu Leu Pro Thr Ile Pro Gly
450 455 460
Lys Leu Asp Val Asn Lys Ser Lys Thr His Ile Ser Val Asn Gly Arg
465 470 475 480
Lys Ile Arg Met Arg Cys Arg Ala Ile Asp Gly Asp Val Thr Phe Cys
485 490 495
Arg Pro Lys Ser Pro Val Tyr Val Gly Asn Gly Val His Ala Asn Leu
500 505 510
His Val Ala Phe His Arg Ser Ser Ser Glu Lys Ile His Ser Asn Glu
515 520 525
Ile Ser Ser Asp Ser Ile Gly Val Leu Gly Tyr Gln Lys Thr Val Asp
530 535 540
His Thr Lys Val Asn Ser Lys Leu Ser Leu Phe Phe Glu Ile Lys Ser
545 550 555 560
<210> 82
<211> 535
<212> PRT
<213> 恶性疟原虫
<400> 82
Gly Ala Asp Asp Val Val Asp Ser Ser Lys Ser Phe Val Met Glu Asn
1 5 10 15
Phe Ser Ser Tyr His Gly Thr Lys Pro Gly Tyr Val Asp Ser Ile Gln
20 25 30
Lys Gly Ile Gln Lys Pro Lys Ser Gly Thr Gln Gly Asn Tyr Asp Asp
35 40 45
Asp Trp Lys Glu Phe Tyr Ser Thr Asp Asn Lys Tyr Asp Ala Ala Gly
50 55 60
Tyr Ser Val Asp Asn Glu Asn Pro Leu Ser Gly Lys Ala Gly Gly Val
65 70 75 80
Val Lys Val Thr Tyr Pro Gly Leu Thr Lys Val Leu Ala Leu Lys Val
85 90 95
Asp Asn Ala Glu Thr Ile Lys Lys Glu Leu Gly Leu Ser Leu Thr Glu
100 105 110
Pro Leu Met Glu Gln Val Gly Thr Glu Glu Phe Ile Lys Arg Phe Gly
115 120 125
Asp Gly Ala Ser Arg Val Val Leu Ser Leu Pro Phe Ala Glu Gly Ser
130 135 140
Ser Ser Val Glu Tyr Ile Asn Asn Trp Glu Gln Ala Lys Ala Leu Ser
145 150 155 160
Val Glu Leu Glu Ile Asn Phe Glu Thr Arg Gly Lys Arg Gly Gln Asp
165 170 175
Ala Met Tyr Glu Tyr Met Ala Gln Ala Cys Ala Gly Asn Arg Val Arg
180 185 190
Arg Ser Val Gly Ser Ser Leu Ser Cys Ile Asn Leu Asp Trp Asp Val
195 200 205
Ile Arg Asp Lys Thr Lys Thr Lys Ile Glu Ser Leu Lys Glu His Gly
210 215 220
Pro Ile Lys Asn Lys Met Ser Glu Ser Pro Asn Lys Thr Val Ser Glu
225 230 235 240
Glu Lys Ala Lys Gln Tyr Leu Glu Glu Phe His Gln Thr Ala Leu Glu
245 250 255
His Pro Glu Leu Ser Glu Leu Lys Thr Val Thr Gly Thr Asn Pro Val
260 265 270
Phe Ala Gly Ala Asn Tyr Ala Ala Trp Ala Val Asn Val Ala Gln Val
275 280 285
Ile Asp Ser Glu Thr Ala Asp Asn Leu Glu Lys Thr Thr Ala Ala Leu
290 295 300
Ser Ile Leu Pro Gly Ile Gly Ser Val Met Gly Ile Ala Asp Gly Ala
305 310 315 320
Val His His Asn Thr Glu Glu Ile Val Ala Gln Ser Ile Ala Leu Ser
325 330 335
Ser Leu Met Val Ala Gln Ala Ile Pro Leu Val Gly Glu Leu Val Asp
340 345 350
Ile Gly Phe Ala Ala Tyr Asn Phe Val Glu Ser Ile Ile Asn Leu Phe
355 360 365
Gln Val Val His Asn Ser Tyr Asn Arg Pro Ala Tyr Ser Pro Gly His
370 375 380
Lys Thr Gln Pro Phe Leu His Asp Gly Tyr Ala Val Ser Trp Asn Thr
385 390 395 400
Val Glu Asp Ser Ile Ile Arg Thr Gly Phe Gln Gly Glu Ser Gly His
405 410 415
Asp Ile Lys Ile Thr Ala Glu Asn Thr Pro Leu Pro Ile Ala Gly Val
420 425 430
Leu Leu Pro Thr Ile Pro Gly Lys Leu Asp Val Asn Lys Ser Lys Thr
435 440 445
His Ile Ser Val Asn Gly Arg Lys Ile Arg Met Arg Cys Arg Ala Ile
450 455 460
Asp Gly Asp Val Thr Phe Cys Arg Pro Lys Ser Pro Val Tyr Val Gly
465 470 475 480
Asn Gly Val His Ala Asn Leu His Val Ala Phe His Arg Ser Ser Ser
485 490 495
Glu Lys Ile His Ser Asn Glu Ile Ser Ser Asp Ser Ile Gly Val Leu
500 505 510
Gly Tyr Gln Lys Thr Val Asp His Thr Lys Val Asn Ser Lys Leu Ser
515 520 525
Leu Phe Phe Glu Ile Lys Ser
530 535
<210> 83
<211> 1315
<212> PRT
<213> 恶性疟原虫
<400> 83
Met Pro Ile Thr Ile Asn Asn Phe Arg Tyr Ser Asp Pro Val Asn Asn
1 5 10 15
Asp Thr Ile Ile Met Met Glu Pro Pro Tyr Cys Lys Gly Leu Asp Ile
20 25 30
Tyr Tyr Lys Ala Phe Lys Ile Thr Asp Arg Ile Trp Ile Val Pro Glu
35 40 45
Arg Tyr Glu Phe Gly Thr Lys Pro Glu Asp Phe Asn Pro Pro Ser Ser
50 55 60
Leu Ile Glu Gly Ala Ser Glu Tyr Tyr Asp Pro Asn Tyr Leu Arg Thr
65 70 75 80
Asp Ser Asp Lys Asp Arg Phe Leu Gln Thr Met Val Lys Leu Phe Asn
85 90 95
Arg Ile Lys Asn Asn Val Ala Gly Glu Ala Leu Leu Asp Lys Ile Ile
100 105 110
Asn Ala Ile Pro Tyr Leu Gly Asn Ser Tyr Ser Leu Leu Asp Lys Phe
115 120 125
Asp Thr Asn Ser Asn Ser Val Ser Phe Asn Leu Leu Glu Gln Asp Pro
130 135 140
Ser Gly Ala Thr Thr Lys Ser Ala Met Leu Thr Asn Leu Ile Ile Phe
145 150 155 160
Gly Pro Gly Pro Val Leu Asn Lys Asn Glu Val Arg Gly Ile Val Leu
165 170 175
Arg Val Asp Asn Lys Asn Tyr Phe Pro Cys Arg Asp Gly Phe Gly Ser
180 185 190
Ile Met Gln Met Ala Phe Cys Pro Glu Tyr Val Pro Thr Phe Asp Asn
195 200 205
Val Ile Glu Asn Ile Thr Ser Leu Thr Ile Gly Lys Ser Lys Tyr Phe
210 215 220
Gln Asp Pro Ala Leu Leu Leu Met His Glu Leu Ile His Val Leu His
225 230 235 240
Gly Leu Tyr Gly Met Gln Val Ser Ser His Glu Ile Ile Pro Ser Lys
245 250 255
Gln Glu Ile Tyr Met Gln His Thr Tyr Pro Ile Ser Ala Glu Glu Leu
260 265 270
Phe Thr Phe Gly Gly Gln Asp Ala Asn Leu Ile Ser Ile Asp Ile Lys
275 280 285
Asn Asp Leu Tyr Glu Lys Thr Leu Asn Asp Tyr Lys Ala Ile Ala Asn
290 295 300
Lys Leu Ser Gln Val Thr Ser Cys Asn Asp Pro Asn Ile Asp Ile Asp
305 310 315 320
Ser Tyr Lys Gln Ile Tyr Gln Gln Lys Tyr Gln Phe Asp Lys Asp Ser
325 330 335
Asn Gly Gln Tyr Ile Val Asn Glu Asp Lys Phe Gln Ile Leu Tyr Asn
340 345 350
Ser Ile Met Tyr Gly Phe Thr Glu Ile Glu Leu Gly Lys Lys Phe Asn
355 360 365
Ile Lys Thr Arg Leu Ser Tyr Phe Ser Met Asn His Asp Pro Val Lys
370 375 380
Ile Pro Asn Leu Leu Asp Asp Thr Ile Tyr Asn Asp Thr Glu Gly Phe
385 390 395 400
Asn Ile Glu Ser Lys Asp Leu Lys Ser Glu Tyr Lys Gly Gln Asn Met
405 410 415
Arg Val Asn Thr Asn Ala Phe Arg Asn Val Asp Gly Ser Gly Leu Val
420 425 430
Ser Lys Leu Ile Gly Leu Cys Lys Lys Ile Ile Pro Pro Thr Asn Ile
435 440 445
Arg Glu Asn Leu Tyr Asn Arg Thr Ala Ser Leu Thr Asp Leu Gly Gly
450 455 460
Glu Leu Cys Ile Lys Ile Lys Asn Glu Asp Leu Thr Phe Ile Ala Glu
465 470 475 480
Lys Asn Ser Phe Ser Glu Glu Pro Phe Gln Asp Glu Ile Val Ser Tyr
485 490 495
Asn Thr Lys Asn Lys Pro Leu Asn Phe Asn Tyr Ser Leu Asp Lys Ile
500 505 510
Ile Val Asp Tyr Asn Leu Gln Ser Lys Ile Thr Leu Pro Asn Asp Arg
515 520 525
Thr Thr Pro Val Thr Lys Gly Ile Pro Tyr Ala Pro Glu Tyr Lys Ser
530 535 540
Asn Ala Ala Ser Thr Ile Glu Ile His Asn Ile Asp Asp Asn Thr Ile
545 550 555 560
Tyr Gln Tyr Leu Tyr Ala Gln Lys Ser Pro Thr Thr Leu Gln Arg Ile
565 570 575
Thr Met Thr Asn Ser Val Asp Asp Ala Leu Ile Asn Ser Thr Lys Ile
580 585 590
Tyr Ser Tyr Phe Pro Ser Val Ile Ser Lys Val Asn Gln Gly Ala Gln
595 600 605
Gly Ile Leu Phe Leu Gln Trp Val Arg Asp Ile Ile Asp Asp Phe Thr
610 615 620
Asn Glu Ser Ser Gln Lys Thr Thr Ile Asp Lys Ile Ser Asp Val Ser
625 630 635 640
Thr Ile Val Pro Tyr Ile Gly Pro Ala Leu Asn Ile Val Lys Gln Gly
645 650 655
Tyr Glu Gly Asn Phe Ile Gly Ala Leu Glu Thr Thr Gly Val Val Leu
660 665 670
Leu Leu Glu Tyr Ile Pro Glu Ile Thr Leu Pro Val Ile Ala Ala Leu
675 680 685
Ser Ile Ala Glu Ser Ser Thr Gln Lys Glu Lys Ile Ile Lys Thr Ile
690 695 700
Asp Asn Phe Leu Glu Lys Arg Tyr Glu Lys Trp Ile Glu Val Tyr Lys
705 710 715 720
Leu Val Lys Ala Lys Trp Leu Gly Thr Val Asn Thr Gln Phe Gln Lys
725 730 735
Arg Ser Tyr Gln Met Tyr Arg Ser Leu Glu Tyr Gln Val Asp Ala Ile
740 745 750
Lys Lys Ile Ile Asp Tyr Glu Tyr Lys Ile Tyr Ser Gly Pro Asp Lys
755 760 765
Glu Gln Ile Ala Asp Glu Ile Asn Asn Leu Lys Asn Lys Leu Glu Glu
770 775 780
Lys Ala Asn Lys Ala Met Ile Asn Ile Asn Ile Phe Met Arg Glu Ser
785 790 795 800
Ser Arg Ser Phe Leu Val Asn Gln Met Ile Asn Glu Ala Lys Lys Gln
805 810 815
Leu Leu Glu Phe Asp Thr Gln Ser Lys Asn Ile Leu Met Gln Tyr Ile
820 825 830
Lys Ala Asn Ser Lys Phe Ile Gly Ile Thr Glu Leu Lys Lys Leu Glu
835 840 845
Ser Lys Ile Asn Lys Val Phe Ser Thr Pro Ile Pro Phe Ser Tyr Ser
850 855 860
Lys Asn Leu Asp Cys Trp Val Asp Asn Glu Glu Asp Ile Asp Val Ile
865 870 875 880
Leu Lys Lys Ser Thr Ile Leu Asn Leu Asp Ile Asn Asn Asp Ile Ile
885 890 895
Ser Asp Ile Ser Gly Phe Asn Ser Ser Val Ile Thr Tyr Pro Asp Ala
900 905 910
Gln Leu Val Pro Gly Ile Asn Gly Lys Ala Ile His Leu Val Asn Asn
915 920 925
Glu Ser Ser Glu Val Ile Val His Lys Ala Met Asp Ile Glu Tyr Asn
930 935 940
Asp Met Phe Asn Asn Phe Thr Val Ser Phe Trp Leu Arg Val Pro Lys
945 950 955 960
Val Ser Ala Ser His Leu Glu Gln Tyr Gly Thr Asn Glu Tyr Ser Ile
965 970 975
Ile Ser Ser Met Lys Lys His Ser Leu Ser Ile Gly Ser Gly Trp Ser
980 985 990
Val Ser Leu Lys Gly Asn Asn Leu Ile Trp Thr Leu Lys Asp Ser Ala
995 1000 1005
Gly Glu Val Arg Gln Ile Thr Phe Arg Asp Leu Pro Asp Lys Phe
1010 1015 1020
Asn Ala Tyr Leu Ala Asn Lys Trp Val Phe Ile Thr Ile Thr Asn
1025 1030 1035
Asp Arg Leu Ser Ser Ala Asn Leu Tyr Ile Asn Gly Val Leu Met
1040 1045 1050
Gly Ser Ala Glu Ile Thr Gly Leu Gly Ala Ile Arg Glu Asp Asn
1055 1060 1065
Asn Ile Thr Leu Lys Leu Asp Arg Cys Asn Asn Asn Asn Gln Tyr
1070 1075 1080
Val Ser Ile Asp Lys Phe Arg Ile Phe Cys Lys Ala Leu Asn Pro
1085 1090 1095
Lys Glu Ile Glu Lys Leu Tyr Thr Ser Tyr Leu Ser Ile Thr Phe
1100 1105 1110
Leu Arg Asp Phe Trp Gly Asn Pro Leu Arg Tyr Asp Thr Glu Tyr
1115 1120 1125
Tyr Leu Ile Pro Val Ala Ser Ser Ser Lys Asp Val Gln Leu Lys
1130 1135 1140
Asn Ile Thr Asp Tyr Met Tyr Leu Thr Asn Ala Pro Ser Tyr Thr
1145 1150 1155
Asn Gly Lys Leu Asn Ile Tyr Tyr Arg Arg Leu Tyr Asn Gly Leu
1160 1165 1170
Lys Phe Ile Ile Lys Arg Tyr Thr Pro Asn Asn Glu Ile Asp Ser
1175 1180 1185
Phe Val Lys Ser Gly Asp Phe Ile Lys Leu Tyr Val Ser Tyr Asn
1190 1195 1200
Asn Asn Glu His Ile Val Gly Tyr Pro Lys Asp Gly Asn Ala Phe
1205 1210 1215
Asn Asn Leu Asp Arg Ile Leu Arg Val Gly Tyr Asn Ala Pro Gly
1220 1225 1230
Ile Pro Leu Tyr Lys Lys Met Glu Ala Val Lys Leu Arg Asp Leu
1235 1240 1245
Lys Thr Tyr Ser Val Gln Leu Lys Leu Tyr Asp Asp Lys Asn Ala
1250 1255 1260
Ser Leu Gly Leu Val Gly Thr His Asn Gly Gln Ile Gly Asn Asp
1265 1270 1275
Pro Asn Arg Asp Ile Leu Ile Ala Ser Asn Trp Tyr Phe Asn His
1280 1285 1290
Leu Lys Asp Lys Ile Leu Gly Cys Asp Trp Tyr Phe Val Pro Thr
1295 1300 1305
Asp Glu Gly Trp Thr Asn Asp
1310 1315
<210> 84
<211> 364
<212> PRT
<213> 恶性疟原虫
<400> 84
Met Lys Leu Lys Thr Leu Ala Leu Ser Leu Leu Ala Ala Gly Val Leu
1 5 10 15
Ala Gly Cys Ser Ser His Ser Ser Asn Met Ala Asn Thr Gln Met Lys
20 25 30
Ser Asp Lys Ile Ile Ile Ala His Arg Gly Ala Ser Gly Tyr Leu Pro
35 40 45
Glu His Thr Leu Glu Ser Lys Ala Leu Ala Phe Ala Gln Gln Ala Asp
50 55 60
Tyr Leu Glu Gln Asp Leu Ala Met Thr Lys Asp Gly Arg Leu Val Val
65 70 75 80
Ile His Asp His Phe Leu Asp Gly Leu Thr Asp Val Ala Lys Lys Phe
85 90 95
Pro His Arg His Arg Lys Asp Gly Arg Tyr Tyr Val Ile Asp Phe Thr
100 105 110
Leu Lys Glu Ile Gln Ser Leu Glu Met Thr Glu Asn Phe Glu Thr Lys
115 120 125
Asp Gly Lys Gln Ala Gln Val Tyr Pro Asn Arg Phe Pro Leu Trp Lys
130 135 140
Ser His Phe Arg Ile His Thr Phe Glu Asp Glu Ile Glu Phe Ile Gln
145 150 155 160
Gly Leu Glu Lys Ser Thr Gly Lys Lys Val Gly Ile Tyr Pro Glu Ile
165 170 175
Lys Ala Pro Trp Phe His His Gln Asn Gly Lys Asp Ile Ala Ala Glu
180 185 190
Thr Leu Lys Val Leu Lys Lys Tyr Gly Tyr Asp Lys Lys Thr Asp Met
195 200 205
Val Tyr Leu Gln Thr Phe Asp Phe Asn Glu Leu Lys Arg Ile Lys Thr
210 215 220
Glu Leu Leu Pro Gln Met Gly Met Asp Leu Lys Leu Val Gln Leu Ile
225 230 235 240
Ala Tyr Thr Asp Trp Lys Glu Thr Gln Glu Lys Asp Pro Lys Gly Tyr
245 250 255
Trp Val Asn Tyr Asn Tyr Asp Trp Met Phe Lys Pro Gly Ala Met Ala
260 265 270
Glu Val Val Lys Tyr Ala Asp Gly Val Gly Pro Gly Trp Tyr Met Leu
275 280 285
Val Asn Lys Glu Glu Ser Lys Pro Asp Asn Ile Val Tyr Thr Pro Leu
290 295 300
Val Lys Glu Leu Ala Gln Tyr Asn Val Glu Val His Pro Tyr Thr Val
305 310 315 320
Arg Lys Asp Ala Leu Pro Ala Phe Phe Thr Asp Val Asn Gln Met Tyr
325 330 335
Asp Ala Leu Leu Asn Lys Ser Gly Ala Thr Gly Val Phe Thr Asp Phe
340 345 350
Pro Asp Thr Gly Val Glu Phe Leu Lys Gly Ile Lys
355 360
<210> 85
<211> 757
<212> PRT
<213> 人工序列
<220>
<223> PP21生物融合蛋白
<400> 85
Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala
1 5 10 15
Ala Gln Pro Ala Met Ala Met Gly Lys Thr Lys Glu Tyr Ala Glu Lys
20 25 30
Ala Lys Asn Ala Tyr Glu Lys Ala Lys Asn Ala Tyr Gln Lys Ala Asn
35 40 45
Gln Ala Val Leu Lys Ala Lys Glu Ala Ser Ser Tyr Asp Tyr Ile Leu
50 55 60
Gly Trp Glu Phe Gly Gly Gly Val Pro Glu His Lys Lys Glu Glu Asn
65 70 75 80
Met Leu Ser His Leu Tyr Val Ser Ser Lys Asp Lys Glu Asn Ile Ser
85 90 95
Lys Glu Asn Asp Asp Val Leu Asp Glu Lys Glu Glu Glu Ala Glu Glu
100 105 110
Thr Glu Glu Glu Glu Leu Glu Gly Ala Asp Asp Val Val Asp Ser Ser
115 120 125
Lys Ser Phe Val Met Glu Asn Phe Ser Ser Tyr His Gly Thr Lys Pro
130 135 140
Gly Tyr Val Asp Ser Ile Gln Lys Gly Ile Gln Lys Pro Lys Ser Gly
145 150 155 160
Thr Gln Gly Asn Tyr Asp Asp Asp Trp Lys Glu Phe Tyr Ser Thr Asp
165 170 175
Asn Lys Tyr Asp Ala Ala Gly Tyr Ser Val Asp Asn Glu Asn Pro Leu
180 185 190
Ser Gly Lys Ala Gly Gly Val Val Lys Val Thr Tyr Pro Gly Leu Thr
195 200 205
Lys Val Leu Ala Leu Lys Val Asp Asn Ala Glu Thr Ile Lys Lys Glu
210 215 220
Leu Gly Leu Ser Leu Thr Glu Pro Leu Met Glu Gln Val Gly Thr Glu
225 230 235 240
Glu Phe Ile Lys Arg Phe Gly Asp Gly Ala Ser Arg Val Val Leu Ser
245 250 255
Leu Pro Phe Ala Glu Gly Ser Ser Ser Val Glu Tyr Ile Asn Asn Trp
260 265 270
Glu Gln Ala Lys Ala Leu Ser Val Glu Leu Glu Ile Asn Phe Glu Thr
275 280 285
Arg Gly Lys Arg Gly Gln Asp Ala Met Tyr Glu Tyr Met Ala Gln Ala
290 295 300
Cys Ala Gly Asn Arg Val Arg Arg Ser Val Gly Ser Ser Leu Ser Cys
305 310 315 320
Ile Asn Leu Asp Trp Asp Val Ile Arg Asp Lys Thr Lys Thr Lys Ile
325 330 335
Glu Ser Leu Lys Glu His Gly Pro Ile Lys Asn Lys Met Ser Glu Ser
340 345 350
Pro Asn Lys Thr Val Ser Glu Glu Lys Ala Lys Gln Tyr Leu Glu Glu
355 360 365
Phe His Gln Thr Ala Leu Glu His Pro Glu Leu Ser Glu Leu Lys Thr
370 375 380
Val Thr Gly Thr Asn Pro Val Phe Ala Gly Ala Asn Tyr Ala Ala Trp
385 390 395 400
Ala Val Asn Val Ala Gln Val Ile Asp Ser Glu Thr Ala Asp Asn Leu
405 410 415
Glu Lys Thr Thr Ala Ala Leu Ser Ile Leu Pro Gly Ile Gly Ser Val
420 425 430
Met Gly Ile Ala Asp Gly Ala Val His His Asn Thr Glu Glu Ile Val
435 440 445
Ala Gln Ser Ile Ala Leu Ser Ser Leu Met Val Ala Gln Ala Ile Pro
450 455 460
Leu Val Gly Glu Leu Val Asp Ile Gly Phe Ala Ala Tyr Asn Phe Val
465 470 475 480
Glu Ser Ile Ile Asn Leu Phe Gln Val Val His Asn Ser Tyr Asn Arg
485 490 495
Pro Ala Tyr Ser Pro Gly His Lys Thr Gln Pro Phe Leu His Asp Gly
500 505 510
Tyr Ala Val Ser Trp Asn Thr Val Glu Asp Ser Ile Ile Arg Thr Gly
515 520 525
Phe Gln Gly Glu Ser Gly His Asp Ile Lys Ile Thr Ala Glu Asn Thr
530 535 540
Pro Leu Pro Ile Ala Gly Val Leu Leu Pro Thr Ile Pro Gly Lys Leu
545 550 555 560
Asp Val Asn Lys Ser Lys Thr His Ile Ser Val Asn Gly Arg Lys Ile
565 570 575
Arg Met Arg Cys Arg Ala Ile Asp Gly Asp Val Thr Phe Cys Arg Pro
580 585 590
Lys Ser Pro Val Tyr Val Gly Asn Gly Val His Ala Asn Leu His Val
595 600 605
Ala Phe His Arg Ser Ser Ser Glu Lys Ile His Ser Asn Glu Ile Ser
610 615 620
Ser Asp Ser Ile Gly Val Leu Gly Tyr Gln Lys Thr Val Asp His Thr
625 630 635 640
Lys Val Asn Ser Lys Leu Ser Leu Phe Phe Glu Ile Lys Ser Lys Thr
645 650 655
Lys Glu Tyr Ala Glu Lys Ala Lys Asn Ala Tyr Glu Lys Ala Lys Asn
660 665 670
Ala Tyr Gln Lys Ala Asn Gln Ala Val Leu Lys Ala Lys Glu Ala Ser
675 680 685
Ser Tyr Asp Tyr Ile Leu Gly Trp Glu Phe Gly Gly Gly Val Pro Glu
690 695 700
His Lys Lys Glu Glu Asn Met Leu Ser His Leu Tyr Val Ser Ser Lys
705 710 715 720
Asp Lys Glu Asn Ile Ser Lys Glu Asn Asp Asp Val Leu Asp Glu Lys
725 730 735
Glu Glu Glu Ala Glu Glu Thr Glu Glu Glu Glu Leu Glu Leu Glu His
740 745 750
His His His His His
755
<210> 86
<211> 727
<212> PRT
<213> 人工序列
<220>
<223> PP22生物融合蛋白
<400> 86
Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala
1 5 10 15
Ala Gln Pro Ala Met Ala Met Gly Leu Asn Asn Asn Ile Leu Gly Trp
20 25 30
Glu Phe Gly Gly Gly Ala Pro Gln Asn Gly Ala Ala Glu Asp Lys Lys
35 40 45
Thr Glu Tyr Leu Leu Glu Gln Ile Lys Ile Pro Ser Trp Asp Arg Asn
50 55 60
Asn Ile Pro Asp Glu Asn Glu Gln Val Ile Glu Asp Pro Gln Glu Asp
65 70 75 80
Asn Lys Asp Glu Asp Glu Asp Glu Glu Thr Glu Thr Glu Asn Leu Glu
85 90 95
Thr Glu Asp Asp Asn Asn Glu Glu Gly Ala Asp Asp Val Val Asp Ser
100 105 110
Ser Lys Ser Phe Val Met Glu Asn Phe Ser Ser Tyr His Gly Thr Lys
115 120 125
Pro Gly Tyr Val Asp Ser Ile Gln Lys Gly Ile Gln Lys Pro Lys Ser
130 135 140
Gly Thr Gln Gly Asn Tyr Asp Asp Asp Trp Lys Glu Phe Tyr Ser Thr
145 150 155 160
Asp Asn Lys Tyr Asp Ala Ala Gly Tyr Ser Val Asp Asn Glu Asn Pro
165 170 175
Leu Ser Gly Lys Ala Gly Gly Val Val Lys Val Thr Tyr Pro Gly Leu
180 185 190
Thr Lys Val Leu Ala Leu Lys Val Asp Asn Ala Glu Thr Ile Lys Lys
195 200 205
Glu Leu Gly Leu Ser Leu Thr Glu Pro Leu Met Glu Gln Val Gly Thr
210 215 220
Glu Glu Phe Ile Lys Arg Phe Gly Asp Gly Ala Ser Arg Val Val Leu
225 230 235 240
Ser Leu Pro Phe Ala Glu Gly Ser Ser Ser Val Glu Tyr Ile Asn Asn
245 250 255
Trp Glu Gln Ala Lys Ala Leu Ser Val Glu Leu Glu Ile Asn Phe Glu
260 265 270
Thr Arg Gly Lys Arg Gly Gln Asp Ala Met Tyr Glu Tyr Met Ala Gln
275 280 285
Ala Cys Ala Gly Asn Arg Val Arg Arg Ser Val Gly Ser Ser Leu Ser
290 295 300
Cys Ile Asn Leu Asp Trp Asp Val Ile Arg Asp Lys Thr Lys Thr Lys
305 310 315 320
Ile Glu Ser Leu Lys Glu His Gly Pro Ile Lys Asn Lys Met Ser Glu
325 330 335
Ser Pro Asn Lys Thr Val Ser Glu Glu Lys Ala Lys Gln Tyr Leu Glu
340 345 350
Glu Phe His Gln Thr Ala Leu Glu His Pro Glu Leu Ser Glu Leu Lys
355 360 365
Thr Val Thr Gly Thr Asn Pro Val Phe Ala Gly Ala Asn Tyr Ala Ala
370 375 380
Trp Ala Val Asn Val Ala Gln Val Ile Asp Ser Glu Thr Ala Asp Asn
385 390 395 400
Leu Glu Lys Thr Thr Ala Ala Leu Ser Ile Leu Pro Gly Ile Gly Ser
405 410 415
Val Met Gly Ile Ala Asp Gly Ala Val His His Asn Thr Glu Glu Ile
420 425 430
Val Ala Gln Ser Ile Ala Leu Ser Ser Leu Met Val Ala Gln Ala Ile
435 440 445
Pro Leu Val Gly Glu Leu Val Asp Ile Gly Phe Ala Ala Tyr Asn Phe
450 455 460
Val Glu Ser Ile Ile Asn Leu Phe Gln Val Val His Asn Ser Tyr Asn
465 470 475 480
Arg Pro Ala Tyr Ser Pro Gly His Lys Thr Gln Pro Phe Leu His Asp
485 490 495
Gly Tyr Ala Val Ser Trp Asn Thr Val Glu Asp Ser Ile Ile Arg Thr
500 505 510
Gly Phe Gln Gly Glu Ser Gly His Asp Ile Lys Ile Thr Ala Glu Asn
515 520 525
Thr Pro Leu Pro Ile Ala Gly Val Leu Leu Pro Thr Ile Pro Gly Lys
530 535 540
Leu Asp Val Asn Lys Ser Lys Thr His Ile Ser Val Asn Gly Arg Lys
545 550 555 560
Ile Arg Met Arg Cys Arg Ala Ile Asp Gly Asp Val Thr Phe Cys Arg
565 570 575
Pro Lys Ser Pro Val Tyr Val Gly Asn Gly Val His Ala Asn Leu His
580 585 590
Val Ala Phe His Arg Ser Ser Ser Glu Lys Ile His Ser Asn Glu Ile
595 600 605
Ser Ser Asp Ser Ile Gly Val Leu Gly Tyr Gln Lys Thr Val Asp His
610 615 620
Thr Lys Val Asn Ser Lys Leu Ser Leu Phe Phe Glu Ile Lys Ser Leu
625 630 635 640
Asn Asn Asn Ile Leu Gly Trp Glu Phe Gly Gly Gly Ala Pro Gln Asn
645 650 655
Gly Ala Ala Glu Asp Lys Lys Thr Glu Tyr Leu Leu Glu Gln Ile Lys
660 665 670
Ile Pro Ser Trp Asp Arg Asn Asn Ile Pro Asp Glu Asn Glu Gln Val
675 680 685
Ile Glu Asp Pro Gln Glu Asp Asn Lys Asp Glu Asp Glu Asp Glu Glu
690 695 700
Thr Glu Thr Glu Asn Leu Glu Thr Glu Asp Asp Asn Asn Glu Glu Leu
705 710 715 720
Glu His His His His His His
725
<210> 87
<211> 709
<212> PRT
<213> 人工序列
<220>
<223> PP23生物融合蛋白
<400> 87
Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala
1 5 10 15
Ala Gln Pro Ala Met Ala Met Gly Leu Asn Asn Asn Ile Leu Gly Trp
20 25 30
Glu Phe Gly Gly Gly Ala Pro Gln Asn Gly Ala Ala Glu Asp Lys Lys
35 40 45
Thr Glu Tyr Leu Leu Glu Gln Ile Lys Ile Pro Ser Trp Asp Arg Asn
50 55 60
Asn Ile Pro Asp Glu Asn Glu Gln Val Ile Glu Asp Pro Gln Glu Asp
65 70 75 80
Asn Lys Asp Glu Asp Glu Asp Glu Glu Thr Glu Thr Glu Asn Leu Glu
85 90 95
Thr Glu Asp Asp Asn Asn Glu Glu Gly Ala Asp Asp Val Val Asp Ser
100 105 110
Ser Lys Ser Phe Val Met Glu Asn Phe Ser Ser Tyr His Gly Thr Lys
115 120 125
Pro Gly Tyr Val Asp Ser Ile Gln Lys Gly Ile Gln Lys Pro Lys Ser
130 135 140
Gly Thr Gln Gly Asn Tyr Asp Asp Asp Trp Lys Glu Phe Tyr Ser Thr
145 150 155 160
Asp Asn Lys Tyr Asp Ala Ala Gly Tyr Ser Val Asp Asn Glu Asn Pro
165 170 175
Leu Ser Gly Lys Ala Gly Gly Val Val Lys Val Thr Tyr Pro Gly Leu
180 185 190
Thr Lys Val Leu Ala Leu Lys Val Asp Asn Ala Glu Thr Ile Lys Lys
195 200 205
Glu Leu Gly Leu Ser Leu Thr Glu Pro Leu Met Glu Gln Val Gly Thr
210 215 220
Glu Glu Phe Ile Lys Arg Phe Gly Asp Gly Ala Ser Arg Val Val Leu
225 230 235 240
Ser Leu Pro Phe Ala Glu Gly Ser Ser Ser Val Glu Tyr Ile Asn Asn
245 250 255
Trp Glu Gln Ala Lys Ala Leu Ser Val Glu Leu Glu Ile Asn Phe Glu
260 265 270
Thr Arg Gly Lys Arg Gly Gln Asp Ala Met Tyr Glu Tyr Met Ala Gln
275 280 285
Ala Cys Ala Gly Asn Arg Val Arg Arg Ser Val Gly Ser Ser Leu Ser
290 295 300
Cys Ile Asn Leu Asp Trp Asp Val Ile Arg Asp Lys Thr Lys Thr Lys
305 310 315 320
Ile Glu Ser Leu Lys Glu His Gly Pro Ile Lys Asn Lys Met Ser Glu
325 330 335
Ser Pro Asn Lys Thr Val Ser Glu Glu Lys Ala Lys Gln Tyr Leu Glu
340 345 350
Glu Phe His Gln Thr Ala Leu Glu His Pro Glu Leu Ser Glu Leu Lys
355 360 365
Thr Val Thr Gly Thr Asn Pro Val Phe Ala Gly Ala Asn Tyr Ala Ala
370 375 380
Trp Ala Val Asn Val Ala Gln Val Ile Asp Ser Glu Thr Ala Asp Asn
385 390 395 400
Leu Glu Lys Thr Thr Ala Ala Leu Ser Ile Leu Pro Gly Ile Gly Ser
405 410 415
Val Met Gly Ile Ala Asp Gly Ala Val His His Asn Thr Glu Glu Ile
420 425 430
Val Ala Gln Ser Ile Ala Leu Ser Ser Leu Met Val Ala Gln Ala Ile
435 440 445
Pro Leu Val Gly Glu Leu Val Asp Ile Gly Phe Ala Ala Tyr Asn Phe
450 455 460
Val Glu Ser Ile Ile Asn Leu Phe Gln Val Val His Asn Ser Tyr Asn
465 470 475 480
Arg Pro Ala Tyr Ser Pro Gly His Lys Thr Gln Pro Phe Leu His Asp
485 490 495
Gly Tyr Ala Val Ser Trp Asn Thr Val Glu Asp Ser Ile Ile Arg Thr
500 505 510
Gly Phe Gln Gly Glu Ser Gly His Asp Ile Lys Ile Thr Ala Glu Asn
515 520 525
Thr Pro Leu Pro Ile Ala Gly Val Leu Leu Pro Thr Ile Pro Gly Lys
530 535 540
Leu Asp Val Asn Lys Ser Lys Thr His Ile Ser Val Asn Gly Arg Lys
545 550 555 560
Ile Arg Met Arg Cys Arg Ala Ile Asp Gly Asp Val Thr Phe Cys Arg
565 570 575
Pro Lys Ser Pro Val Tyr Val Gly Asn Gly Val His Ala Asn Leu His
580 585 590
Val Ala Phe His Arg Ser Ser Ser Glu Lys Ile His Ser Asn Glu Ile
595 600 605
Ser Ser Asp Ser Ile Gly Val Leu Gly Tyr Gln Lys Thr Val Asp His
610 615 620
Thr Lys Val Asn Ser Lys Leu Ser Leu Phe Phe Glu Ile Lys Ser Ser
625 630 635 640
Asn Glu Lys Gly Arg Pro Pro Thr Tyr Ser Pro Ile Leu Asp Asp Gly
645 650 655
Ile Glu Phe Ser Gly Gly Leu Tyr Phe Asn Glu Lys Lys Ser Thr Glu
660 665 670
Glu Asn Lys Gln Lys Asn Val Leu Glu Ser Val Asn Leu Thr Ser Trp
675 680 685
Asp Lys Glu Asp Ile Val Lys Glu Asn Glu Asp Val Lys Leu Glu His
690 695 700
His His His His His
705
<210> 88
<211> 867
<212> PRT
<213> 人工序列
<220>
<223> PP25生物融合蛋白
<400> 88
Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala
1 5 10 15
Ala Gln Pro Ala Met Ala Met Gly Ser Asp Glu Leu Phe Asn Glu Leu
20 25 30
Leu Asn Ser Val Asp Val Asn Gly Glu Val Lys Glu Asn Ile Leu Glu
35 40 45
Glu Ser Gln Val Asn Asp Asp Ile Phe Asn Ser Leu Val Lys Ser Val
50 55 60
Gln Gln Glu Gln Gln His Asn Val Glu Glu Lys Val Glu Glu Ser Val
65 70 75 80
Glu Glu Asn Asp Glu Glu Ser Val Glu Glu Asn Val Glu Glu Asn Val
85 90 95
Glu Glu Asn Asp Asp Glu Ser Val Ala Ser Ser Val Glu Glu Ser Ile
100 105 110
Ala Ser Ser Val Asp Glu Ser Ile Asp Ser Ser Ile Glu Glu Asn Val
115 120 125
Ala Pro Thr Val Glu Glu Ile Val Ala Pro Thr Val Glu Glu Ile Val
130 135 140
Ala Pro Ser Val Val Glu Ser Val Ala Pro Ser Val Glu Glu Ser Val
145 150 155 160
Glu Glu Asn Val Glu Glu Ser Val Ala Glu Asn Val Glu Glu Gly Ala
165 170 175
Asp Asp Val Val Asp Ser Ser Lys Ser Phe Val Met Glu Asn Phe Ser
180 185 190
Ser Tyr His Gly Thr Lys Pro Gly Tyr Val Asp Ser Ile Gln Lys Gly
195 200 205
Ile Gln Lys Pro Lys Ser Gly Thr Gln Gly Asn Tyr Asp Asp Asp Trp
210 215 220
Lys Glu Phe Tyr Ser Thr Asp Asn Lys Tyr Asp Ala Ala Gly Tyr Ser
225 230 235 240
Val Asp Asn Glu Asn Pro Leu Ser Gly Lys Ala Gly Gly Val Val Lys
245 250 255
Val Thr Tyr Pro Gly Leu Thr Lys Val Leu Ala Leu Lys Val Asp Asn
260 265 270
Ala Glu Thr Ile Lys Lys Glu Leu Gly Leu Ser Leu Thr Glu Pro Leu
275 280 285
Met Glu Gln Val Gly Thr Glu Glu Phe Ile Lys Arg Phe Gly Asp Gly
290 295 300
Ala Ser Arg Val Val Leu Ser Leu Pro Phe Ala Glu Gly Ser Ser Ser
305 310 315 320
Val Glu Tyr Ile Asn Asn Trp Glu Gln Ala Lys Ala Leu Ser Val Glu
325 330 335
Leu Glu Ile Asn Phe Glu Thr Arg Gly Lys Arg Gly Gln Asp Ala Met
340 345 350
Tyr Glu Tyr Met Ala Gln Ala Cys Ala Gly Asn Arg Val Arg Arg Ser
355 360 365
Val Gly Ser Ser Leu Ser Cys Ile Asn Leu Asp Trp Asp Val Ile Arg
370 375 380
Asp Lys Thr Lys Thr Lys Ile Glu Ser Leu Lys Glu His Gly Pro Ile
385 390 395 400
Lys Asn Lys Met Ser Glu Ser Pro Asn Lys Thr Val Ser Glu Glu Lys
405 410 415
Ala Lys Gln Tyr Leu Glu Glu Phe His Gln Thr Ala Leu Glu His Pro
420 425 430
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Gln Pro Phe Leu His Asp Gly Tyr Ala Val Ser Trp Asn Thr Val Glu
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Lys Ile Thr Ala Glu Asn Thr Pro Leu Pro Ile Ala Gly Val Leu Leu
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Pro Thr Ile Pro Gly Lys Leu Asp Val Asn Lys Ser Lys Thr His Ile
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Ser Val Asn Gly Arg Lys Ile Arg Met Arg Cys Arg Ala Ile Asp Gly
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Asp Val Thr Phe Cys Arg Pro Lys Ser Pro Val Tyr Val Gly Asn Gly
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Val His Ala Asn Leu His Val Ala Phe His Arg Ser Ser Ser Glu Lys
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690 695 700
Phe Glu Ile Lys Ser Ser Asp Glu Leu Phe Asn Glu Leu Leu Asn Ser
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Val Asp Val Asn Gly Glu Val Lys Glu Asn Ile Leu Glu Glu Ser Gln
725 730 735
Val Asn Asp Asp Ile Phe Asn Ser Leu Val Lys Ser Val Gln Gln Glu
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785 790 795 800
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865
<210> 89
<211> 807
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<213> 恶性疟原虫
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Claims (17)
1.一种融合蛋白，其包括至少一个融合于载体异源蛋白序列的N-末端和/或C-末端的抗原性氨基酸序列，其中所述抗原性序列包括疟原虫属(Plasmodium)蛋白的表位序列且所述载体异源蛋白序列是在人类中具有免疫原性的序列。
2.权利要求1的融合蛋白，其中所述载体异源蛋白序列选自：白喉类毒素的交叉反应材料(CRM)、白喉类毒素(D)、无毒突变重组铜绿假单胞菌(Pseudomonas aeruginosa)胞外蛋白A(repA)、脑膜炎球菌外膜蛋白复合物(OMPC)、破伤风类毒素(T)、流行性感冒嗜血杆菌(H.influenza)蛋白D(hiD)及其免疫原性片段，其中所述载体异源蛋白序列优选为CRM197或其免疫原性片段，所述片段优选地选自：CRM197的片段A、跨膜结构域T、受体结合结构域R、CRM197的氨基酸序列1至190和CRM197的氨基酸序列1至389。
3.权利要求1或2任一项的融合蛋白，其中所述抗原性序列是由红细胞阶段的疟原虫属表达的抗原性蛋白或其表位片段。
4.权利要求3的融合蛋白，其中所述抗原性序列选自：MSP3、LSA5(也称为PEBS或11-1的子区)、Glurp R0和R2、SERP、P27和P27A、P45、P90和P77、P14、P181、MSP1-区2、MSP2、GBP130、蛋白质332、蛋白质11-1、MSP4或其任何表位片段，其中所述抗原性序列优选为MSP3或其表位片段，所述片段优选地涵盖选自MSP3-1、MSP3-2、MSP3-3、MSP3-4、MSP3-7和MSP3-8，优选为MSP3-1的疟原虫属MSP3蛋白的C-末端区域的基序a、b、c、d、e和/或f。
5.权利要求1或2任一项的融合蛋白，其中所述抗原性序列是由红细胞前阶段的疟原虫属表达的抗原性蛋白或其表位片段。
6.权利要求5的融合蛋白，其中所述抗原性序列选自：LSA3、LSA5(也称为PEBS或11-1的子区)、CS、Trap和Salsa及其任何表位片段。
7.权利要求1或2任一项的融合蛋白，其中所述抗原性序列选自：Pf25、Pf45/48、Rh5、AMA1、MSP1-19、MSP1-42、MSP2、MSP4-5、Var CSA及其任何表位片段。
8.权利要求1-6任一项的融合蛋白，其包括作为抗原性序列的MSP3，优选为MSP3-1、LSA3、LSA5或其表位片段，所述抗原性序列融合至作为载体序列的CRM197或其免疫原性片段。
9.权利要求1-8任一项的融合蛋白，其包括两个各自位于所述载体蛋白序列的C-末端和N-末端或皆位于相同末端的抗原性序列。
10.权利要求1-8任一项的融合蛋白，其中所述至少一个氨基酸序列通过肽连接体连接于所述载体异源蛋白序列的N-末端和/或C-末端，其中所述肽连接体优选为1至35个氨基酸，优选为5至20个氨基酸的序列。
11.权利要求10的融合蛋白，其中所述肽连接体是(Gly-Gly-Gly-Gly-Ser)n、(Gly)n或(EAAAK)n，其中n为1至4，优选为1至3。
12.一种核酸构建体，其编码如权利要求1至11任一项所定义的融合蛋白。
13.一种载体，其在表达盒中包括权利要求12的核酸构建体。
14.一种宿主细胞，其中已插入权利要求13的载体。
15.一种用于制备如权利要求1至11任一项所定义的融合蛋白的体外方法，所述方法包括使权利要求14的宿主细胞在诱导如权利要求12所定义的核酸构建体表达的条件下繁殖，和收集如此表达的所述融合蛋白。
16.一种疫苗，其包括如权利要求1至11任一项所定义的融合蛋白、或至少两种分别包括至少两个不同抗原性氨基酸序列的如权利要求1至11任一项所定义的融合蛋白的组合、或如权利要求12所定义的编码所述融合蛋白的核酸构建体，与生理上可接受的媒剂。
17.权利要求16的疫苗，其用于对人类对象接种疫苗来对抗疟疾。
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| EP16180544 | 2016-07-21 | ||
| EP16180544.5 | 2016-07-21 | ||
| PCT/SG2017/050369 WO2018017020A1 (en) | 2016-07-21 | 2017-07-21 | Biofusion proteins as anti-malaria vaccines |
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| CN109963586B CN109963586B (zh) | 2023-11-03 |
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| EP (2) | EP4147715A1 (zh) |
| JP (2) | JP2019526274A (zh) |
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| CN (1) | CN109963586B (zh) |
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| CN111135290A (zh) * | 2020-01-16 | 2020-05-12 | 定山石生物科技(北京)有限公司 | 一种用于激活人体免疫细胞的多肽试剂 |
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| EP3823668A1 (en) | 2018-07-16 | 2021-05-26 | DCPrime B.V. | A combination product for use in tumor vaccination |
| WO2020033398A1 (en) * | 2018-08-06 | 2020-02-13 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for treating atii cell-dependent lung diseases |
| AU2019383548A1 (en) * | 2018-11-23 | 2021-06-24 | Strike Pharma Ab | Bi-specific conjugates |
| CA3133410A1 (en) | 2019-04-25 | 2020-10-29 | Dcprime B.V. | Methods of tumor vaccination |
| NL2023863B1 (en) * | 2019-09-20 | 2021-05-25 | Univ Griffith | Protein particles and uses thereof |
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| CN102807621A (zh) * | 2011-06-01 | 2012-12-05 | 厦门大学 | 包含白喉毒素无毒突变体crm197或其片段的融合蛋白 |
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| CA2363118A1 (en) * | 1999-02-25 | 2000-08-31 | Smithkline Beecham Biologicals S.A. | Immunogens comprising a peptide and a carrier derived from h.influenzae protein d |
| DK200201741A (da) * | 2002-11-12 | 2003-09-16 | Statens Seruminstitut | Vaccine comprising chimeric malaria proteins derived from Plasmodium falciparum |
| TWI379839B (en) * | 2003-12-17 | 2012-12-21 | Wyeth Llc | Aβ immunogenic peptide carrier conjugates and methods of producing same |
| CA2903716C (en) * | 2013-03-08 | 2019-04-09 | Pfizer Inc. | Immunogenic fusion polypeptides |
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| CN111135290A (zh) * | 2020-01-16 | 2020-05-12 | 定山石生物科技(北京)有限公司 | 一种用于激活人体免疫细胞的多肽试剂 |
Also Published As
| Publication number | Publication date |
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| WO2018017020A1 (en) | 2018-01-25 |
| KR20190090775A (ko) | 2019-08-02 |
| EP4147715A1 (en) | 2023-03-15 |
| TWI780058B (zh) | 2022-10-11 |
| CN109963586B (zh) | 2023-11-03 |
| US20210038706A1 (en) | 2021-02-11 |
| CA3031399A1 (en) | 2018-01-25 |
| EP3487526A1 (en) | 2019-05-29 |
| EP3487526B1 (en) | 2022-07-06 |
| TW201803907A (zh) | 2018-02-01 |
| US20220409712A1 (en) | 2022-12-29 |
| BR112019001115A2 (pt) | 2019-06-25 |
| JP2019526274A (ja) | 2019-09-19 |
| AU2017300965A1 (en) | 2019-02-07 |
| JP2022116169A (ja) | 2022-08-09 |
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