CN107532152A - 用于测量血糖水平的组合物和方法 - Google Patents

用于测量血糖水平的组合物和方法 Download PDF

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CN107532152A
CN107532152A CN201580075732.XA CN201580075732A CN107532152A CN 107532152 A CN107532152 A CN 107532152A CN 201580075732 A CN201580075732 A CN 201580075732A CN 107532152 A CN107532152 A CN 107532152A
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C·H·格特曼
D·巴拉姆
D·奥默
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Intelligent Enzyme Biological Medicine Co Ltd
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Intelligent Enzyme Biological Medicine Co Ltd
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Priority claimed from PCT/IB2015/002431 external-priority patent/WO2016087937A2/en
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Abstract

在一些实施方案中,本发明提供了一种包含以下序列的氨基酸的蛋白:L(X)n=14X3(X)n=1X1(X)n‑1E(X)n‑4P(X)n‑1NR(X)n‑3S(X)n‑4D(X)n‑2G(X)n‑7Y(X)n‑4(X)n=32‑34X2,其中每个X独立地表示任何天然存在的氨基酸残基,n表示由在该位置相应的圆括号表示的氨基酸残基的数目,其中:a)X1选自S,C,T,M,V,Y,N,P,L,G,Q,A,I,D,W,H或E,其中如果X1是L,H或V,则X3是D;和/或b)X2选自H,L,S或V。在一些实施方案中,本发明还提供包含SEQ ID NO:38或SEQ ID NO:39所述的序列的氨基酸的蛋白,不同之处在于:406位置的氨基酸是除F以外的氨基酸;和/或474位置的氨基酸是除N以外的氨基酸。

Description

用于测量血糖水平的组合物和方法
相关申请的交叉引用
本申请要求于2014年12月4日提交的题为“用于测量血糖水平的组合物和方法”的美国临时申请美国专利申请号62/087,297的优先权,其全部内容通过引用并入本文用于所有目的。
技术领域
在一些实施方案中,本发明涉及用于测量血糖水平的组合物和方法。
背景技术
血液葡萄糖监测是测量血液中葡萄糖(血糖)的浓度的方法。在治疗糖尿病中特别重要的是,通过刺穿皮肤(通常是手指上的皮肤)抽血然后将血液涂敷于化学活性的一次性“测试条”来进行血液葡萄糖测量。该测试通常称为毛细血管血糖。目前的教导建议糖尿病患者根据个体情况的性质和严重程度每天测量两至七次血糖水平。根据测量的血糖水平所观察到的模式,患者和医师一起调整饮食、运动和胰岛素摄入量,以更好地控制该疾病。该信息应立即提供给患者。
生物传感器是利用生物材料(诸如微生物、酶和抗体)的分子识别能力来应用生物材料作为分子识别元件的传感器。具体而言,生物传感器利用当固定的生物材料识别目标特定成分时发生的反应,例如通过微生物呼吸的氧消耗、酶反应或发光。在生物传感器中,酶传感器已经在实际应用中取得进展,例如,用于葡萄糖的酶传感器通过由包含在作为试样的样品溶液中的酶和底物之间的反应产生的电子来还原电子受体,以及一种测量装置电化学地测量电子受体的氧化还原量,从而执行样品的定量分析。第一代电化学葡萄糖生物传感器依赖于通过半透透析膜包裹在氧电极上的薄层葡萄糖氧化酶(GOX)。基于对酶催化反应消耗的氧的监测进行测量(Wang 2008)。第二代和第三代生物传感器也依赖于酶催化反应的作用来测定葡萄糖水平(Ferri等人,2011年)。
发明内容
在一些实施方案中,本发明提供了包含以下序列的氨基酸的蛋白:L(X)n=14X3(X)n=1X1(X)n=1E(X)n=4P(X)n=1NR(X)n=3S(X)n=4D(X)n=2G(X)n=7Y(X)n=4Y(X)n=32-34X2,其中每个X独立地表示任何天然存在的氨基酸残基,n表示由各自在该位置的圆括号表示的氨基酸残基的数目,其中:a)X1选自由S,C,T,M,V,Y,N,P,L,G,Q,A,I,D,W,H或E组成的组,其中如果X1是L,H或V,则X3是D;和/或b)X2选自由H,L,S或V组成的组。
在一些实施方案中,本发明还提供包含SEQ ID NO:38或SEQ ID NO:39所述的序列的氨基酸的蛋白,不同之处在于:406位置的氨基酸是除F以外的氨基酸;和/或474位置的氨基酸是除N以外的氨基酸。
附图说明
将参考附图进一步说明本发明,其中在几个视图中,相同的结构由相同的附图标记表示。所示的附图未必按比例绘制,而重点通常放在说明本发明的原理上。此外,一些特征可能被放大以示出特定组件的细节。
图1A示出了本发明的实施方案的一些方面,通过绘制葡萄糖、麦芽糖和木糖的吸光度与反应时间关系,示出野生型FAD-GDHα(SEQ ID NO:1)的活性。图1B通过绘制葡萄糖、麦芽糖和木糖的吸光度与反应时间的关系,示出了突变型FAD-GDHα(SEQ ID NO:8)的活性。
图2和3示出了FAD-GDHα和如SEQ ID NO:8所述的点突变(例如,M318T和R369H)的本发明蛋白模型的实施方案的一些方面。
图4A和4B示出了本发明的实施方案的一些方面,其示出了描述几种FAD-GDHα(来自洋葱伯克氏菌)蛋白的相对活性的图(4A)和表格(4B)。
图5A-5B示出了本发明的实施方案的一些方面,其示出了本发明的一些实施方案的几条曲线,表明酶的提高的灵敏度(图5A)和提高的特异性(图5B)。
图6A示出了本发明的实施方案的一些方面,其示出了非线性模型FAD-GDHα(S330G和N474S)(来自洋葱伯克氏菌),图6B是具有与图6A有关的量化数据的表格。图6C是基于葡萄糖氧化酶测定结构的FAD-GDH(S330G和N474S)α亚基的同源性模型。
图7A示出了本发明的实施方案的一些方面,其示出了非线性模型FAD-GDHαT521A(来自洋葱伯克氏菌),图7B是具有与图7A有关的量化数据的表格。图7C是基于葡萄糖氧化酶测定结构的FAD-GDH T521Aα亚基的同源性模型。
图8A示出了本发明的一些实施方案的一些方面,其示出了非线性拟合FAD-GDHαF406L(来自洋葱伯克氏菌),图8B是具有与图8A相关的量化数据的表格。图8C是基于葡萄糖氧化酶测定结构的FAD-GDH F406Lα亚基的同源性模型。
图9示出了本发明的一些实施方案的一些方面,其示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来进行的突变型酶动力学范围的线性的评估。R2值=0.979,a=17.25,b=80.9nA。
图10示出了本发明的突变型24的一些实施方案的一些方面,其示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来进行的突变型酶动力学范围的线性的评估。R2值=0.938,a=25.3,b=158.23nA。
图11示出了本发明的一些实施方案的一些方面,其示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来进行的突变型酶动力学范围的线性的评估。R2值=0.744,a=16.68,并且b=211nA。
图12是本发明一些实施方案的一些方面的表格,其概述了突变位置以及酶的性质和生物电化学性质(X100Y表示位置100处的残基“X”突变为残基“Y”)。
图13A-E示出了与本发明的组合物相关的所收集的数据的表格。图13A描述了406突变型的生化和电化学参数。图13B将406突变型的生化动力学特征表示成对野生型(100%)的百分比。图13C描述了406突变型的生化选择性和电化学线性和电流,表示成对野生型(100%)的百分比。图13D描述了474突变型对葡萄糖和木糖的生化活性速率。图13E描述了474突变型对葡萄糖和木糖的生化活性速率,表示成对野生型(100%)的百分比。如本文所用,“选择性”可以指蛋白的亲和力,其中蛋白选择结合和/或催化一种底物而不是第二底物--通过说明的方式,但不限于,FAD-GDHα以比木糖更高的速率结合和/或催化葡萄糖。如本文所用,“生化活性”可以指由蛋白介导的任何功能,例如但不限于酶的催化活性。
图14和15示出了本发明的一些实施方案的一些方面。图14示出了FAD-GDHαN474L对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图15示出了N474L对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图16A和16B示出了本发明的一些实施方案的方面。图16A示出了FAD-GDHαN474V对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图16B示出FAD-GDHαN474V对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图17A和17B示出了本发明的一些实施方案的一些方面。图17A示出了FAD-GDHαN474H对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图17B示出了FAD-GDHαN474H对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图18A和18B示出了本发明的一些实施方案的一些方面。图18A示出了FAD-GDHαN474S对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图18B示出了FAD-GDHαN474S对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图19A和19B示出了本发明的一些实施方案的一些方面。图18A示出了FAD-GDHαN474A对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图20示出了概述本发明的组合物的一些实施方案的表格。
图21A和21B示出了本发明的一些实施方案的一些方面。图21B示出了FAD-GDHαF406L对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图21B示出了F406L对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图22示出了本发明的组合物的实施方案的一些方面,其示出了与FAD-GDHαF406L有关的电化学数据。
图23A-24C示出了本发明的一些实施方案的一些方面。图23A示出了FAD-GDHαF406A对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图23B示出F406A对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406A酶活性。图23C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图24A-C示出了本发明的一些实施方案的一些方面。图24A示出FAD-GDHαF406C对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图24B示出F406C对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406C酶活性。图24C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图25A-C示出了本发明的一些实施方案的方面。图25A示出FAD-GDHαF406E对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图25B示出了F406E对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406E酶活性。图25C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图26A-C示出了本发明的一些实施方案的一些方面。图26A示出FAD-GDHαF406D对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图26B示出了F406D对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406D酶活性。图26C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图27A-C示出了本发明的一些实施方案的一些方面。图27A示出了FAD-GDHαF406G对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图27B示出了F406G对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406G酶活性。图27C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图28A和28B示出了本发明的一些实施方案的方面。图28A示出了FAD-GDHαF406H对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图28B示出了F406H对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图29A-C示出了本发明的一些实施方案的一些方面。图29A示出了FAD-GDHαF406I对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图29B示出了F406I对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406I酶活性。图29C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图30A和30B示出了本发明的一些实施方案的一些方面。图30A示出了FAD-GDHαF406M对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图30B示出了F406M对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406M酶活性。
图31A-C示出了本发明的一些实施方案的一些方面。图31A示出了FAD-GDHαF406N对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图31B示出了F406N对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406N酶活性。图31C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图32A和32B示出了本发明的一些实施方案的一些方面。图32A示出了FAD-GDHαF406Q对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图32B示出了F406Q对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图33A-C示出了本发明的一些实施方案的一些方面。图33A示出了FAD-GDHαF406S对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图33示出了F406S对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406S酶活性。图33C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图34A-C示出了本发明的一些实施方案的一些方面。图34A示出了FAD-GDHαF406T对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图34B示出了F406T对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406T酶活性。图34C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图35A-B示出消极结果。图35A示出了FAD-GDHαF406W对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图35B示出了F406W对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。
图36A-C示出了本发明的一些实施方案的一些方面。图36A示出了FAD-GDHαF406Y对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图36B示出了F406Y对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406Y酶活性。图36C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图37A-C示出了本发明的一些实施方案的一些方面。图37A示出了FAD-GDHαF406V对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图37B示出了F406V对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406V酶活性。图37C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图38A-C示出了本发明的一些实施方案的一些方面。图38A示出了FAD-GDHαF406P对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图38B示出F406P对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406P酶活性。图38C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图39示出了与野生型FAD-GDHα蛋白有关的电化学数据。
图40示出了本发明的组合物的实施方案的电化学数据表。406位置的突变在生理范围的整个范围内提供提高的线性:F406-S/C/T/V/Y/N/P/L/G/A/I/D/E。
图41示出了本发明的一些实施方案的一些方面。406位置的突变提供提高的葡萄糖选择性:F406-S/C/T/M/V/Y/N/P/L/G/Q/A/I/D/H/E。F406W提供了降低酶对葡萄糖的选择性的取代型的实例。
图42A至42C示出了多种不同FAD-GDHα蛋白的序列排列。对于一致性序列,大写表示同一性(identity),小写表示大于0.5的一致性水平,!是I或V中的任何一个,$是L或M中的一个,%是F或Y中的任何一个,#是NDQEBZ中的任何一个。
在已经公开的这些有益效果和改进之中,通过结合附图的以下描述,本发明的其它目的和优点将变得明显。本文公开了本发明的详细实施方案;然而,应当理解,所公开的实施方案仅仅是可以以各种形式实施的本发明的说明。另外,结合本发明的各种实施方案给出的每个实施例旨在说明而不是限制性的。
具体实施方式
将参考附图进一步说明本发明,其中在几个视图中,相同的结构由相同的附图标记表示。所示的附图未必按比例绘制,相反,重点一般放在说明本发明的原理上。此外,一些特征可能被放大以示出特定部件的细节。
这些附图构成本说明书的一部分,并且包括本发明的说明性实施方案并且说明了其各种目的和特征。此外,附图未必按比例绘制,某些特征可能被放大以示出特定部件的细节。此外,附图中所示的任何测量、规格等旨在是说明性的,而不是限制性的。因此,本文公开的具体结构和功能细节不应被解释为限制性的,而是仅作为教导本领域技术人员以各种方式应用本发明的代表性基础。
在整个说明书和权利要求书中,以下术语具有与本文明确相关的含义,除非上下文另有明确规定。在本文中使用的短语“在一个实施方案中”和“在一些实施方案中”未必指代相同的实施方案,尽管它可以指代相同的实施方案。此外,在本文中使用的短语“在另一个实施方案”和“在某些其他实施方案中”未必指代不同的实施方案,尽管它可以指代不同的实施方案。因此,如下所述,在不脱离本发明的范围或精神的情况下,可以容易地组合本发明的各种实施方案。
此外,在整个说明书中,“一个”、“一种”和“所述”的含义包括复数引用。“在…中”的含义包括“在…中”和“在…上”。
如本文所用,“线性”是指对于底物浓度和测量电流之间的关系曲线计算的线性拟合的R2值。在一些实施方案中,良好的线性被认为是在生理葡萄糖水平(0-600mg/dL)的整个范围内等于或高于0.85的R2值。在一些实施方案中,良好的线性被认为是在生理葡萄糖水平的整个范围内等于或高于0.9的R2值。在一些实施方案中,良好的线性被认为是在生理葡萄糖水平的整个范围内等于或高于0.95的R2值。葡萄糖感测装置使用基于线性的算法将测量的电流转换为葡萄糖水平。因此,葡萄糖感测酶的线性范围提高了血糖浓度的测量精度。
黄素蛋白葡萄糖脱氢酶(FAD-GDH,EC 1.1.5.9)最近被用作葡萄糖测试条中的葡萄糖感测酶。FAD-GDH通过使用各种电子受体(诸如二氯苯酚靛酚)催化葡萄糖的氧化。
迄今为止,已经从革兰氏阴性细菌(洋葱伯克霍尔德菌)、真菌(曲霉属(Aspergillus sp.)、米曲霉(A.oryzae)、黑曲霉(A.niger)、土曲霉(A.terreus))和昆虫(黑腹果蝇(Drosophila melanogaster)、冈比亚按蚊(Anopheles gambiae)、意蜂(Apismellifera)、赤拟谷盗(Tribolium castaneum))分离出FAD-GDH。
蛋白由三个亚基组成:在其氧化还原中心处含有FAD的催化亚基(α,67kDa)、多血红素(multiheme)电子转移亚基(β,43kDa)和伴侣亚基(γ,20kDa)。α亚基可以独立于其他亚基也可以与β和γ亚基一起在大肠杆菌中重组表达并纯化,同时保持两种情况下的催化活性。FAD-GDH是一种在电子受体诸如2,6-二氯苯酚靛酚或铁氰化钾的存在下催化葡萄糖氧化的酶。FAD-GDH可用于分析物检测试验。FAD-GDH由多个亚基组成,包括催化亚基α。
在一些实施方案中,本发明的FAD-GDH,包括本发明中描述的所有突变型,可以与β(β)亚基(细胞色素结构域)连续地或在不同质粒上表达,表达并纯化以产生可以将改进的电子转移递送到各种生物传感器应用的蛋白。在一些实施方案中,本发明的FAD-GDH可以在没有β(β)亚基的情况下表达并且纯化,如下面进一步描述的。
在一些实施方案中,分析物检测试验,例如葡萄糖检测试验,可以基于过氧化氢的产生及其随后的检测。例如,通过使用葡萄糖氧化酶首先氧化葡萄糖以产生葡萄糖酸和过氧化氢的试验来定量葡萄糖。所得到的过氧化氢与过氧化物酶结合导致一种或多种有机底物(即指示剂)转化为显色产物,然后检测该产物并与初始样品中的葡萄糖浓度相关。
在本发明中,本发明人使α亚基突变,并使其与天然γ亚基共表达。本发明的人工突变的FAD-GDHα亚基可以与天然的或突变的γ亚基、β亚基或两者共表达。
在一些实施方案中,本发明提供了包含以下序列的氨基酸的蛋白:L(X)n=14X3(X)n=1X1(X)n=1E(X)n=4P(X)n=1NR(X)n=3S(X)n=4D(X)n=2G(X)n=7Y(X)n=4Y(X)n=32-34X2,其中每个X独立地表示任何天然存在的氨基酸残基,n表示由在该位置各自的圆括号表示的氨基酸残基的数目,其中:a)X1选自S,C,T,M,V,Y,N,P,L,G,Q,A,I,D,W,H或E,其中如果X1是L,H或V,则X3是D;和/或b)X2选自H,L,S或V。在一个实施方案中,蛋白包含以下序列:(X)n=3-11D(X)n=1V(X)n=2G(X)n=1G(X)n=2G(X)n=3A(X)n=5AG(X)n=2V(X)n=2LE(X)n=1GP(X)n=3R(X)n=3V(X)n=2FR(X)n=4K(X)n=5P(X)n=1P(X)n=4A(X)n=2P(X)n=5-6N(X)n=1YL(X)n=3G(X)n=7-9Y(X)n=1R(X)n=2GGT(X)n=1WHWA(X)n=4R(X)n=2P(X)n=1D(X)n=6YG(X)n=2RDW(X)n=3Y(X)n=3E(X)n=2Y(X)n=2AE(X)n= 3GV(X)n=1G(X)n=5-9SPR(X)n=4P(X)n=23-25V(X)n=6RN(X)n=3YD(X)n=1RP(X)n=1C(X)n=1G(X)n= 1NNCMP(X)n=1CP(X)n=2A(X)n=1Y(X)n=1G(X)n=6A(X)n=2AG(X)n=6AVV(X)n=3E(X)n=8-9A(X)n=2Y(X)n=1D(X)n=5HRV(X)n=5V(X)n=2A(X)n=3E(X)n=2K(X)n=4S(X)n=5P(X)n=1G(X)n=2N(X)n=5GRN(X)n=1MDH(X)n=4V(X)n=1F(X)n=6-7W(X)n=1GRGP(X)n=9RDG(X)n=2R(X)n=19T(X)n=12-14L(X)n=14X3(X)n=1X1(X)n=1E(X)n=4P(X)n=1NR(X)n=3S(X)n=4D(X)n=2G(X)n=7Y(X)n=4Y(X)n=32-34X2(X)n=2H(X)n=2G(X)n=3MG(X)n=5SV(X)n=1D(X)n=9NL(X)n=12T(X)n=1N(X)n=1TLT(X)n=2AL(X)n=1L(X)n=3D(X)n=2-6。本领域普通技术人员将理解,为了根据本发明产生具有黄素腺嘌呤二核苷酸-葡萄糖脱氢酶α亚基(FAD-GDHα)活性的蛋白,人们将基于天然存在的FAD-GDHα蛋白的氨基酸序列选择这种蛋白的氨基酸残基。上述序列中指定的氨基酸残基(即未表示为“X”的那些残基)表示在FAD-GDHα蛋白中保留的残基。这样的残基作为参考点,以更好地为本领域普通技术人员指定天然存在的FAD-GDHα中的氨基酸残基(即本文中表示为“X1”和“X2”的氨基酸残基)的位置,其可以突变以产生具有改进性质的非天然存在的FAD-GDHα蛋白。
在一些实施方案中,本发明的FAD-GDHα蛋白包括氨基酸序列(例如如表2所示的SEQ ID NO:3-8)的至少一个突变(例如,点突变)。在一些实施方案中,突变位于FAD-GDHα的甲硫氨酸43。在一些实施方案中,突变位于FAD-GDHα的异亮氨酸346。在一些实施方案中,突变位于FAD-GDHα的丝氨酸420。在一些实施方案中,突变位于FAD-GDHα的丝氨酸365。在一些实施方案中,突变位于FAD-GDHα的甘氨酸208。在一些实施方案中,突变位于FAD-GDHα的苏氨酸521。在一些实施方案中,突变位于FAD-GDHα的缬氨酸306。在一些实施方案中,突变位于FAD-GDHα的谷氨酰胺412。在一些实施方案中,突变位于FAD-GDHα的精氨酸416。在一些实施方案中,突变位于FAD-GDHα的天冬酰胺215。在一些实施方案中,突变位于FAD-GDHα的丙氨酸487。在一些实施方案中,突变位于FAD-GDHα的天冬酰胺116。在一些实施方案中,突变位于FAD-GDHα的甲硫氨酸219。在一些实施方案中,突变位于FAD-GDHα的天冬氨酸440。在一些实施方案中,突变位于FAD-GDHα的丝氨酸330。在一些实施方案中,突变位于FAD-GDHα的脯氨酸257。在一些实施方案中,突变位于FAD-GDHα的天冬酰胺474。在一些实施方案中,突变位于FAD-GDHα的苏氨酸521。在一些实施方案中,突变位于FAD-GDHα的丝氨酸420。在一些实施方案中,突变位于FAD-GDHα的丝氨酸365。在一些实施方案中,突变位于FAD-GDHα的异亮氨酸261。在一些实施方案中,突变位于FAD-GDHα的苏氨酸521。在一些实施方案中,突-变位于FAD-GDHα的脯氨酸173。在一些实施方案中,突变位于FAD-GDHα的甲硫氨酸219。在一些实施方案中,突变位于FAD-GDHα的天冬氨酸301。在一些实施方案中,突变位于FAD-GDHα的苯丙氨酸353。在一些实施方案中,突变位于FAD-GDHα的苏氨酸521。在一些实施方案中,突变位于FAD-GDHα的苯丙氨酸406。在一些实施方案中,FAD-GDHα具有至少一个突变(例如1个突变,2个突变,3个突变,4个突变,5个突变,6个突变,7个突变,8个突变,9个突变,10个突变,11个突变,12个突变,13个突变,14个突变,15个突变等)。在一些实施方案中,FAD-GDHα具有至少两个突变(例如,2个突变,3个突变,4个突变,5个突变,6个突变,7个突变,8个突变,9个突变,10个突变,11个突变,12个突变,13个突变,14个突变,15个突变等)。在一些实施方案中,突变是点突变。在一些实施方案中,FAD-GDHα的天冬酰胺475未突变。
人工突变的FAD-GDHα蛋白是指与天然存在的FAD-GDHα蛋白具有至少一个氨基酸差异的FAD-GDHα蛋白。在一些实施方案中,本发明是蛋白,其包括:人工突变的FAD-GDHα蛋白,其包括至少一个突变,其中至少一个突变(例如但不限于1个突变,2个突变,3个突变,4个突变,5个突变,6个突变,7个突变,8个突变,9个突变,10个突变,11个突变,12个突变,13个突变,14个突变,15个突变等)在SEQ ID NO:38或SEQ ID NO:39的406位置。在一些实施方案中,至少一个突变选自包括以下各项的组:F406S,F406C,F406T,F406M,F406V,F406Y,F406N,F406P,F406L,F406G,F406Q,F406A,F406I,F406D,F406W,F406H和F406E。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少10%(例如但不限于10%,20%,30%,40%,50%,60%,70%,80%,90%,100%等)的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至400%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至350%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至300%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至250%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至200%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至150%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至100%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ IDNO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加10%至50%的生化活性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至400%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至400%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至400%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至400%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加250%至400%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ IDNO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加300%至400%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ IDNO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加350%至400%的生化活性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至350%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至300%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至250%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至250%的生化活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至200%的生化活性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少40%(例如但不限于40%,50%,60%,70%,80%,90%,100%等)的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加40%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ IDNO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ IDNO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加250%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加300%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加350%至400%的选择性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加40%至350%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加40%至300%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加40%至250%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加40%至200%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加40%至150%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加40%至100%的选择性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至350%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至300%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至250%的选择性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少20%(例如但不限于20%,30%,40%,50%,60%,70%,80%,90%,100%等)的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加250%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ IDNO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加300%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加350%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加400%至500%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加450%至500%的线性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至450%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至400%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至350%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至300%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至250%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至200%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至150%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至100%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至50%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至450%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至400%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至350%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ IDNO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至300%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至250%的线性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加250%至300%的线性。
本发明是蛋白,其包括:人工突变的FAD-GDHα蛋白,其包括至少一个突变(例如但不限于1个突变,2个突变,3个突变,4个突变,5个突变,6个突变,7个突变,8个突变,9个突变,10个突变,11个突变,12个突变,13个突变,14个突变,15个突变等),其中至少一个突变在SEQ ID NO:1的474位置。在一些实施方案中,至少一个突变选自由N474H、N474L、N474S和N474V组成的组。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少20%(例如但不限于20%,30%,40%,50%,60%,70%,80%,90%,100%等)的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加250%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加300%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加350%至400%的活性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至350%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至300%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至250%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至200%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至100%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至50%的活性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至400%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至350%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至300%的活性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至250%的活性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少20%(例如但不限于20%,30%,40%,50%,60%,70%,80%,90%,100%等)的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加250%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加300%至400%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ IDNO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加350%至400%的选择性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至350%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至300%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至250%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至200%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至150%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至100%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加20%至50%的选择性。
在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加50%至350%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加100%至300%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至250%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ ID NO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加200%至250%的选择性。在一些实施方案中,人工突变的FAD-GDHα蛋白与包含SEQ IDNO:38或SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加150%至200%的选择性。
在一些实施方案中,本发明的蛋白在SEQ ID NO:38或SEQ ID NO:39的406位置包括至少一个突变,其中SEQ ID NO:38或SEQ ID NO:39的406位置的苯基丙氨酸被除K或R以外的任何氨基酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少95%的序列同一性(例如但不限于95%,96%,97%,98%等)。在一些实施方案中,SEQ ID NO:38或SEQ ID NO:39的406位置的苯基丙氨酸被除K或R以外的任何氨基酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少96%的序列同一性(例如但不限于96%,97%,98%等)。在一些实施方案中,SEQ ID NO:38或SEQ ID NO:39的406位置的苯基丙氨酸被除K或R以外的任何氨基酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少97%的序列同一性(例如但不限于97%,97.5%,98%等)。在一些实施方案中,SEQ ID NO:38或SEQ ID NO:39的406位置的苯基丙氨酸被除K或R以外的任何氨基酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少98%的序列同一性(例如但不限于98%,98.1%,98.2%等)。在一些实施方案中,SEQ ID NO:38或SEQ ID NO:39的406位置的苯基丙氨酸被除K或R以外的任何氨基酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少99%的序列同一性(例如但不限于99%,99.1%,99.2%等)。在一些实施方案中,SEQ ID NO:38或SEQ ID NO:39的406位置的苯基丙氨酸被除K或R以外的任何氨基酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少95%的序列同一性(例如但不限于95%,96%,97%,98%等),其中474位置的天冬酰胺残基被缬氨酸、组氨酸、亮氨酸或丝氨酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少96%的序列同一性(例如但不限于96%,97%,98%等),其中474位置的天冬酰胺残基被缬氨酸、组氨酸、亮氨酸或丝氨酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少97%的序列同一性(例如但不限于97%,97.5%,98%等),其中474位置的天冬酰胺残基被缬氨酸、组氨酸、亮氨酸或丝氨酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少98%的序列同一性(例如但不限于98%,98.1%,98.2%等),其中474位置的天冬酰胺残基被缬氨酸、组氨酸、亮氨酸或丝氨酸取代。
在一些实施方案中,具有至少一个氨基酸突变的突变FAD-GDHα蛋白,与SEQ IDNO:38或SEQ ID NO:39具有至少99%的序列同一性(例如但不限于99%,99.1%,99.2%等),其中474位置的天冬酰胺残基被缬氨酸、组氨酸、亮氨酸或丝氨酸取代。
在一些实施方案中,本发明是与SEQ IDS:9-29,40-66或86-104中任一个具有至少95%的序列同一性的FAD-GDHα蛋白。在一些实施方案中,本发明是与SEQ IDS:9-29,40-66或86-104中任一个具有至少96%的序列同一性的FAD-GDHα蛋白。在一些实施方案中,本发明是与SEQ IDS:9-29,40-66或86-104中任一个具有至少97%的序列同一性的FAD-GDHα蛋白。在一些实施方案中,本发明是与SEQ IDS:9-29,40-66或86-104中任一个具有至少98%的序列同一性的FAD-GDHα蛋白。在一些实施方案中,本发明是与SEQ IDS:9-29,40-66或86-104中任一个具有至少99%的序列同一性的FAD-GDHα蛋白。
在一些实施方案中,本发明是具有1至5个氨基酸突变的SEQ IDs:9-29,40-66或86-104的任一个的FAD-GDHα蛋白。在一些实施方案中,本发明是具有1至10个氨基酸突变的SEQ IDs:9-29,40-66或86-104的任一个的FAD-GDHα蛋白。在一些实施方案中,本发明是具有1至15个氨基酸突变的SEQ IDs:9-29,40-66或86-104的任一个的FAD-GDHα蛋白。本发明的蛋白应理解为包含以这样的SEQ ID NOs描述的氨基酸序列的全长,而不是子集。
在一些实施方案中,本发明是FAD-GDHα蛋白(SEQ ID NO:38或SEQ ID NO:39),其中FAD-GDHα蛋白包括1-15个氨基酸取代,其中至少一个氨基酸取代包括将406位置的苯基丙氨酸取代为除赖氨酸或精氨酸以外的另一个其他的氨基酸的。
在一些实施方案中,本发明是FAD-GDHα蛋白(SEQID:1),其中FAD-GDHα蛋白包括1-15个氨基酸取代,其中至少一个氨基酸取代包含将474位置的苯基丙氨酸取代为组氨酸、亮氨酸、丝氨酸、或缬氨酸。
在一些实施方案中,本发明是用于测量受试者的葡萄糖水平的方法,所述方法包括:使从受试者获得的体液与突变型FAD-GDHα蛋白接触,测量由突变型FAD-GDHα蛋白产生的电流,计算测量的电流以得到葡萄糖水平,或其任何组合。在一些实施方案中,突变型FAD-GDHα蛋白包含1-15个氨基酸取代,包括但不限于SEQ ID NO:38或SEQ ID NO:39的406或474位置。
本发明的氨基酸包括但不限于20种常见的氨基酸。还包括天然存在的和合成的衍生物,例如硒代半胱氨酸。氨基酸还包括氨基酸类似物。氨基酸“类似物”是具有不同构型的氨基酸的化学相关形式,例如异构体,或D-构型而不是L-构型,或具有氨基酸大致尺寸和形状的有机分子,或对肽键所含原子进行修饰以便在聚合成多肽时具有蛋白酶抗性的氨基酸。
本文和权利要求书中定义的短语“氨基酸”和“氨基酸序列”可以包括一种或多种组分,这些组分是包含由该序列指示的20个天然存在的氨基酸中的任何一种或多种的部分或全部残基的氨基酸衍生物和/或氨基酸类似物。例如,在具有一个或多个酪氨酸残基的氨基酸序列中,这些残基中的一个或多个的一部分可以被同源酪氨酸(homotyrosine)取代。
一个字母和三个字母的氨基酸代码(和各自表示的氨基酸)如下:A表示ala(丙氨酸);C表示cys(半胱氨酸);D表示asp(天冬氨酸);E表示glu(谷氨酸);F表示phe(苯丙氨酸);G表示gly(甘氨酸);H表示his(组氨酸);I表示ile(异亮氨酸);K表示lys(赖氨酸);L表示leu(亮氨酸);M表示met(甲硫氨酸);N表示asn(天冬酰胺);P表示pro(脯氨酸);Q表示gln(谷氨酰胺);R表示arg(精氨酸);S表示ser(丝氨酸);T表示thr(苏氨酸);V表示Val(缬氨酸);W表示trp(色氨酸);Y表示tyr(酪氨酸)。
天然存在的残基基于常见的侧链性质分为:(1)疏水性:正亮氨酸,met,ala,val,leu,ile;(2)中性亲水性:cys,ser,thr;(3)酸性:asp,glu;(4)碱性:asn,gln,his,lys,arg;(5)影响链取向的残基:gly,pro;(6)芳香族:trp,tyr,phe。本领域技术人员应理解,可以在蛋白的氨基酸序列中进行某些保守取代。感兴趣的保守取代如表1所示
表1.示例性和优选的氨基酸取代。
在某些实施方案中,本发明还提供了包含本发明的任何FAD-GDHα蛋白的葡萄糖传感器。使用FAD-GDH的葡萄糖传感器是本领域已知的,并且已经在例如美国专利No.8,658,011中进行了描述,其通过引用并入本文。本发明的蛋白可以用于本领域已知的被设计成使用FAD-GDH的任何生物传感器。
在一些实施方案中,本发明还提供包含本发明的FAD-GDHα和固相载体的组合物。这种载体可以是试剂层或试剂测试条的形式。在一些实施方案中,组合物处于干燥或固体状态。用于葡萄糖传感器的试剂层是本领域已知的,并且已经在例如美国专利No.8,658,011中进行了描述。本领域技术人员将理解,本领域中已知的被设计成与FAD-GDH一起使用的任何试剂层可以制成包含本发明的FAD-GDHα蛋白。试剂测试条用于测定生理样品(例如血液)中分析物(例如葡萄糖)的浓度。测试条可以包含多孔基质、分析物氧化信号产生系统的一个或多个成员和至少一种溶血剂。在使用主题测试条进行分析物浓度测定时,将生理样品涂敷于测试条。接下来,对信号产生系统的显色产物的外观进行检测,并与样品中分析物的浓度关联上。
通常,用户将测试条插入测量仪中,并且伸出手指或替代的身体部位以获得血液样本。将抽出的样品涂敷于测试条,并且测量仪读取测试条并测定分析物浓度,然后将其传送给用户。例如,血糖仪将由测试条中的酶反应产生的电流转换成相应的血糖值,该血糖值被示出或以其他方式提供给患者以示出测试时的葡萄糖水平。
在一些实施方案中,本发明还提供了固定在葡萄糖传感器的电极的导电组件上的本发明的FAD-GDHα蛋白。用于葡萄糖传感器的电极是本领域已知的,并且已经在例如美国专利No.7,497,940中描述,其内容通过引用并入本文。本领域技术人员将理解,本领域已知的被设计成与FAD-GDH一起使用的电极可以制成包含本发明的FAD-GDHα蛋白。
在一些实施方案中,本发明还提供了编码本发明的任何蛋白的DNA序列。这样的DNA序列可以根据本领域已知的任何技术来表达。作为非限制性实施例,可以将这样的序列并入载体用于在细胞中表达。术语“载体”是指能够携带并将另一个多核苷酸片段或序列从一个位置(例如,宿主、系统)转移到另一位置的多核苷酸分子,该多核苷酸分子链接至所述另一个多核苷酸片段或序列。该术语包括用于体内或体外表达系统的载体。作为非限制性实施例,载体可以是“质粒”的形式,其指环状的双链DNA环,其通常保持为游离体形式,但也可以整合入宿主基因组中。在一些实施方案中,本发明因此提供了包含编码蛋白的DNA的宿主细胞,以及生产蛋白的方法,该方法包括在有利于生产蛋白的情况下培养宿主细胞,并且回收蛋白。
如图1A所示通过绘制葡萄糖、麦芽糖和木糖的吸光度与反应时间的关系来示出野生型FAD-GDHα(SEQ ID NO:38)的活性的示例性实施方案。
如图1B所示,通过绘制葡萄糖、麦芽糖和木糖的吸光度与反应时间的关系来示出突变的GAD-GDHα的活性的示例性实施方案。
在图2和图3中示出了FAD-GDHα蛋白模型和如SEQ8(例如,M318T和R369H)中所述的点突变的示例性实施方案。
图4A和图4B示出了几种FAD-GDHα(来自洋葱伯克氏菌)突变型(例如,021,022,023,024,025)、野生型酶(洋葱伯克氏菌FAD-GDHα)和阴性对照(不含FAD-GDHα(洋葱伯克氏菌)的细菌裂解物)的相对活性的示例性实施方案。
本文示出了表明酶的提高的灵敏度(图5A)和提高的特异性(图5B)的几条曲线的示例性实施方案。
图6A中示出了非线性模型FAD-GDHα(S330G和N474S)(来自洋葱伯克氏菌)的示例性实施方案。在图6B的表格中示出了与图6A相关的量化数据的示例性实施方案。图6C中示出了基于葡萄糖氧化酶测定结构的FAD-GDHα(S330G和N474S)α亚基的同源性模型的示例性实施方案。
图7A中示出了非线性模型FAD-GDHαT521A(来自洋葱伯克氏菌)的示例性实施方案。在图7B的表格中示出了与图7A相关的量化数据的示例性实施方案。图7C中示出了基于葡萄糖氧化酶测定结构的FAD-GDHαT521Aα亚基的同源性模型的示例性实施方案。
图8A中示出了非线性模型FAD-GDHαF406L(来自洋葱伯克氏菌)的示例性实施方案。图8B的表格中示出了与图8A相关的量化数据的示例性实施方案。图8C中示出了基于葡萄糖氧化酶测定结构的FAD-GDHαF406Lα亚基的同源性模型的示例性实施方案。
图9示出了示例性实施方案,其示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来评估突变型酶动力学范围的线性。
图10示出了示例性实施方案,其示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来评估突变型酶动力学范围的线性(突变型24)。R2值=0.938,a=25.3,b=158.23nA。
图11示出了示例性实施方案,其示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来评估突变型酶动力学范围的线性。
图12的表格示出了突变位置以及酶的性质和生物电化学性质的示例性实施方案(X100Y表示位置100的残基“X”突变为残基“Y”)。
图13A-E的表格示出了关于本发明的组合物收集的数据的示例性实施方案。图13A描述了406突变型的生化和电化学参数。图13B将406突变型的生化动力学特征表示成对野生型(100%)的百分比。图13C描述了406突变型的生化选择性和电化学线性和电流,表示成对野生型(100%)的百分比。图13D描述了474突变型对葡萄糖和木糖的生化活性速率。图13E描述了474突变型对葡萄糖和木糖的生化活性速率,表示成对野生型(100%)的百分比。
图14和15中示出了本发明的组合物的示例性实施方案。图14示出了FAD-GDHαN474L对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图15示出了N474L对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474L酶活性。
图16A和16B示出了本发明的组合物的示例性实施方案。图16A示出了FAD-GDHαN474V对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图16B示出了FAD-GDHαN474V对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474V酶活性。
图17A和17B示出了本发明的组合物的示例性实施方案。图17A示出了FAD-GDHαN474H对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图17B示出了FAD-GDHαN474H对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474H酶活性。
图18A和18B示出了本发明的组合物的示例性实施方案。图18A示出了FAD-GDHαN474S对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图18B示出了FAD-GDHαN474S对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474S酶活性。
图19A和19B示出了本发明的组合物的示例性实施方案。图18A示出了FAD-GDHαN474A对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474A酶活性。
图20的表格概述中示出了本发明的组合物的示例性实施方案。
图21A和21B示出了本发明的组合物的示例性实施方案。图21B示出了FAD-GDHαF406L对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图21B示出了F406L对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406L酶活性。
图22示出了本发明的组合物的示例性实施方案,示出了与FAD-GDHαF406L相关的电化学数据。
图23A-24C示出了本发明的组合物的示例性实施方案。图23A示出了FAD-GDHαF406A对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图23B示出F406A对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406A酶活性。图23C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图24A-C示出了本发明的组合物的示例性实施方案。图24A示出FAD-GDHαF406C对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图24B示出F406C对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406C酶活性。图24C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图25A-C示出了本发明的组合物的示例性实施方案。图25A示出FAD-GDHαF406E对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图25B示出了F406E对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406E酶活性。图25C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图26A-C示出了本发明的组合物的示例性实施方案。图26A示出FAD-GDHαF406D对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图26B示出了F406D对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406D酶活性。图26C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图27A-C示出了本发明的组合物的示例性实施方案。图27A示出了FAD-GDHαF406G对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图27B示出了F406G对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406G酶活性。图27C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图28A和28B示出了本发明的组合物的示例性实施方案。图28A示出了FAD-GDHαF406H对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图28B示出了F406H对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406H酶活性。
图29A-C示出了本发明的组合物的示例性实施方案。图29A示出了FAD-GDHαF406I对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图29B示出了F406I对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406I酶活性。图29C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图30A和30B示出了本发明的组合物的示例性实施方案。图30A示出了FAD-GDHαF406M对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图30B示出了F406M对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406M酶活性。
图31A-C示出了本发明的组合物的示例性实施方案。图31A示出了FAD-GDHαF406N对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图31B示出了F406N对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406N酶活性。图31C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图32A和32B示出了本发明的组合物的示例性实施方案。图32A示出了FAD-GDHαF406Q对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图32B示出了F406Q对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406Q酶活性。
图33A-C示出了本发明的组合物的示例性实施方案。图33A示出了FAD-GDHαF406S对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图33示出了F406S对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406S酶活性。图33C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图34A-C示出了本发明的组合物的示例性实施方案。图34A示出了FAD-GDHαF406T对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图34B示出了F406T对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406T酶活性。图34C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图35A-B示出了本发明的组合物的示例性实施方案。图35A示出了FAD-GDHαF406W对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图35B示出了F406W对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406W酶活性。
图36A-C示出了本发明的组合物的示例性实施方案。图36A示出了FAD-GDHαF406Y对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图36B示出了F406Y对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406Y酶活性。图36C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图37A-C示出了本发明的组合物的示例性实施方案。图37A示出了FAD-GDHαF406V对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图37B示出了F406V对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406V酶活性。图37C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图38A-C示出了本发明的组合物的示例性实施方案。图38A示出了FAD-GDHαF406P对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图38B示出F406P对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406P酶活性。图38C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图39示出了与野生型FAD-GDHα蛋白有关的电化学数据的示例性实施方案。
在图40的列出本发明的组合物的电化学数据的表中示出了示例性实施方案。406位置的突变在生理范围的整个范围内提供提高的线性:F406-S/C/T/V/Y/N/P/L/G/A/I/D/E。
图41中示出了本发明的组合物的示例性实施方案。406位置的突变提供提高的葡萄糖选择性:F406-S/C/T/M/V/Y/N/P/L/G/Q/A/I/D/H/E。F406W提供了降低酶对葡萄糖的选择性的取代型的实施例。
在一些实施方案中,本发明的蛋白可以与表位标签连接,例如,但不限于,HIS标签、6xHIS标签、麦芽糖结合蛋白标签、绿荧光蛋白标签、谷胱甘肽-S-转移酶标签、链霉亲和素标签等。通过使用长度为例如1-n个氨基酸的连接基,可以使该表位标签与蛋白分离。
实施例:突变的FAD-GDH、α亚基(α)、菌株洋葱伯克氏菌:
实施例1:如SEQ ID NO:3所示,FAD-GDHα突变以包括以下点突变:M43T和I346V。
实施例2:如SEQ ID NO:4所示,FAD-GDHα突变以包括以下点突变:S420N、S365F。
实施例3:如SEQ ID NO:5所示,FAD-GDHα突变以包括以下点突变:G208D。
实施例4:如SEQ ID NO:6所示,FAD-GDHα突变以包括以下点突变:T521A。
实施例5:如SEQ ID NO:7所示,FAD-GDHα突变以包括以下点突变:V306A、Q412R和R416C。
实施例6:如SEQ ID NO:8所示,FAD-GDHα突变以包括以下点突变:M318T和R369H。
实施例:生成重组酶
使用容易产生误差的PCR方法产生FAD-GDHα亚基(FADα)的随机点突变,例如GeneGorph II随机诱变试剂盒(Agilent),其具有SEQ ID NOs:30-33中列出的引物。
FADα和FADγ的DNA序列基于编号#AF430844.1(洋葱伯克氏菌)或编号#CP000152.1(广泛伯克氏菌(B.lata)),并且其蛋白序列分别详述为SEQ ID NO:1(洋葱伯克氏菌)和SEQ ID NO:2(广泛伯克氏菌)(对于FADα)。
FADα通过连接依赖性克隆法被克隆到质粒载体(pTrcHis2A)中,该质粒载体通过用NcoI和HindIII限制性内切核酸酶消化而线性化。按照FADγ终止密码子(腺嘌呤)的最后一个核苷酸是FADα起始密码子(腺嘌呤)的第一个核苷酸的方式,连接位置串联并且3′连接至FAD-GDHγ(FADγ)亚基。通过混合不同摩尔比的NcoI和HindIII消化的FADα和pTrcHis2A,在16℃下过夜进行连接。将连接产物转移到DH5α感受态细胞中,并将得到的菌落用于分离DNA,并且分析得到的质粒DNA进行正连接。除pTrcHis2A之外,融合蛋白可以在pET系统质粒(例如pET14,pET15,pET16,pET19-pET30,pET30EK/LIC,pET30 Xa/LIC,pET32-pET42)中表达,但是特异性限制性内切核酸酶位点可能根据质粒载体中可用的相关位点而变化。
在例如但不限于以下各项的细菌菌株中测试pTrcHis2A-FADγ-FADα(pFADα)的蛋白表达和GDH活性:DH5α,BL21,BL21(DE3),BL21-Codon-plus/RIL,BL21(DE3)-Codon-plus/RIL,BL21(DE3)-Rosetta2,但是可以在BL21(DE3)-Rosetta,BL21(DE3)-pLysS,BL21-SI,BL21-AI,BL21-Tuner,BL21-Tuner-pLysS,BL21-Rosetta-Gami,BL21-Rosetta-Gami-pLysS,Lemo21(DE3)中测试。通过在不同的温度设置(20℃,30℃,37℃,也可以在18℃、27℃的温度设置下测试)下将0.1mM-0.5mM异丙基β-D-1-硫代吡喃半乳糖苷(IPTG)加入到具有Luria-Bertani(LB)、Terrific Broth(TB)或自身诱导培养基(基于LB或TB)的细菌培养物中,在半对数期培养密度(600nm处约0.6的OD)诱导蛋白表达。通过使用超声处理和/或使用细胞裂解液和/或均质化进行细胞裂解,并且通过在10-15%丙烯酰胺的十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)分析法观察蛋白谱,在上述过程之后,在该蛋白水平测试蛋白表达水平。还通过监测GDH活性水平来测试蛋白表达水平,GDH活性水平的监测通过将细胞裂解液与反应缓冲溶液(例如pH7或pH6.5)混合、然后在不同葡萄糖浓度下在例如37℃或30℃下孵育而进行,所述反应缓冲溶液含有0.3-0.8mM 2,6-二氯苯酚靛酚(DCIP)和0.3-0.8mM吩嗪甲硫酸盐(PMS)。通过分光光度计在600nm带宽监测GDH活性。
在37℃的600ml TB培养物中开始中型和大型蛋白表达。在对数中期,将IPTG加入到培养基中,同时将温度设定切换至20℃过夜,进行生长蛋白表达诱导。通过在4℃下以6000rpm离心15分钟来收集细胞。将细胞团块重新悬浮于补充有10mM咪唑、蛋白酶抑制剂混合物片剂和10μg DNAse I(裂解缓冲液)的蛋白缓冲液(缓冲溶液(pH7或优选pH6.5)和150-500mM NaCl)中。裂解通过以下方式进行:在15,000PSI细胞压力下通过弗氏细胞压碎器(French press)三次,或5次超声处理阶段(每阶段包括启动30秒,停止30秒),然后以20,000g离心60分钟。可溶性级分(fraction)装载在装有5ml经过裂解缓冲液预先校准的50%Ni-NTA浆液的重力流动柱上。在结合步骤之后是在保持溶液被缓冲(pH7或优选pH6.5))的同时增加咪唑浓度(20、30和40mM)和随之改变盐浓度(150、500和150mM)的三个冲洗步骤。通过在150mM NaCl的存在下将咪唑浓度提高到300mM,同时保持溶液被缓冲(pH7或优选pH6.5)来进行洗脱步骤。通过如前所述的SDS-PAGE分析和600nm处的分光光度计分析来评估洗脱的蛋白的蛋白纯化和GDH活性水平,合并所选的级分,在PBS pH 7.4下透析,浓缩至1-5mg/ml,然后在液氮中速冻或冷冻干燥。
表2.来自洋葱伯克氏菌(SEQ ID NO:1,3-29)和广泛伯克氏菌(SEQ ID NO:2)的FAD-GDHγα的蛋白序列和用于通过易于产生误差的PCR进行随机诱变的引物的DNA序列。每个蛋白序列以可去除的6x-His标签结束。
表3.来自洋葱伯克氏菌(SEQ ID NO:38,SEQ ID NOs:40-66)和广泛伯克氏菌(SEQID NO:39)的FAD-GDHγα的蛋白序列。
表4.具有可移除的6x-His标签的广泛伯克氏菌突变型的FAD-GDHγα的蛋白序列。
表4.广泛伯克氏菌突变型的FAD-GDHγα的蛋白序列。
图4A和4B示出了描绘几个突变型(例如,021,022,023,024,025)、野生型酶(洋葱伯克氏菌FAD-GDHα)和阴性对照(不含FAD-GDHα(洋葱伯克氏菌)的细菌溶解产物)的相对活性的图(4A)和表格(4B)。在整夜蛋白表达、用裂解液进行细胞破裂并且澄清可溶性级分之后,使用突变型酶、野生型细菌FAD-GDHα酶和对照细胞进行活性测定。例如,用含有编码FAD-GDHα酶的DNA(或阴性对照,仅用不含FAD-GDHαDNA插入片段的质粒转化)的质粒转化大肠杆菌。将转化的大肠杆菌样品温育过夜并诱导产生如上述实施方案中所述的FAD-GDHα酶。然后将可溶性级分用于测试活性,如图4A所示。图4B说明了在FAD-GDHα酶内产生的点突变。
图5A-5B示出了几种曲线,表明FAD-GDHα(洋葱伯克氏菌)的提高的灵敏度(图5A)以及FAD-GDHα(洋葱伯克氏菌)的提高的特异性(图5B)。值得注意的是,目前FAD-GDHα在血糖仪的测试条上的应用示出了对木糖的相当非特异性活性。例如:当存在木糖时,FAD-GDHα活性的上限为58mg/dL(浓度测定为100mg/dL);偏差(mg/dL)为103.7,因此%偏差为36.3。
图6A示出了非线性模型FAD-GDHα(S330G和N474S),图6B是具有与图6A相关的量化数据的表。将2μg的FAD-GDHα(S330G and N474S)固定在碳基丝网印刷电极上。该曲线图表示在具有指示的葡萄糖浓度的葡萄糖负荷之后测量的电流。假设单个结合位点(n=1),通过爬山算法(hill algorithm)进行拟合。假设单个结合位点(n=1),通过爬山算法(hillalgorithm)进行拟合(图6B)。从曲线散点图的拟合得出最大电流和米氏常数(Km)。ND,未测定。图6C是基于葡萄糖氧化酶测定结构的FAD-GDHα(S330G和N474S)α亚基的同源性模型。从GOX结构(PDB代码1CF3)在FAD-GDHα亚基模型上的叠加得到FAD-GDHα的分子(空间填充表示)。
图7A示出了非线性拟合FAD-GDHαT521A,图7B是具有与图7A相关的量化数据的表格。将2μg的FAD-GDHαT521A固定在碳基丝网印刷电极上。该曲线图表示在具有指示的葡萄糖浓度的葡萄糖负荷之后测量的电流。假设单个结合位点(n=1),通过爬山算法(hillalgorithm)进行拟合。假设单个结合位点(n=1),通过爬山算法(hill algorithm)进行拟合(图7B)。从曲线散点图的拟合得出最大电流和米氏常数(Km)。ND,未测定。图7C是基于葡萄糖氧化酶测定结构的FAD-GDH T521Aα亚基的同源性模型。从GOX结构(PDB代码1CF3)在FAD-GDHα亚基模型上的叠加得到FAD-GDHα的分子(空间填充表示)。
图8A是示出从FAD-GDHαF406L突变型得到的结果的图。将2μg的FAD-GDHαF406L固定在碳基丝网印刷电极上。该曲线图表示在具有指示的葡萄糖浓度的葡萄糖负荷之后测量的电流。假设单个结合位点(n=1),通过爬山算法(hill algorithm)进行拟合(图8B)。从曲线散点图的拟合得出最大电流和米氏常数(Km)。ND,未测定。图8C是基于葡萄糖氧化酶测定结构的FAD-GDH F406Lα亚基的同源性模型。从GOX结构(PDB代码1CF3)在FAD-GDHα亚基模型上的叠加得到FAD-GDHα的分子(空间填充表示)。
图9示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来评估突变型酶动力学范围的线性。R2值=0.979,a=17.25,b=80.9nA。
图10示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来评估突变型酶动力学范围的突变型24的线性。R2值=0.938,a=25.3,并且b=158.23nA。
图11示出了通过线性拟合整个范围的测量点并且提取拟合的质量(R平方)、斜率(a)和与Y轴的交点(b)来评估突变型酶动力学范围的线性。R2值=0.744,a=16.68,并且b=211nA。
图12是概述突变位置以及酶的性质和生物电化学性质的表格(X100Y表示位置100的残基“X”突变为残基“Y”)。通过线性拟合从葡萄糖浓度0至30mM的数据图测量线性度。
图13A-E示出了与本发明的组合物相关的收集的数据的表格。图13A描述了406突变型的生化和电化学参数。图13B将406突变型的生化动力学特征表示成对野生型(100%)的百分比。图13C描述了406突变型的生化选择性和电化学线性和电流,表示成对野生型(100%)的百分比。图13D描述了474突变型对葡萄糖和木糖的生化活性速率。图13E描述了474突变型对葡萄糖和木糖的生化活性速率,表示成对野生型(100%)的百分比。
图14和15示出了本发明的组合物的一些实施方案。图14示出了FAD-GDHαN474L对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图15示出了N474L对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474L酶活性。
图16A和16B示出了本发明的组合物的一些实施方案。图16A示出了FAD-GDHαN474V对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图16B示出FAD-GDHαN474V对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474V酶活性。
图17A和17B示出了本发明的组合物的一些实施方案。图17A示出了FAD-GDHαN474H对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图17B示出了FAD-GDHαN474H对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474H酶活性。
图18A和18B示出了本发明的组合物的一些实施方案。图18A示出了FAD-GDHαN474S对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图18B示出了FAD-GDHαN474S对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474S酶活性。
图19A和19B示出了本发明的组合物的一些实施方案。图18A示出了FAD-GDHαN474A对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定N474A酶活性。
图20示出了概述本发明的组合物的一些实施方案的表格。
图21A和21B示出了本发明的组合物的一些实施方案。图21B示出了FAD-GDHαF406L对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图21B示出了F406L对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406L酶活性。
图22示出了本发明的组合物的实施方案,其示出了与FAD-GDHαF406L有关的电化学数据。
图23A-24C示出了本发明的组合物的一些实施方案。图23A示出了FAD-GDHαF406A对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图23B示出F406A对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406A酶活性。图23C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图24A-C示出了本发明的组合物的一些实施方案。图24A示出FAD-GDHαF406C对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图24B示出F406C对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406C酶活性。图24C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图25A-C示出了本发明的组合物的实施方案。图25A示出FAD-GDHαF406E对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图25B示出了F406E对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406E酶活性。图25C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图26A-C示出了本发明的组合物的一些实施方案。图26A示出FAD-GDHαF406D对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图26B示出了F406D对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406D酶活性。图26C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图27A-C示出了本发明的组合物的一些实施方案。图27A示出了FAD-GDHαF406G对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图27B示出了F406G对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406G酶活性。图27C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图28A和28B示出了本发明的组合物的一些实施方案。图28A示出了FAD-GDHαF406H对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图28B示出了F406H对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406H酶活性。
图29A-C示出了本发明的组合物的一些实施方案。图29A示出了FAD-GDHαF406I对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图29B示出了F406I对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406I酶活性。图29C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图30A和30B示出了本发明的组合物的一些实施方案。图30A示出了FAD-GDHαF406M对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图30B示出了F406M对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406M酶活性。
图31A-C示出了本发明的组合物的一些实施方案。图31A示出了FAD-GDHαF406N对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图31B示出了F406N对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406N酶活性。图31C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图32A和32B示出了本发明的组合物的一些实施方案。图32A示出了FAD-GDHαF406Q对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图32B示出了F406Q对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406Q酶活性。
图33A-C示出了本发明的组合物的一些实施方案。图33A示出了FAD-GDHαF406S对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图33示出了F406S对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406S酶活性。图33C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图34A-C示出了本发明的组合物的一些实施方案。图34A示出了FAD-GDHαF406T对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图34B示出了F406T对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406T酶活性。图34C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图35A-B示出了不利的结果。图35A示出了FAD-GDHαF406W对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图35B示出了F406W对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406W酶活性。
图36A-C示出了本发明的组合物的一些实施方案。图36A示出了FAD-GDHαF406Y对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图36B示出了F406Y对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406Y酶活性。图36C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图37A-C示出了本发明的组合物的一些实施方案。图37A示出了FAD-GDHαF406V对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图37B示出了F406V对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406V酶活性。图37C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图38A-C示出了本发明的组合物的一些实施方案。图38A示出了FAD-GDHαF406P对不同浓度的葡萄糖(菱形)和木糖(矩形)的生化反应。图38B示出F406P对葡萄糖的生化反应和通过其获得Km(k)和Vmax的非线性拟合。通过监测OD600下二氯苯酚靛酚(DCIP)信号的降低来测定F406P酶活性。图38C示出了表示生物传感器对不同的葡萄糖浓度(示出为菱形)的电流响应的电化学数据,并且跨数据范围的线性拟合由R2值表示。
图39示出了与野生型FAD-GDHα蛋白有关的电化学数据。
图40示出了本发明的组合物的实施方案的电化学数据表。406位置的突变在生理范围的整个范围内提供提高的线性:F406-S/C/T/V/Y/N/P/L/G/A/I/D/E。
图41示出了本发明的组合物的实施方案。406位置的突变提供提高的葡萄糖选择性:F406-S/C/T/M/V/Y/N/P/L/G/Q/A/I/D/H/E。F406W提供了降低酶对葡萄糖的选择性的取代的实施例。
虽然已经描述了本发明的多个实施方案,但是应当理解,这些实施方案仅是说明性的而不是限制性的,并且许多修改对于本领域普通技术人员来说可能变得明显。此外,各种步骤可以以任何期望的顺序进行(并且可以添加任何期望的步骤和/或可以消除任何期望的步骤)。本文提及的所有出版物和其他参考文献通过引用全部并入,如同每个单独的出版物或参考文献被专门且单独地指明通过引用并入本文。本文引用的出版物和参考文献不被认为是现有技术。
参考文献
Wang,Joseph(2008).电化学葡萄糖生物传感器(Electrochemical GlucoseBiosensors).化学综述(Chem.Rev.)2008,108,814-825.
Ferri,Stefano等人(2011).葡萄糖氧化酶和葡萄糖脱氢酶的综述:葡萄糖感应酶的鸟瞰图(Review of Glucose Oxidases and Glucose Dehydrogenases:A Bird′s EyeView of Glucose Sensing Enzymes).糖尿病科学与技术杂志(Journal of DiabetesScience and Technology).第5卷,第5期,2011年9月。
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Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Ala Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 7
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 7
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Ala Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Arg Pro Glu Asn Cys
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 8
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 8
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Thr Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
His Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 9
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 9
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Leu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 10
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 10
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Asp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 11
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 11
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys His His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 12
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 12
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Met His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 13
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 13
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Glu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 14
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 14
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Ser His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 15
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 15
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Thr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 16
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 16
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Tyr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 17
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 17
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Asn His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 18
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 18
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Gln His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 19
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 19
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Cys His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 20
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 20
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Gly His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 21
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 21
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Pro His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 22
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 22
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Ala His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 23
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 23
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Val His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 24
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 24
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Ile His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 25
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 25
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Trp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 26
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 26
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro His Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 27
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 27
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Leu Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 28
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 28
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Ser Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 29
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 29
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Val Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 30
<211> 26
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 30
ccaggcaaat tctgttttat cagacc 26
<210> 31
<211> 23
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 31
caagctggag accgtttaaa ctc 23
<210> 32
<211> 26
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 32
cgctattcag atcctcttct gagatg 26
<210> 33
<211> 24
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 33
gcttctgcgt tctgatttaa tctg 24
<210> 34
<211> 37
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 34
ggtcgtggtc ggatccggtg tggcaggtgc tattgtg 37
<210> 35
<211> 23
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 35
cgttcttatt gcccgaataa acc 23
<210> 36
<211> 21
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 36
cgaagaagcc ctgatgtttg g 21
<210> 37
<211> 25
<212> DNA
<213> 人工序列
<220>
<223> 重组序列
<400> 37
gaagcatggt atctgggcat tgttg 25
<210> 38
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 38
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 39
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 39
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 40
<211> 538
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 40
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Thr Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn Asp
65 70 75 80
Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile Arg
85 90 95
Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg Phe
100 105 110
Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg Asp
115 120 125
Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala Glu
130 135 140
Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr Ser
145 150 155 160
Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe Asn
165 170 175
Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe His
180 185 190
Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly Arg
195 200 205
Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile Gly
210 215 220
Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala Gly
225 230 235 240
Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly Pro
245 250 255
Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala Glu
260 265 270
His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile Glu
275 280 285
Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn Gly
290 295 300
Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His Pro
305 310 315 320
Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly Arg
325 330 335
Gly Pro Gln Glu Met Thr Ser Leu Val Gly Phe Arg Asp Gly Pro Phe
340 345 350
Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser Arg
355 360 365
Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met Lys
370 375 380
Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr Val
385 390 395 400
Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg Ile
405 410 415
Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro Glu
420 425 430
Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His Thr
435 440 445
Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp Val
450 455 460
Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser Thr
465 470 475 480
Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys Arg
485 490 495
Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met Pro
500 505 510
Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala Leu
515 520 525
Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 41
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 41
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Phe Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Asn Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 42
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 42
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 43
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 43
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Ala Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 44
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 44
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Ala Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Arg Pro Glu Asn Cys
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 45
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 45
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Thr Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
His Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 46
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 46
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Leu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 47
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 47
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Asp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 48
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 48
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys His His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 49
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 49
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Met His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 50
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 50
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Glu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 51
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 51
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Ser His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 52
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 52
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Thr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 53
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 53
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Tyr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 54
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 54
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Asn His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 55
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 55
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Gln His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 56
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 56
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Cys His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 57
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 57
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Gly His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 58
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 58
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Pro His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 59
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 59
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Ala His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 60
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 60
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Val His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 61
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 61
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Ile His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 62
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 62
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Trp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 63
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 63
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro His Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 64
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 64
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Leu Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 65
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 65
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Ser Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 66
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 66
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ala Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Pro Asp Lys Met Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Pro Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Ser Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Leu Glu Pro Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Gln Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Thr Ala Leu Asn Asn Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Arg Ala
225 230 235 240
Gly Ala Lys Leu Ile Glu Asn Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Val Ala Ala Leu Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Glu His Arg Val Glu Gly Lys Tyr Phe Val Leu Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Ser Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Thr Glu Ala Ala Lys Lys Ile His Leu Ser Asn Leu Ser
355 360 365
Arg Ile Asp Gln Glu Thr Gln Lys Ile Phe Lys Ala Gly Lys Leu Met
370 375 380
Lys Pro Asp Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Tyr
385 390 395 400
Val Gln Phe Asp Cys Phe His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Ile Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Ala His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Asp
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Val Asn His Ile Thr Gly Ser
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Thr Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ala Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 67
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 67
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Ala His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 68
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 68
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Cys His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 69
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 69
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Asp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 70
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 70
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Glu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 71
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 71
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Gly His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 72
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 72
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys His His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 73
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 73
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Ile His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 74
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 74
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Lys His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 75
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 75
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Leu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 76
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 76
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Met His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 77
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 77
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Asn His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 78
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 78
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Gln His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 79
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 79
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Ser His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 80
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 80
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Pro His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 81
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 81
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Val His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 82
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 82
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Arg His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 83
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 83
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Thr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 84
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 84
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Trp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 85
<211> 550
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 85
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Tyr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
His His His His His His
545 550
<210> 86
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 86
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Ala His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 87
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 87
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Cys His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 88
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 88
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Asp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 89
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 89
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Glu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 90
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 90
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Gly His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 91
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 91
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys His His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 92
<211> 591
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 92
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val
50 55 60
Val Val Gly Ser Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala
65 70 75 80
Met Ala Gly Lys Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro
85 90 95
Arg Trp Glu Ile Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp
100 105 110
Phe Met Ala Pro Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr
115 120 125
Gly Pro Pro Asn Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn
130 135 140
Ser Gln Tyr Ile Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala
145 150 155 160
Ser Ala Trp Arg Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr
165 170 175
Gly Val Gly Arg Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr
180 185 190
Tyr Gln Arg Ala Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu
195 200 205
Glu Asp Leu Tyr Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu
210 215 220
Pro Leu Ser Phe Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr
225 230 235 240
Asp Pro Lys Phe His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg
245 250 255
Pro Tyr Asp Gly Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro
260 265 270
Ile Cys Pro Ile Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys
275 280 285
Ala Glu Gln Ala Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys
290 295 300
Leu Glu Thr Gly Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp
305 310 315 320
Lys Thr Gly Ala Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala
325 330 335
Ala Asn Gly Ile Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg
340 345 350
Asp Phe Pro Asn Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn
355 360 365
Leu Met Asp His Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys
370 375 380
Leu Trp Pro Gly Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe
385 390 395 400
Arg Asp Gly Pro Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu
405 410 415
Ser Asn Met Ser Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly
420 425 430
Gly Lys Leu Met Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg
435 440 445
Ser Ala Arg Phe Val Gln Phe Asp Cys Ile His Glu Ile Leu Pro Gln
450 455 460
Pro Glu Asn Arg Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly
465 470 475 480
Ile Pro Arg Pro Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg
485 490 495
Gly Ala Val His Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu
500 505 510
Gly Gly Thr Glu Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His
515 520 525
Ile Thr Gly Ala Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val
530 535 540
Asp Lys Asp Cys Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser
545 550 555 560
Ser Ser Thr Met Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile
565 570 575
Ala Ala Leu Ala Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
580 585 590
<210> 93
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 93
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Lys His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 94
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 94
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Leu His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 95
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 95
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Met His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 96
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 96
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Asn His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 97
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 97
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Gln His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 98
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 98
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Ser His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 99
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 99
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Pro His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 100
<211> 544
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 100
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Val His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
<210> 101
<211> 544
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 101
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Arg His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
<210> 102
<211> 544
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 102
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Thr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
<210> 103
<211> 544
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 103
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Trp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
<210> 104
<211> 544
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 104
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Tyr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val Gly Ser Gly Ser Gly
530 535 540
<210> 105
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 105
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Val His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 106
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 106
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Arg His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 107
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 107
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Thr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 108
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 108
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Trp His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535
<210> 109
<211> 539
<212> PRT
<213> 人工序列
<220>
<223> 重组序列
<400> 109
Met Ala Asp Thr Asp Thr Gln Lys Ala Asp Val Val Val Val Gly Ser
1 5 10 15
Gly Val Ala Gly Ala Ile Val Ala His Gln Leu Ala Met Ala Gly Lys
20 25 30
Ser Val Ile Leu Leu Glu Ala Gly Pro Arg Met Pro Arg Trp Glu Ile
35 40 45
Val Glu Arg Phe Arg Asn Gln Val Asp Lys Thr Asp Phe Met Ala Pro
50 55 60
Tyr Pro Ser Ser Ala Trp Ala Pro His Pro Glu Tyr Gly Pro Pro Asn
65 70 75 80
Asp Tyr Leu Ile Leu Lys Gly Glu His Lys Phe Asn Ser Gln Tyr Ile
85 90 95
Arg Ala Val Gly Gly Thr Thr Trp His Trp Ala Ala Ser Ala Trp Arg
100 105 110
Phe Ile Pro Asn Asp Phe Lys Met Lys Thr Val Tyr Gly Val Gly Arg
115 120 125
Asp Trp Pro Ile Gln Tyr Asp Asp Ile Glu His Tyr Tyr Gln Arg Ala
130 135 140
Glu Glu Glu Leu Gly Val Trp Gly Pro Gly Pro Glu Glu Asp Leu Tyr
145 150 155 160
Ser Pro Arg Lys Glu Pro Tyr Pro Met Pro Pro Leu Pro Leu Ser Phe
165 170 175
Asn Glu Gln Thr Ile Lys Ser Ala Leu Asn Gly Tyr Asp Pro Lys Phe
180 185 190
His Val Val Thr Glu Pro Val Ala Arg Asn Ser Arg Pro Tyr Asp Gly
195 200 205
Arg Pro Thr Cys Cys Gly Asn Asn Asn Cys Met Pro Ile Cys Pro Ile
210 215 220
Gly Ala Met Tyr Asn Gly Ile Val His Val Glu Lys Ala Glu Gln Ala
225 230 235 240
Gly Ala Lys Leu Ile Asp Ser Ala Val Val Tyr Lys Leu Glu Thr Gly
245 250 255
Pro Asp Lys Arg Ile Thr Ala Ala Val Tyr Lys Asp Lys Thr Gly Ala
260 265 270
Asp His Arg Val Glu Gly Lys Tyr Phe Val Ile Ala Ala Asn Gly Ile
275 280 285
Glu Thr Pro Lys Ile Leu Leu Met Ser Ala Asn Arg Asp Phe Pro Asn
290 295 300
Gly Val Ala Asn Ser Ser Asp Met Val Gly Arg Asn Leu Met Asp His
305 310 315 320
Pro Gly Thr Gly Val Ser Phe Tyr Ala Asn Glu Lys Leu Trp Pro Gly
325 330 335
Arg Gly Pro Gln Glu Met Thr Ser Leu Ile Gly Phe Arg Asp Gly Pro
340 345 350
Phe Arg Ala Asn Glu Ala Ala Lys Lys Ile His Leu Ser Asn Met Ser
355 360 365
Arg Ile Asn Gln Glu Thr Gln Lys Ile Phe Lys Gly Gly Lys Leu Met
370 375 380
Lys Pro Glu Glu Leu Asp Ala Gln Ile Arg Asp Arg Ser Ala Arg Phe
385 390 395 400
Val Gln Phe Asp Cys Tyr His Glu Ile Leu Pro Gln Pro Glu Asn Arg
405 410 415
Ile Val Pro Ser Lys Thr Ala Thr Asp Ala Val Gly Ile Pro Arg Pro
420 425 430
Glu Ile Thr Tyr Ala Ile Asp Asp Tyr Val Lys Arg Gly Ala Val His
435 440 445
Thr Arg Glu Val Tyr Ala Thr Ala Ala Lys Val Leu Gly Gly Thr Glu
450 455 460
Val Val Phe Asn Asp Glu Phe Ala Pro Asn Asn His Ile Thr Gly Ala
465 470 475 480
Thr Ile Met Gly Ala Asp Ala Arg Asp Ser Val Val Asp Lys Asp Cys
485 490 495
Arg Ala Phe Asp His Pro Asn Leu Phe Ile Ser Ser Ser Ser Thr Met
500 505 510
Pro Thr Val Gly Thr Val Asn Val Thr Leu Thr Ile Ala Ala Leu Ala
515 520 525
Leu Arg Met Ser Asp Thr Leu Lys Lys Glu Val
530 535

Claims (67)

1.一种包含以下序列的氨基酸的蛋白:
L(X)n=14X3(X)n=1X1(X)n=1E(X)n=4P(X)n=1NR(X)n=3S(X)n=4D(X)n=2G(X)n=7Y(X)n=4Y(X)n=32-34X2,其中每个X独立地表示任何天然存在的氨基酸残基,n表示由各自在该位置的圆括号表示的氨基酸残基的数目,其中:
a)X1选自由S,C,T,M,V,Y,N,P,L,G,Q,A,I,D,W,H或E组成的组,其中如果X1是L,H或V,则X3是D;和/或
b)X2选自由H,L,S或V组成的组。
2.根据权利要求1所述的蛋白,包含以下序列的氨基酸:(X)n=3-11D(X)n=1V(X)n=2G(X)n= 1G(X)n=2G(X)n=3A(X)n=5AG(X)n=2V(X)n=2LE(X)n=1GP(X)n=3R(X)n=3V(X)n=2FR(X)n=4K(X)n=5P(X)n=1P(X)n=4A(X)n=2P(X)n=5-6N(X)n=1YL(X)n=3G(X)n=7-9Y(X)n=1R(X)n=2GGT(X)n=1WHWA(X)n= 4R(X)n=2P(X)n=1D(X)n=6YG(X)n=2RDW(X)n=3Y(X)n=3E(X)n=2Y(X)n=2AE(X)n=3GV(X)n=1G(X)n=5- 9SPR(X)n=4P(X)n=23-25V(X)n=6RN(X)n=3YD(X)n=1RP(X)n=1C(X)n=1G(X)n=1NNCMP(X)n=1CP(X)n= 2A(X)n=1Y(X)n=1G(X)n=6A(X)n=2AG(X)n=6AVV(X)n=3E(X)n=8-9A(X)n=2Y(X)n=1D(X)n=5HRV(X)n= 5V(X)n=2A(X)n=3E(X)n=2K(X)n=4S(X)n=5P(X)n=1G(X)n=2N(X)n=5GRN(X)n=1MDH(X)n=4V(X)n=1F(X)n=6-7W(X)n=1GRGP(X)n=9RDG(X)n=2R(X)n=19T(X)n=12-14L(X)n=14X3(X)n=1X1(X)n=1E(X)n=4P(X)n=1NR(X)n=3S(X)n=4D(X)n=2G(X)n=7Y(X)n=4Y(X)n=32-34X2(X)n=2H(X)n=2G(X)n=3MG(X)n=5SV(X)n=1D(X)n=9NL(X)n=12T(X)n=1N(X)n=1TLT(X)n=2AL(X)n=1L(X)n=3D(X)n=2-6,其中X表示任何天然存在的氨基酸残基,n表示由各自在该位置的圆括号表示的氨基酸残基的数目,其中:
a)X1选自由S,C,T,M,V,Y,N,P,L,G,Q,A,I,D,W,H或E组成的组,其中如果X1是L,H或V,则X3是D;和/或
b)X2选自由H,L,S或V组成的组。
3.一种包含SEQ ID NO:38所示序列的氨基酸的蛋白,不同之处在于:
a)406位置的氨基酸是除F以外的氨基酸;和/或
b)474位置的氨基酸是除N以外的氨基酸。
4.根据权利要求3所述的蛋白,其中所述406位置的氨基酸选自由S,C,T,M,V,Y,N,P,L,G,Q,A,I,D,W,H和E组成的组。
5.根据权利要求3或4所述的蛋白,其中所述474位置的氨基酸选自由H,L,S和V组成的组。
6.根据权利要求3-4中任一项所述的蛋白,其中
a)所述406位置的氨基酸是除F以外的氨基酸;并且
b)所述474位置的氨基酸为N。
7.根据权利要求3或5中任一项所述的蛋白,其中
a)所述406位置的氨基酸为F;并且
b)所述474位置的氨基酸是除N以外的氨基酸。
8.根据权利要求3-5中任一项所述的蛋白,其中
a)所述406位置的氨基酸是除F以外的氨基酸;并且
b)所述474位置氨基酸是除N以外的氨基酸。
9.根据权利要求1-8中任一项所述的蛋白,其中所述蛋白与包含SEQ ID NO:38的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少10%的生化活性。
10.根据权利要求1-8中任一项所述的蛋白,其中所述蛋白与包含SEQ ID NO:38的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少40%的选择性。
11.根据权利要求1-8中任一项所述的蛋白,其中所述蛋白与包含SEQ ID NO:38的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少20%的线性。
12.根据权利要求3所述的蛋白,包含SEQ ID NO:46所述的序列的氨基酸。
13.根据权利要求3所述的蛋白,包含SEQ ID NO:47所述的序列的氨基酸。
14.根据权利要求3所述的蛋白,包含SEQ ID NO:48所述的序列的氨基酸。
15.根据权利要求3所述的蛋白,包含SEQ ID NO:49所述的序列的氨基酸。
16.根据权利要求3所述的蛋白,包含SEQ ID NO:50所述的序列的氨基酸。
17.根据权利要求3所述的蛋白,包含SEQ ID NO:51所述的序列的氨基酸。
18.根据权利要求3所述的蛋白,包含SEQ ID NO:52所述的序列的氨基酸。
19.根据权利要求3所述的蛋白,包含SEQ ID NO:53所述的序列的氨基酸。
20.根据权利要求3所述的蛋白,包含SEQ ID NO:54所述的序列的氨基酸。
21.根据权利要求3所述的蛋白,包含SEQ ID NO:55所述的序列的氨基酸。
22.根据权利要求3所述的蛋白,包含SEQ ID NO:56所述的序列的氨基酸。
23.根据权利要求3所述的蛋白,包含SEQ ID NO:57所述的序列的氨基酸。
24.根据权利要求3所述的蛋白,包含SEQ ID NO:58所述的序列的氨基酸。
25.根据权利要求3所述的蛋白,包含SEQ ID NO:59所述的序列的氨基酸。
26.根据权利要求3所述的蛋白,包含SEQ ID NO:60所述的序列的氨基酸。
27.根据权利要求3所述的蛋白,包含SEQ ID NO:61所述的序列的氨基酸。
28.根据权利要求3所述的蛋白,包含SEQ ID NO:62所述的序列的氨基酸。
29.根据权利要求3所述的蛋白,包含SEQ ID NO:63所述的序列的氨基酸。
30.根据权利要求3所述的蛋白,包含SEQ ID NO:64所述的序列的氨基酸。
31.根据权利要求3所述的蛋白,包含SEQ ID NO:65所述的序列的氨基酸。
32.根据权利要求3所述的蛋白,包含SEQ ID NO:66所述的序列的氨基酸。
33.一种包含SEQ ID NO:39所述序列的氨基酸的蛋白,不同之处在于:
a)406位置的氨基酸是除F以外的氨基酸;和/或
b)474位置的氨基酸是除N以外的氨基酸。
34.根据权利要求34所述的蛋白,其中所述406位置的氨基酸选自由S,C,T,M,V,Y,N,P,L,G,Q,A,I,D,W,H和E组成的组。
35.根据权利要求34或35所述的蛋白,其中所述474位置的氨基酸选自由H,L,S和V组成的组。
36.根据权利要求34-35中任一项所述的蛋白,其中
a)所述406位置的氨基酸是除F以外的氨基酸;并且
b)所述474位置的氨基酸为N。
37.根据权利要求34或36中任一项所述的蛋白,其中
a)所述406位置的氨基酸为F;并且
b)所述474位置的氨基酸是除N以外的氨基酸。
38.根据权利要求34-36中任一项所述的蛋白,其中
a)所述406位置的氨基酸是除F以外的氨基酸;并且
b)所述474位置的氨基酸是除N以外的氨基酸。
39.根据权利要求34-39中任一项所述的蛋白,其中所述蛋白与包含SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少10%的生化活性。
40.根据权利要求34-39中任一项所述的蛋白,其中所述蛋白与包含SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少40%的选择性。
41.根据权利要求34-39中任一项所述的蛋白,其中所述蛋白与包含SEQ ID NO:39的氨基酸序列的FAD-GDHα野生型蛋白相比表现出增加至少20%的线性。
42.根据权利要求34所述的蛋白,包含SEQ ID NO:86所述的序列的氨基酸。
43.根据权利要求34所述的蛋白,包含SEQ ID NO:87所述的序列的氨基酸。
44.根据权利要求34所述的蛋白,包含SEQ ID NO:88所述的序列的氨基酸。
45.根据权利要求34所述的蛋白,包含SEQ ID NO:89所述的序列的氨基酸。
46.根据权利要求34所述的蛋白,包含SEQ ID NO:90所述的序列的氨基酸。
47.根据权利要求34所述的蛋白,包含SEQ ID NO:91所述的序列的氨基酸。
48.根据权利要求34所述的蛋白,包含SEQ ID NO:92所述的序列的氨基酸。
49.根据权利要求34所述的蛋白,包含SEQ ID NO:93所述的序列的氨基酸。
50.根据权利要求34所述的蛋白,包含SEQ ID NO:94所述的序列的氨基酸。
51.根据权利要求34所述的蛋白,包含SEQ ID NO:95所述的序列的氨基酸。
52.根据权利要求34所述的蛋白,包含SEQ ID NO:96所述的序列的氨基酸。
53.根据权利要求34所述的蛋白,包含SEQ ID NO:97所述的序列的氨基酸。
54.根据权利要求34所述的蛋白,包含SEQ ID NO:98所述的序列的氨基酸。
55.根据权利要求34所述的蛋白,包含SEQ ID NO:99所述的序列的氨基酸。
56.根据权利要求34所述的蛋白,包含SEQ ID NO:100所述的序列的氨基酸。
57.根据权利要求34所述的蛋白,包含SEQ ID NO:101所述的序列的氨基酸。
58.根据权利要求34所述的蛋白,包含SEQ ID NO:102所述的序列的氨基酸。
59.根据权利要求34所述的蛋白,包含SEQ ID NO:103所述的序列的氨基酸。
60.根据权利要求34所述的蛋白,包含SEQ ID NO:104所述的序列的氨基酸。
61.一种葡萄糖传感器,包含根据权利要求1-61中任一项所述的蛋白。
62.一种组合物,包含载体和固定在所述载体上的根据权利要求1-61中任一项所述的蛋白。
63.根据权利要求63所述的组合物,处于干燥状态或固体状态。
64.根据权利要求1-61中任一项所述的蛋白,被固定至葡萄糖传感器电极的导电部件。
65.一种编码根据权利要求1-61中任一项所述的蛋白的DNA序列。
66.一种宿主细胞,包含根据权利要求1-61中任一项所述的蛋白或包含编码所述蛋白的DNA。
67.一种生产蛋白的方法,包括在有利于生产所述蛋白的条件下培养根据权利要求67所述的宿主细胞,并且回收所述蛋白。
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108368489A (zh) * 2015-07-23 2018-08-03 智慧酶生物医药有限公司 用于测量血液葡萄糖水平的组合物和方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040023330A1 (en) * 2000-10-31 2004-02-05 Koji Sode Novel glucose dehydrogenase and process for producing the dehydrogenase
CN1973036A (zh) * 2004-04-23 2007-05-30 爱科来株式会社 突变的葡萄糖脱氢酶
CN101717777A (zh) * 2009-08-24 2010-06-02 浙江大学 耐碱性葡萄糖脱氢酶基因及其编码的多肽和制备方法
CN102453702A (zh) * 2010-10-27 2012-05-16 爱科来株式会社 变异葡萄糖脱氢酶
CN102559624A (zh) * 2012-03-05 2012-07-11 浙江德清汇宁生物科技有限公司 一种吡咯喹啉醌依赖型葡萄糖脱氢酶的热稳定性突变体及其高通量筛选方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040023330A1 (en) * 2000-10-31 2004-02-05 Koji Sode Novel glucose dehydrogenase and process for producing the dehydrogenase
CN1973036A (zh) * 2004-04-23 2007-05-30 爱科来株式会社 突变的葡萄糖脱氢酶
CN101717777A (zh) * 2009-08-24 2010-06-02 浙江大学 耐碱性葡萄糖脱氢酶基因及其编码的多肽和制备方法
CN102453702A (zh) * 2010-10-27 2012-05-16 爱科来株式会社 变异葡萄糖脱氢酶
CN102559624A (zh) * 2012-03-05 2012-07-11 浙江德清汇宁生物科技有限公司 一种吡咯喹啉醌依赖型葡萄糖脱氢酶的热稳定性突变体及其高通量筛选方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108368489A (zh) * 2015-07-23 2018-08-03 智慧酶生物医药有限公司 用于测量血液葡萄糖水平的组合物和方法

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