CN1768137A - 枯草杆菌酶 - Google Patents
枯草杆菌酶 Download PDFInfo
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- CN1768137A CN1768137A CNA2004800087211A CN200480008721A CN1768137A CN 1768137 A CN1768137 A CN 1768137A CN A2004800087211 A CNA2004800087211 A CN A2004800087211A CN 200480008721 A CN200480008721 A CN 200480008721A CN 1768137 A CN1768137 A CN 1768137A
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Abstract
本发明涉及产生亲本TY145枯草杆菌酶变体及亲本BPN’枯草杆菌酶变体的方法,并涉及与亲本TY145/BPN’枯草杆菌酶相比具有改变的特性的TY145和BPN’变体。
Description
发明领域
本发明涉及TY145枯草杆菌酶(subtilase)和BPN’枯草杆菌酶的变体及构建这些具有改变特性的变体的方法,所述特性包括如稳定性(例如热稳定性或储藏稳定性)、Ca2+依赖性、pH依赖的活性。
发明背景
酶已在在洗涤剂工业中作为洗涤制剂的一部分使用了30年以上。从商业观点看蛋白酶是这些制剂中最相关的酶,但也经常使用其他酶包括脂肪酶、淀粉酶、纤维素酶、半纤维素酶或酶混合物。
为改进蛋白酶的成本和/或性能,正在寻找具有改变特性的蛋白酶,这些特性如:更高的低温活性、更高的热稳定性、在给定pH下更高的比活性、改变的Ca2+依赖性、在其他洗涤剂成份(例如漂白剂、表面活性剂等)存在下更高的稳定性等。
寻找具有改变特性的蛋白酶包括发现天然存在的蛋白酶(即所谓野生型蛋白酶)和改造已熟知的蛋白酶(如通过对编码所述蛋白酶的核酸序列的基因操作)。对蛋白质三维结构和功能之间关系的认识提高了评估改变蛋白质的哪一区域来影响蛋白质特定性状的能力。
经常在洗涤剂中使用的一个蛋白酶家族是枯草杆菌酶。Siezen RJ和Leunissen(JAM,1997,Protein Science,6,501-523.)先前把该家族进一步分为6个亚组。其中一个亚组为枯草菌素家族,包括枯草杆菌酶如BPN’、枯草菌素309(SAVINASE_、NOVOZYMES A/S)、枯草菌素Carlsberg(ALCALASE_、NOVOZYMES A/S)、枯草菌素S41(来源于嗜冷南极芽孢杆菌(psychrophilic Antarctic Bacillus)TA41的枯草杆菌酶,Davail S等.1994,The Journal of Biological Chemistry,269(26),99.17448-17453)、枯草菌素S39(来源于嗜冷南极芽孢杆菌TA39的枯草杆菌酶,Narinx E等.1997,Protein Engineering,10(11),1271-1279页)和TY145(来源于芽孢杆菌属(Bacillus sp)的枯草杆菌酶.TY145,描述于WO 92/17577的NCIMB 40339)。
然而,尽管属于枯草杆菌酶中枯草菌素亚组的枯草杆菌酶间有序列同源性,由于结构差异,基于一种枯草杆菌酶的三维结构模拟另一枯草杆菌酶的三维结构模型可能导致不正确的三维结构。
本发明的发明人阐明了TY145枯草杆菌酶的三维结构,并发现它与同属枯草杆菌酶中枯草菌素亚组的BPN’的三维结构之间存在若干差别。结构上令人吃惊的差异使得以TY145的结构作为基础有利于TY145样枯草菌素的同源建模,而这反之又可以进而提高通过蛋白质工程获得需要的功能性改变的能力。
已有两项研究使用蛋白质工程改变TY145样枯草菌素的功能:Miyazaki K等.2000,J Mol Biol,297,1015-1026页公开了通过定向进化的方法提高嗜冷蛋白酶枯草菌素S41的热稳定性和活性。
Wintrode TL等.2000,Journal of Biological Chemistry,275(41),31635-31640页公开了通过定向进化的方法将球形芽孢杆菌(Bacillussphaericus)SSII来源的嗜温枯草菌素样蛋白酶转化为其嗜冷负体。Wintrode等人基于SSII枯草杆菌酶与枯草菌素Carlsberg、Savinase、BPN′和Thermitase间的同源性建立了它的三维结构模型。然而,根据本发明SSII枯草杆菌酶属于TY145样枯草杆菌酶这一新组,因此基于BPN’样枯草杆菌酶3D结构的SSII建模很可能给出不准确的结果。
TY145和BPN’三维结构的差别被最近发表的球形芽孢杆菌来源的枯草杆菌酶“球形酶”的三维结构(PDB NO:1EA7,Protein Data Bank)所证实。该枯草杆菌酶的总体结构和许多细节与枯草杆菌酶TY145的结构高度同源。
发明概述
基于枯草杆菌酶TY145和BPN’的三维结构,发明者修饰了枯草杆菌酶的氨基酸序列以获得具有改进特性的变体。变体具有改变的特性,如更高的低温活性、更高的热稳定性、在给定pH下更高的比活性、不同的Ca2+依赖性、在其他洗涤剂成份(例如漂白剂、表面活性剂等)存在下更高的稳定性等。
因此,本发明的目的在于提供构建具有改变特性的枯草杆菌酶的方法,尤其是提供构建具有上述改变特性的枯草杆菌酶的方法。
因此,在最广义的方面,本发明涉及构建亲本枯草杆菌酶变体的方法,其中变体与所述亲本枯草杆菌酶相比具有至少一项改变的特性,其方法包括:
i)在评估结构因素的基础上分析枯草杆菌酶的三维结构,以鉴定出该枯草杆菌酶中与改变所述特性相关的至少一个氨基酸残基或至少一个结构区域;
ii)构建枯草杆菌酶的变体,其与亲本枯草杆菌酶相比修饰了i)中鉴定的氨基酸残基或结构部分以改变所述特性;并
iii)测试产生的枯草杆菌酶变体的所述特性。
尽管下文已有所说明,在某一区域和/或位置对亲本枯草杆菌酶的修饰是为了给产生的枯草杆菌酶变体以特定的影响,应该注意在任何这样的区域和/或位点对亲本枯草杆菌酶进行修饰可能还会引起前述的任何其他效果。例如,任何被提到对如提高热稳定性有特殊影响的区域和/或位点,也可能引起例如在较低pH下更高的活性、改变最佳pH、或更高的比活性(如更高的肽酶活性)。
本发明还有的方面涉及枯草杆菌酶的变体、编码这类变体的DNA和制备变体的方法。本发明还有的方面还涉及变体在多种工业目的中的用途,特别是作为洗涤剂组合物中的添加物。本发明的其他方面在下面的描述和附加的权利要求书中是显而易见的。
附录简述
附录1显示解出的TY145枯草杆菌酶晶体三维结构的结构坐标。
附图简述
图一显示Ty145、TA39、TA41、球形芽孢杆菌和Savinase来源的枯草杆菌酶3D序列的多重比对。
图二显示枯草菌素BPN’和Savinase的氨基酸序列比对,以定义Savinase的BPN’编号。
图三显示TY145枯草杆菌酶(亮)和BPN’结构(暗)的叠加,圆球表示离子结合位点。TY145的离子结合位点标记为亮色而BPN’的离子结合位点标记为暗色。
定义
在更详细地讨论本发明之前,首先定义以下的术语和约定。
对氨基酸和核酸命名法的详细描述,我们参照WO 00/71691的第5页,此处引用作为参考。对于通过基因操作向多肽中引入的修饰,其命名法的说明见WO 00/71691的7-12页,此处引用作为参考。
术语“枯草杆菌酶”指根据Siezen等,《Protein Engng.4》(1991)719-737和Siezen等,《Protein Science 6》(1997)501-523的丝氨酸蛋白酶亚组。丝氨酸蛋白酶或丝氨酸肽酶是蛋白酶的一个亚组,其特征在于活性位点有一个丝氨酸,与底物形成共价加合物。另外枯草杆菌酶(和丝氨酸蛋白酶)特征还在于除了丝氨酸外有两个活性位点氨基酸残基,即组氨酸和天冬氨酸残基。
枯草杆菌酶是通过对170多个先前称为枯草菌素样蛋白酶的丝氨酸蛋白酶的氨基酸序列进行同源性分析而定义的。枯草杆菌酶可以分为六个亚组,即枯草菌素家族、Thermitase家族、蛋白酶K家族、Lantibiotic肽酶家族、Kexin家族和Pyrolysin家族。
枯草菌素家族(EC 3.4.21.62)可被进一步分为三个亚组,即I-S1(“真”枯草菌素)、I-S2(高度碱性蛋白酶)和细胞内枯草菌素。酶的定义和分组可以不同或改变,然而,在本发明的上下文中,上述将枯草菌素划分为亚类或亚组的分类法应按照Siezen等,《Protein Engng.4》(1991)719-737和Siezen等,《Protein Science 6》(1997)501-523的描述来理解。
术语“亲本”在本发明的上下文中应理解为被修饰以产生蛋白质变体的蛋白质。亲本蛋白质可以是天然存在(野生型)的多肽或是通过任何适当手段制备的天然多肽的变体。例如,亲本蛋白质可以是对天然存在蛋白质进行修饰得到的天然存在蛋白质的变体,其中修饰可以是替换、化学修饰、缺失或截短一个或多个氨基酸残基,或在氨基酸序列中添加或插入一个或多个氨基酸残基。因此,术语“亲本枯草杆菌酶”指被修饰以产生枯草杆菌酶变体的枯草杆菌酶。
术语“变体”在本发明的上下文中应理解为与亲本蛋白质比较在一个或多个氨基酸残基上被修饰的蛋白质。
术语“修饰”或“修饰的”在本发明的上下文中应理解为包括对蛋白质的化学修饰和对编码蛋白质的DNA的基因操作。修饰可以是氨基酸侧链的取代、目标氨基酸处的替换、缺失和/或插入。因此术语“修饰的蛋白质”(如“修饰的枯草杆菌酶”)应理解为与亲本蛋白质(如枯草杆菌酶)相比含有修饰的蛋白质。
术语“TY145枯草杆菌酶”或“TY145样枯草杆菌酶”在本发明的上下文中应理解为根据Siezen等,《Protein Science 6》(1997)501-523属于枯草菌素组,并与TY145,SEQ ID NO:1具有至少63%的同源性的枯草杆菌酶。在本发明的上下文中TY145枯草杆菌酶有三个离子结合位点。
术语“BPN’枯草杆菌酶”或“BPN’样枯草杆菌酶”在本发明的上下文中应理解为根据Siezen等,《Protein Science 6》(1997)501-523属于枯草菌素组,并与BPN’,SEQ ID NO:5具有至少61%的同源性的枯草杆菌酶。这样的BPN’样枯草杆菌酶为例如Savinase。在本发明的上下文中BPN’枯草杆菌酶有两个、三个或五个离子结合位点。在本发明的上下文中BPN’样枯草杆菌酶可以属于枯草菌素的I-S分支,即I-S1分支,“真”枯草菌素或I-S2,高度碱性枯草菌素(Siezen等,《Protein Engng.4》(1991)719-737)。
在本发明的上下文中“同源”或“与……同源”应理解为其常规含义,并且两氨基酸序列间的“同源性”应使用威斯康辛大学遗传学计算组(University of Wisconsin Genetic Computer Group)(UWGCG)的软件包中的GAP程序所定义的“相似性”来测定,对于比对参数、比较矩阵、缺口和缺口罚分均使用默认设置。GAP罚分的默认值,例如缺口创建罚分为3.0而缺口延伸罚分为0.1(Program Manual for theWisconsin Package,第8版,1994年8月,Genetics Computer Group,575 Science Drive,Madison,Wisconsin,USA 53711)。该方法在S.B.Needleman和C.D.Wunsch,Journal of Molecular Biology,48,443-445(1970)中也有描述。同一性可由相同的计算得到。两氨基酸序列间的同源性还可以用由UWGCG软件包9.1版的GAP程序计算出的“同一性”或“相似性”测定,使用默认序列比对参数、比较矩阵、缺口和缺口罚分,也可应用下列参数实施:缺口创建罚分=8而缺口延伸罚分=8,所有其他参数保持为其默认值。程序的输出除了氨基酸序列比对外还有“同一性百分比”和“相似性”的计算结果。用UWGCG软件包9.1版计算出的数字与8.0版略有差别。
术语“位置”在本发明的上下文中应理解为在蛋白质或多肽中从N-末端开始计算的氨基酸编号。本发明中使用的关于不同枯草杆菌酶的位置编号取决于该枯草杆菌酶属于哪一亚组。
已知的四种属于TY145亚组的枯草杆菌酶,即从TY145、TA39、TA41、和球形杆菌获得的枯草杆菌酶分别按照SEQ ID NO:1、2、3、和4编号。
同样的,其他属于TY145亚组的枯草杆菌酶各自按照其自身序列编号。然而为了确定这些其他枯草杆菌酶的同源位置,将其按照前述GAP程序与SEQ ID NO:1、2、3和4分别进行比对。然后根据与SEQID NO:1、2、3、和4同源性最高确定同源位置。
另外,属于TY145亚组的枯草杆菌酶可以参照TY145枯草杆菌酶(SEQ ID NO:1)的位置来编号。
属于BPN’亚组的枯草杆菌酶参照来自解淀粉芽孢杆菌(B.amyloliquefaciens)的枯草菌素Novo(BPN’)(SEQ ID NO:5)的位置。
发明详述
尽管上文所述枯草杆菌酶有很高的同源性,本发明的发明人通过X射线衍射晶体分析法阐明了TY145,SEQ ID NO:1的三维结构并发现TY145和BPN’的三维结构之间存在若干重要差异。本发明的发明人进一步比较了具有代表性数目的属于枯草菌素亚组的枯草杆菌酶的序列同源性。如以下表一同源性矩阵所示。
No. | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 |
1 | 100 | 93 | 76 | 51 | 50 | 51 | 55 | 52 | 54 | 58 | 58 | 59 | 57 | 60 | 60 |
2 | 100 | 75 | 52 | 52 | 52 | 56 | 53 | 55 | 58 | 58 | 61 | 58 | 62 | 61 | |
3 | 100 | 60 | 60 | 60 | 58 | 60 | 62 | 58 | 57 | 59 | 59 | 62 | 59 | ||
4 | 100 | 99 | 99 | 97 | 91 | 76 | 63 | 69 | 74 | 66 | 74 | 74 | |||
5 | 100 | 99 | 97 | 90 | 76 | 69 | 74 | 66 | 74 | 74 | 56 | ||||
6 | 100 | 98 | 91 | 77 | 63 | 69 | 74 | 66 | 74 | 74 | |||||
7 | 100 | 88 | 79 | 69 | 67 | 74 | 74 | 74 | 74 | ||||||
8 | 100 | 77 | 66 | 71 | 74 | 67 | 74 | 74 | |||||||
9 | 100 | 64 | 69 | 74 | 67 | 73 | 73 | ||||||||
10 | 1OO | 99 | 76 | 72 | 76 | 76 | |||||||||
11 | 100 | 76 | 76 | 76 | 76 | ||||||||||
12 | 100 | 99 | 99 | 99 | |||||||||||
13 | 100 | 99 | 99 | ||||||||||||
14 | l00 | 98 | |||||||||||||
15 | 100 |
表一图例
TY145样枯草杆菌酶
1:q45681;枯草芽孢杆菌(B.subtilis)(BSTA41)来源的枯草杆菌酶。
2:p28842;南极芽孢杆菌菌株(BSTA39)来源的嗜冷枯草菌素。
3:abb77095;芽孢杆菌(TY145)来源的枯草杆菌酶。
BPN’样枯草杆菌酶,I-S1:
4:p00783;枯草芽孢杆菌var.amylosacchariticus(BSAMY)来源的枯草杆菌酶。
5:p29142;嗜热脂肪芽孢杆菌(Bacillus stearothermophilus)(BSSJ)来源的枯草杆菌酶。
6:p35835;枯草芽孢杆菌var.natto.(BSNAT)来源的枯草杆菌酶。
7:p07518;短小芽孢杆菌(Bacillus pumilus)(B.mesentericus)(BPMES)来源的枯草杆菌酶。
8:p00782;解淀粉芽孢杆菌(Bacillus amyloliquefaciens)(BPN’)来源的枯草杆菌酶。
9:p00780;地衣芽孢杆菌(Bacillus licheniformis)(BLSCAR)来源的枯草杆菌酶。
BPN’样枯草杆菌酶,I-S2:
10:p41363;耐盐芽孢杆菌(Bacillus halodurans)(BHSAH)来源的枯草杆菌酶。
11:aaw62222;迟缓芽孢杆菌(Bacillus lentus)(BLS147)来源的枯草杆菌酶。
12:p29600;迟缓芽孢杆菌(BLSAVI,BLS309)来源的枯草杆菌酶。
13:p27693;嗜碱芽胞杆菌(Bacillus alcalophilus)(BAALKP)来源的枯草杆菌酶。
14:q99405;枯草杆菌菌株KSM-K16(BSKSMK)来源的枯草杆菌酶。
15:p29599;迟缓芽孢杆菌(BLSUBL)来源的枯草杆菌酶。
基于3D结构和蛋白序列的比较,本发明的发明人在所附的TY1453D结构和BPN’3D结构的3D结构比较基础上发现,TY145枯草杆菌酶亚组与BPN’枯草杆菌酶不同,TY145和BPN’的序列同源性也指出了这一点。
TY145枯草杆菌酶
如前文所述,枯草杆菌酶TY145在本发明上下文中应理解为与SEQID NO:1有至少63%同源性的枯草杆菌酶。具体而言,所述TY145枯草杆菌酹可以与TY145即SEQ ID NO:1有至少65%,例如至少70%、至少80%、至少83%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%的同源性。
在本发明的第一个实施方案中,适合本文所述目的的TY145枯草杆菌酶可以是与TY145的三维结构同源的枯草杆菌酶,即与附录1中结构坐标定义的三维结构同源。
如本领域技术人员所熟知,蛋白质或其部分的结构坐标集就是在三维空间定义了形状的点的相对集合,完全不同的坐标集可能定义相同或者相似的形状。此外,单个坐标的轻微改变可能对总体形状没有或几乎没有影响。
这些坐标的改变可能是由于结构坐标的数学处理而产生。例如,可以通过结构坐标的结晶学变换、结构坐标的分段、结构坐标集的整体添加或消减、结构坐标的翻转或任何前述的组合来处理附录1(TY145结构)的结构坐标。另外,所述改变也可能是由于一级氨基酸序列的不同。
如果这些变体与附录1的结构坐标相比在可接受的标准差范围内,则该三维结构在本发明上下文中应理解为与附录1的结构同源。标准差一般可以通过例如保守的主链残基的均方根偏差来衡量,其中术语“均方根偏差”(RMS)意为偏离平均值的平方的算术平均值的平方根。
如本领域技术人员所熟知,在一组具有同源结构的蛋白质中也可能在其结构的某些部分或区域(例如环)存在三维结构上的不同,所述部分或区域并非(或至少不仅仅)对结构的功能结构域具有次重要性,而是可能导致所述结构中保守残基主链原子间巨大的均方根偏差。
因此,众所周知结构坐标集是与结晶蛋白质唯一对应的。其他三维结构,即使是同源结构甚至是以不同方式结晶的同一蛋白质都不具有完全相同的坐标集。坐标中存在着自然波动。可以发现总体结构和原子间的关系是相似的。这种相似性可以就一个结构中的每个原子与另一结构中每个“同源的”原子间的均方根偏差来讨论。然而,只有完全一致的蛋白质具有完全相同的原子数。所以,相似性低于100%的蛋白质通常具有不同的原子数,因此无法计算所有原子的均方根偏差,而只能计算那些认为是“同源”的。因此基于座标的相似性的精确描述对于同源蛋白质来说难以说明和计算。关于本发明,不同枯草杆菌酶3D结构间的相似性可通过同源结构元件的含量和/或氨基酸或DNA序列的相似性来说明。对于没有缺失或插入的序列,可以计算钙原子的RMS。
TY145样枯草杆菌酶的实例包括来自南极芽孢杆菌TA41的嗜冷枯草菌素S41,本文也称为TA41枯草杆菌酶(Davail S等,1994,J.Biol.Chem.,269,17448-17453),以及来自南极芽孢杆菌TA39的嗜冷枯草菌素S39,本文也称为TA39枯草杆菌酶(Narinx E等,1997,ProteinEngineering,10(11),1271-1279)。最近一种与TY145枯草菌素同源的枯草菌素的三维结构公布于Protein Data Bank(登录号No:1EA7)。这种球形芽孢杆菌的“球形”枯草杆菌酶的总体结构和许多细节与TY145枯草杆菌酶的结构高度同源。然而该球形酶结构显示出多至5个离子结合位点。相似结构的离子结合位点的数目可能根据结晶使用的介质而变化。因此看来球形芽孢杆菌“球形酶”额外的两个离子结合位点是含钙的结晶介质所致。
因此,本发明一个优选的实施方案为亲本枯草杆菌酶或枯草杆菌酶变体,其与SEQ ID NO:1序列具有至少63%的同源性,优选与SEQ IDNO:1序列具有至少65%、至少70%、至少74%、至少80%、至少83%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%的同源性,并任选地所述枯草杆菌酶还包含如下结构特征:
a)具有7条链的扭曲的β片层,
b)6个α螺旋
c)至少3个离子结合位点,和
其中不存在BPN’样枯草杆菌酶的强离子结合位点,且TY145枯草杆菌酶、TA39枯草杆菌酶、TA41枯草杆菌酶以及球形芽孢杆菌“球形酶”除外。
本发明TY145枯草杆菌酶由分离的核酸序列编码,其核酸序列与SEQ ID NO:20中给出的核酸序列具有至少45%、至少50%、至少55%、至少60%、至少65%、至少70%、至少75%、至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%,、至少95%、至少96%、至少97%、至少98%或至少99%的同源性。
另外编码本发明TY145枯草杆菌酶的分离的核酸序列与SEQ IDNO:20中给出的核酸序列的互补链优选在低严格条件下杂交,至少在中度严格条件下,至少在中/高严格条件下,至少在高严格条件下,至少在极高严格条件下杂交。
鉴定核苷酸探针与同源DNA或RNA序列在低、中或高严格条件下杂交的适当的实验条件包括将含有用于杂交的DNA片段或RNA的滤器在5×SSC(氯化钠/柠檬酸钠,Sambrook等,1989)中预浸泡10分钟、在含5×SSC、5×Denhardt’s液(Sambrook等,1989)、0.5%SDS及100μg/ml变性的超声处理鲑精DNA(Sambrook等,1989)的溶液中预杂交滤器,接着在含有浓度为10ng/ml随机引发的(Feinberg,A.P.和Vogelstein.B.(1983)Anal.Biochem.132:6-13)、32P-dCTP标记(比活性>1×109cpm/μg)探针的相同溶液中在45℃下杂交12小时,然后以2×SSC、0.5%SDS在至少*55℃(低严格)下洗涤两遍30分钟,优选至少60℃(中度严格),更优选至少65℃(中/高严格),甚至更优选至少70℃(高严格),甚至更优选至少75℃(极高严格)。
BPN’枯草杆菌酶
如前述,本发明上下文中的BPN’枯草杆菌酶应理解为与SEQ IDNO:5具有至少61%同源性的枯草杆菌酶。特别是所述BPN’枯草杆菌酶可与BPN’即SEQ ID NO:5具有至少70%的同源性,如具有至少75%、至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%,或至少99%的同源性。
本发明的一个实施方案中,适合本文所述目的的BPN’枯草杆菌酶可以是与如PDB Nos.1SBT和1GNS(Proteim Data Bank)中给出的结构坐标所定义的BPN’三维结构同源的枯草杆菌酶,或是与在ProteinData Bank中可查询的其他几个BPN’结构之一同源的枯草杆菌酶。同源结构间的变化可由于前述若干原因而产生。因此本发明上下文中的BPN’枯草杆菌酶应理解为具有属于前述BPN’枯草杆菌酶结构特征的任何枯草杆菌酶,另外,该枯草杆菌酶优选不含有在前述BPN’枯草杆菌酶中不存在的其他结构特征。另外,本发明BPN’枯草杆菌酶应与SEQID NO:5具有必要的相似性百分率。
BPN’样枯草杆菌酶的实例除其他以外,还包括枯草菌素309(PDBNO:1SVN SAVINASE_,NOVOZYMES A/S)和枯草菌素Carlsberg(ALCALASE_,NOVOZYMES A/S)等等。
R.J.Siezen和J.A.M Leunissen(Protein science,Vol.6(3),501-523页,1997)502页中图1描述了枯草杆菌酶的结构。枯草杆菌酶包含6-8个螺旋、11条链,其中7条位于扭曲的β片层的中心。提到了两个离子结合位点,其中一个为所谓“弱”钙结合位点。后来发现在某些结构中(枯草菌素DY PDB no.1BH6,1998),当结晶介质中钙浓度低时,该钙结合位点表现为Na(钠)结合位点。因此,我们以下称为离子结合位点而不是钙结合位点。
本发明BPN’枯草杆菌酶由分离的核酸序列编码,其核酸序列与SEQ ID NO:21所示的核酸序列有至少45%、至少50%、至少55%、至少60%、至少65%、至少70%、至少75%、至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%或至少99%的同源性。
另外编码本发明BPN’枯草杆菌酶的分离的核酸序列与SEQ IDNO:21中给出核酸序列的互补链优选在低严格条件下杂交,但至少在中度严格条件下、至少在中/高严格条件下、至少在高严格条件下、至少在极高严格条件下杂交。
TY145枯草杆菌酶的三维结构
TY145枯草杆菌酶用来说明构成本发明基础的三维结构。
按照x射线结晶学方法的原则(如《X-Ray StructureDetermination》,Stout,G.K.和Jensen,L.H.,John Wiley & Sons,Inc.NY,1989中所给出的原则)解出了TY145结构。
解出的TY145晶体结构的结构坐标以如附录1中列出的标准PDB格式(Protein Data Bank,Brookhaven National Laboratory,Brookhaven,CT)给出。应该理解附录1构成了本申请的一部分。在附录1上下文中使用了如下缩写:CA指c-α(碳原子)或钙离子(然而为了避免误解我们在本说明书中使用全名“c-α原子”和“钙”或“离子”)。氨基酸残基以标准三字母代码给出。附带的结构坐标包含蛋白酶结构、抑制剂结构CI2以及水分子。蛋白酶坐标的链标识称为A,而CI2抑制剂称为B,钙离子称为C,水为W。下文提及残基的位置参照SEQ ID NO:1公开的TY145序列。
TY145结构显示出与在S8枯草菌素家族中发现的相同的“总体”折叠方式。其结构包括7条链按照S2、S3、S1、S4、S5、S6、S7顺次排列形成的扭曲β片层。结构中有6个α螺旋,其编号H1包括残基9-15,H2包括残基72-81,H3包括残基114-131,H4包括残基148-158,H5包括残基250-267,H6包括残基273-286。
TY145样枯草杆菌酶已经表明缺乏熟知的BPN’枯草杆菌酶强离子结合位点。然而除了在BPN’枯草杆菌酶中也已知的弱钙或离子结合位点以外,TY145枯草杆菌酶还具有两个BPN’枯草菌素结构中不存在的离子结合位点。这可以在图3展示的结构比对中看到。这两个额外的离子结合位点在下文中根据它们与弱离子结合位点的距离称为“近”和“远”。因此与附录1中公开的原子坐标相关的,TY145的离子结合位点定位于PDB表中(附录1):
弱-命名为C314的钙原子、
近-命名为C312的钙原子,且
远-命名为C313的钙原子。
离子结合位点的位置可以通过与核心结构中4个特定原子的距离来定义。已经选定了离子结合位点到三个活性位点残基中c-α原子的距离。在全部枯草杆菌酶中活性位点的丝氨酸、组氨酸、天冬氨酸残基是高度保守的。TY145中它们是天冬氨酸35、组氨酸72和丝氨酸251。选定的第四个距离是与序列中活性位点丝氨酸残基后第一个氨基酸残基c-α原子的距离(后文称为“紧靠丝氨酸”);在TY145的3D结构中它是甲硫氨酸252。
在本发明的一个优选的实施方案中:
a)弱离子结合位点与i)天冬氨酸c-α原子间的距离为17.50-19.50_,与ii)组氨酸c-α原子间的距离为21-23_,与iii)丝氨酸c-α原子间的距离为13.80-15.80_,与iv)紧靠丝氨酸c-α原子间的距离为15.80-17.80_,
b)远离子结合位点与i)天冬氨酸c-α原子间的距离为28.70-30.70_,与ii)组氨酸c-α原子间为28-30_,与iii)丝氨酸c-α原子间为20-22_,与iv)紧靠丝氨酸c-α原子间为19.50-21.50_,
c)近离子结合位点与i)天冬氨酸c-α原子间为27-29_,与ii)组氨酸c-α原子间的距离为29.50-31.50_,与iii)丝氨酸c-α原子间的距离为21.40-23.40_,与iv)紧靠丝氨酸c-α原子间的距离为22.50-24.50_。
以下为TY145枯草杆菌酶中选定的4个c-α原子与3个离子结合位点间以_为单位的特定距离:
弱离子结合位点 | 远离子结合位点 | 近离子结合位点 |
甲硫氨酸252c-α原子16.75组氨酸72c-α原子 21.98天冬氨酸35c-α原子 18.55丝氨酸251c-α原子 14.71弱离子结合位点 0远离子结合位点 16.62近离子结合位点 9.79 | 20.3529.1029.6820.9616.62012.48 | 23.5830.4328.0422.289.7912.480 |
然而,这些距离在不同枯草杆菌酶中可能有所变化,且如前述弱离子结合位点也可以与钠离子结合。本距离以结构中为钙离子而给出。如果与钠离子结合,距离会略有迁移。通常距离可能变化±0.8_,优选±0.7_、±0.6_、±0.5_、±0.4_,或最优选±0.3_。
另外,TY145样枯草杆菌酶中,划定弱离子结合位点范围的肽结构由位于182-189和221-227的氨基酸残基组成,以G182、A187、L184残基主链羰基氧原子和两个水分子作为配位原子。
划定近离子结合位点范围的肽结构由212-225残基组成,以I220、T215残基主链羰基氧原子、D225和D218残基的羧酸氧和Q222残基的酰胺基团作为配位原子。
划定远离子结合位点范围的肽结构由288-306残基组成,以G298、G296和I289残基主链羰基氧原子、D300和D288残基的羧酸氧和两个水分子作为配位原子。
与BPN’样枯草杆菌酶结构相比,TY145样枯草杆菌酶的结构可以划分为“共有枯草杆菌酶样”区、“居间”区和“非同源”区。
可以在结构上与BPN’构密切相关的共有枯草杆菌酶样区发现活性位点。共有枯草杆菌酶样区由88-128和225-284残基组成,包含H3α螺旋和H5中心α螺旋,其中活性位点丝氨酸残基位于N端部分。共有枯草杆菌酶样区的RMS低于1.2。
共有枯草杆菌酶样区外,TY145样枯草杆菌酶与BPN’的结构存在更大程度的差异。
居间区由24-45、48-58、65-66、67-85、134-174、175-196、202-212和287-290残基组成。居间区的RMS高于1.2而低于1.8。TY145样枯草杆菌酶该区域的三维结构和功能性之间的关系可能难以预测。
非同源区由5-15、16-23、86-87、129-133、197-201、213-124、285-286、291-298和299-311残基组成。非同源区具有也属于居间区的65-66残基的高于1.5的RMS。包含5-15和299-311残基的基团具有2.1-2.2之间的RMS。TY145样枯草杆菌酶该区域三维结构和功能性之间的关系很难预测。
TY145结构中位于A1-T5、N16-T24、A46-Q51、S58-C66、G84-G90、S129-K134、S129-K134、S173-S175、V196-T201、N212-R224、A284-V286、K290-D299的区域的c-α原子坐标与其他S8枯草菌素家族(包括BPN’型枯草菌素)差异显著。由于在作比较的枯草杆菌酶中没有同源的c-α原子,所以无法计算这些最后的残基的RMS。
TY145和BPN’样枯草杆菌酶同源性的建立
TY145样枯草杆菌酶或BPN’样枯草杆菌酶的结构模型可以使用Homology程序或与之相当的程序如Modeller(都来自于MolecularSimulations,Inc.,San Diego,CA)来建立。原理为将3D结构已知的蛋白质的氨基酸序列与需要构建3D结构模型的蛋白质的氨基酸序列进行比对。可以基于共有序列建立结构保守区。在缺乏同源性的区域,可以通过例如Homology程序插入环结构或是删除序列,以使必要残基的顺次连接。接着应使用Homology或其他分子模拟程序(如MolecularSimulations的CHARMm)完成结构的松弛和优化。
设计TY145和枯草菌素家族枯草杆菌酶变体的方法
不同蛋白质分子动力学的比较可以提示哪些区域是重要的或提示哪些区域与每个蛋白质的某些特性相关。
本发明包括产生亲本TY145样枯草杆菌酶变体的方法,该变体与亲本TY145样枯草杆菌酶相比具有至少一项改变的特性,其方法包括:
a)在TY145枯草杆菌酶三维结构上建立亲本TY145枯草杆菌酶模型,以产生亲本TY145枯草杆菌酶的三维结构;
b)将步骤a)得到的三维结构与TY145枯草杆菌酶的三维结构进行比较;
c)基于步骤b)的比较鉴定出亲本TY145枯草杆菌酶的至少一个结构部分,其中预测该结构部分的改变将导致改变的特性;
d)修饰编码亲本TY145枯草杆菌酶的核酸序列,以产生编码在所述结构部分相应位置缺失或替换一个或多个氨基酸或在该结构部分插入一个或多个氨基酸残基的核酸序列;
e)在宿主细胞中表达修饰的核酸序列以产生变体TY145枯草杆菌酶;
f)分离产生的枯草杆菌酶;
g)纯化分离的枯草杆菌酶并
h)回收纯化的枯草杆菌酶。
另外本发明包括产生亲本枯草菌素家族枯草杆菌酶变体(如BPN’样枯草杆菌酶)的方法,该变体与亲本枯草菌素家族枯草杆菌酶相比具有至少一项改变的特性,其方法包括:
a)在枯草菌素家族枯草杆菌酶的三维结构上建立亲本枯草菌素家族枯草杆菌酶模型,以产生亲本枯草菌素家族枯草杆菌酶的三维结构;
b)将步骤a)中得到的三维结构与TY145枯草杆菌酶的三维结构进行比较;
c)基于步骤b)的比较鉴定出亲本枯草菌素家族枯草杆菌酶的至少一个结构部分,其中预测该结构部分的改变将导致改变的特性;
d)修饰编码亲本枯草菌素家族枯草杆菌酶的核酸序列以产生编码在所述结构部分相应位置缺失或替换一个或多个氨基酸或在该结构部分插入一个或多个氨基酸残基的核酸序列;
e)在宿主细胞中表达修饰的核酸序列以产生变体枯草菌素家族枯草杆菌酶;
f)分离产生的枯草杆菌酶;
g)纯化分离的枯草杆菌酶,并
h)回收纯化的枯草杆菌酶。
另外本发明包括产生亲本TY145样枯草杆菌酶变体的方法,该变体与亲本TY145样枯草杆菌酶相比具有至少一项改变的特性,该方法包括:
a)在TY145样枯草杆菌酶三维结构上建立亲本TY145样枯草杆菌酶模型以产生亲本TY145样枯草杆菌酶的三维结构;
b)将步骤a)得到的三维结构与枯草菌素家族枯草杆菌酶的三维结构进行比较;
c)基于步骤b)的比较鉴定出亲本TY145样枯草杆菌酶的至少一个结构部分,其中预测该结构部分的改变将导致改变的特性;
d)修饰编码亲本TY145样枯草杆菌酶的核酸序列以产生编码在所述结构部分相应位置缺失或替换一个或多个氨基酸或在该结构部分插入一个或多个氨基酸残基的核酸序列;
e)在宿主细胞中表达修饰的核酸序列以产生变体TY145样枯草杆菌酶;
f)分离产生的枯草杆菌酶;
g)纯化分离的枯草杆菌酶,并
h)回收纯化的枯草杆菌酶。
离子结合位点稳定性的改变
如前述,TY145枯草杆菌酶具有BPN’枯草菌素结构中不存在的两个新离子结合位点,但缺少BPN’枯草杆菌酶的强离子结合位点。离子结合位点的稳定性对酶的功能性是至关重要的。因此靠近离子结合位点的氨基酸残基的改变可能导致酶稳定性的改变。
已经定位了可被修饰的位置:
弱:在PDB表(附录1)中命名为C314的钙原子周围10_或更小的距离,
近:在PDB表(附录1)中命名为C312的钙原子周围10_或更小的距离,和
远:在PDB表(附录1)中命名为C313的钙原子周围10_或更小的距离。
更高的稳定性
可能可以通过TY145离子结合位点附近位置的改变而获得位点的稳定。位于TY145(SEQ ID NO:1)离子结合位点10_或更短距离内的位置为:
弱:154、155、158、164、165、166、167、168、178-191(即178、179、180、181、182、183、184、185、186、187、188、189、190、191)、211、220-228(即220、221、222、223、224、225、226、227、228)、277、281和305。
近:185、211-227(即211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、227)、277、281、299、300、301、304、305。
远:193、198、199、201、202、204、216、217、219、226、227、228、229和284-307(即284、285、286、287、288、289、290、291、292、293、294、295、296、297、298、299、300、301、302、303、304、305、306、307)。
在洗涤剂组合物中,钙螯合剂促成钙从枯草杆菌酶中离去,结果导致酶随后的失活。为降低例如由钙螯合剂引起的钙离去所导致的失活,可以构建具有更高的钙稳定性的变体。
靠近近离子结合位点发生改变的变体为I220S、T和T215S,靠近远离子结合位点发生改变的变体为G298A、S、T和G296A、S、T,靠近弱离子结合位点发生改变的变体为V185T和I221N、D、T。
具有额外离子结合位点的TY145
可以通过缺失(SEQ ID NO:1的)H83-G90区域或在其中进行缺失,并继而插入一个或多个氨基酸残基将来源于BPN’枯草杆菌酶的强离子结合位点移植到TY145(或TY145亚组中的其他枯草杆菌酶)中。优选的变体缺失了整个区域并继而在A82和V91之间插入了LNNSIG序列。
TY145离子结合位点的去除
通过去除离子结合位点可能改变酶对溶液中钙或其他离子的依赖性。BPN’和Savinase(或BPN’组中的其他酶)的三维结构可以指导移去除TY145(或TY145组的其它酶)中的远和近离子结合位点。
可以通过缺失(SEQ ID NO:1的)K290-D300区域或在其中进行缺失,并继而插入一个或多个氨基酸残基去除远位点。优选的变体缺失了整个区域并继而在I289和Y301之间插入了GDS或DST序列。另外优选的(而不是必须的)还进行S303Y替换。
可以通过缺失(SEQ ID NO:1的)N212-R224区域或在其中进行缺失,并继而插入一个或多个氨基酸残基去除近位点。优选的变体缺失了整个区域并继而在G211和D225之间插入了脯氨酸或丙氨酸。
BPN’枯草杆菌酶强离子结合位点的去除
BPN’样枯草杆菌酶的强离子结合位点可被移去。例如在Savinase中,可以通过缺失L75-G80区域(BPN’编号)或在其中进行缺失并继而插入一个或多个氨基酸残基而去除。优选的变体缺失了整个区域并继而插入了TY145的84-88残基。另外也可以应用L82Y和Q2AN替换。
热稳定性的改变
可以通过使用脯氨酸替换、引入二硫键、改变氢键触点、改变电荷分布、引入盐桥、用一个或多个具有更大侧链基团填充内部结构的空腔(如在结构可变区域)、用其他氨基酸替换组氨酸残基、去除脱酰胺作用位点、或螺旋加帽来获得具有更高稳定性的变体(通常是更高的热稳定性)。
提高活动性的区域
TY145的如下区域在酶的晶体结构中具有提高的活动性,现在认为这些区域与TY145的稳定性或活性有关。特别是可以通过改变高活动区域获得热稳定性。可以通过以下区域和位置的突变改良酶。在侧链引入例如更大的残基或具有更多原子的残基可以提高稳定性,或例如在侧链引入具有更少原子的残基可能对活动性重要并因此对酶活性分布重要。可以通过分析B-因子找到这些区域,B-因子取自附录1的坐标文件和/或均向波动(isotropic fluctuation)的分子动力学计算。这些可以使用MSI(Molecular Simulations Inc.)的CHARMm程序获得。
TY145在300K的分子动态模拟显示了如下高活动区:
84-89(即84、85、86、87、88)
108-117(即108、109、110、111、112、113、114、115、116、117)
141-146(即141、142、143、144、145、146)
150-152(即150、151、152)
169-171(即169、170、171)
200-201
211-220(即211、212、213、214、215、216、217、218、219、220)
242-243
268-270(即268、269、270).
晶体学数据的B-因子(参阅《in X-Ray Structure Determination》,Stout,G.K.和Jensen,L.H.,John Wiley & Sons,Inc.NY,1989)还提示了TY145结构中如下更具活动性的区域:
1-7(即1、2、3、4、5、6、7),
17-23(即17、18、19、20、21、22、23),
38-50(即38、39、40、41、42、43、44、45、46、47、48、49、50),
57-69(即57、58、59、60、61、62、63、64、65、66、67、68、69),
84-92(即84、85、86、87、88、89、90、91、92),
107-110(即107、108、109、110),
239-243(即239、240、241、242、243)及
265-266
优选57-69和84-92区域。
二硫键:
可以通过在结构域内或结构域间引入新的键获得与亲本TY145相比具有更高稳定性(例如热稳定性)的本发明TY145变体,如通过建立结构域内或结构域间的二硫键。
因此,本发明另一方面涉及产生亲本TY145变体的方法,包括本文“TY145样或BPN’样枯草杆菌酶变体的制备方法”段落所述的方法。
根据上文提到的指导方案,如下提到的在SEQ ID NO:1的氨基酸序列中鉴定出的氨基酸残基预计适于半胱氨酸取代。进行一个或多个半胱氨酸替换后,TY145的变体中可能形成二硫键。这些替换是:G26C+A95C;A167C+T254C;R203C+G292C和V228C+A284C。
通过寻找图1比对中的同源位置可以明确同源枯草杆菌酶(如TA39、TA41)中适于半胱氨酸取代的类似残基。对于其他TY145样序列,可以使用如前述的GAP分析法将所述TY145样序列与图1中全部序列进行比对来选择适于半胱氨酸取代的同源位置。然后,可以根据与图1中比对的枯草杆菌酶序列SEQ ID NO:1、2、3和4中最同源的同源位置选择合适的残基。
表面电荷分布
可以通过改变枯草杆菌酶的表面电荷分布获得与亲本枯草杆菌酶相比具有更高稳定性(通常为更高的热稳定性)的变体。例如,当pH低至约5或更低时,组氨酸残基通常带正电,因此,可能在蛋白质表面出现不利的静电相互作用。通过改变枯草杆菌酶的表面电荷可以避免这种不利的静电相互作用并继而导致枯草杆菌酶的更高的稳定性。
因此,本发明另外一方面涉及构建亲本枯草杆菌酶的变体的方法,其方法包括:
a)在亲本枯草杆菌酶表面,优选为TY145样或BPN’样枯草杆菌酶表面,鉴定出选自天冬氨酸、谷氨酸、精氨酸、赖氨酸和组氨酸的至少一个氨基酸残基;
b)在亲本枯草杆菌酶表面将选自天冬氨酸、谷氨酸、精氨酸、赖氨酸和组氨酸的至少一个氨基酸残基替换为不带电的氨基酸残基;
c)任选地循环重复步骤a)和b);
d)可选的,改变b)以外的一个或多个位置的氨基酸残基,改变可以分别为插入、缺失或替代;
e)制备从步骤a)到d)得到的变体;
f)测试所述变体的稳定性;并
g)可选地循环重复步骤a)到f);并
h)选择与亲本枯草杆菌酶相比具有更高稳定性的变体。
技术人员会理解,在某些情况下,把不带电的氨基酸残基替换为带电的氨基酸残基也可能是有利的,或另选地,在某些情况下将带电的氨基酸残基替换为带相反电荷的氨基酸残基也可能是有利的。因此,技术人员也可以为了这些目的方便的使用前文提到的方法。在使用前述方法将不带电的氨基酸残基替换为带电的氨基酸残基时,唯一的区别是步骤a)和b)改变如下:
a)在亲本枯草杆菌酶表面鉴定出至少一个不带电的氨基酸残基;
b)在亲本枯草杆菌酶表面将至少一个不带电的氨基酸残基替换为选自天冬氨酸、谷氨酸、精氨酸、赖氨酸和组氨酸的带电的氨基酸残基;
也可以使用前文提到的方法改变枯草杆菌酶表面氨基酸残基的电荷符号。与前述方法相比,唯一的区别仍然是步骤a)和b),在此情况下,应为:
a)在亲本枯草杆菌酶表面鉴定出至少一个选自天冬氨酸、谷氨酸、精氨酸、赖氨酸和组氨酸的带电氨基酸残基;
b)在亲本枯草杆菌酶表面将至少一个步骤a)中鉴定出的带电氨基酸残基替换为带相反电荷的氨基酸残基。
因此,天冬氨酸可以替换为精氨酸、赖氨酸或组氨酸;谷氨酸可以替换为精氨酸、赖氨酸或组氨酸;精氨酸可以替换为天冬氨酸或谷氨酸;赖氨酸可以替换为天冬氨酸或谷氨酸;组氨酸可以替换为天冬氨酸或谷氨酸。
为检测存在于枯草杆菌酶表面的氨基酸残基,使用DSSP程序(Kabsch和Sander,Biopolymers(1983),22,2577-2637)测量表面可接近区。所有表面可接近性大于0的残基都认为是表面残基。
使用上述方法在TY145表面发现的一个氨基酸残基为D116,预期D116H、K、R的替换特别具有意义。
类似的替换可以在其他TY145样枯草杆菌酶的等效位置引入。
用脯氨酸残基替换
可以通过如下手段提高枯草杆菌酶的热稳定性:对所述枯草杆菌酶进行二级结构的分析、鉴定二面角Φ(phi)和Ψ(psi)限定于区间[-90°<Φ<-40°和-180°<Ψ<180°]的残基,优选区间[-90°<Φ<-40°和120°<Ψ<180°]或[-90°<Φ<-40°和-50°<Ψ<10°]并排除位于枯草杆菌酶特征性α螺旋或β片层区域的残基。
基于结晶枯草杆菌酶的原子结构计算出氨基酸的二面角Φ(phi)和Ψ(psi)之后,可能选择出具有适于脯氨酸残基替换的二面角phi和psi的位置。脯氨酸残基的脂肪侧链与肽基团的氮原子共价结合。形成的五员环因此对肽主链的N-Cα键的旋转施加了刚性约束,同时阻止了与主链N原子氢键的形成。由于这些结构上的原因,脯氨酸残基通常与α螺旋和β片层二级构象不相容。
如果在鉴定的位置没有脯氨酸,就以脯氨酸残基代替天然存在的氨基酸残基,优选通过在编码所述枯草杆菌酶的基因上应用位点定向诱变。
TY145样枯草杆菌酶组中脯氨酸残基可以引入到位置18、115、185、269和293。因此,优选的TY145变体具有一个或多个以下置换:Q18P、D115P、V185P、T269P和I293P。
活性的改变
在TY145和Savinase中引入低温活性
进行了TY145(从晶体结构中得到的嗜温衍生酶)和TA41(从建模中得到的嗜冷衍生酶)在300K的分子动力学比较。
比较关注于低温活性并揭示了TY145和TA41动力学行为差异。从比较中得出的理论是动力学差异(特别是在活性位点周围)对嗜冷酶的低温功能性是重要的。酶具有低温活性需要必要的动力学,因此如果酶动力学降低则活性下降。
通过分子动力学模拟测量出的TA41中与TY145相比更高活动性的区域表明了TA41酶中对低温活性重要的区域,该区域可以转移到TY145中。
TA41的这些区域为:
16-22(即16、17、18、19、20、21、22)、
40-73(即40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73)、
118-131(即118、119、120、121、122、123、124、125、126、127、128、129、130、131)
140-161(即140、141、142、143、144、145、146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161)和
275-294(即275、276、277、278、279、280、281、282、283、284、285、286、287、288、289、290、291、292、293、294)。
最靠近活性位点和底物结合位点的区域就使TY145产生更高的低温活性而言被认为是优选的:40-73和140-161,优选65-73和140-150。TY145的这些区域应被修饰的更具活动性,例如在TY145主链中用小的较柔软残基即具有较小侧链的残基(如甘氨酸、丙氨酸、丝氨酸、苏氨酸或缬氨酸)替代。
TA41的其他区域和嗜冷酶的稳定性高度相关。
这些区域很容易在TA39中或其他同源酶及非嗜冷酶中发现。
活性位点和底物结合位点周围的区域是最有可能与低温功能性相关的区域。
以下是将TA41低温活性和同源序列转入TY145样序列和BPN’样序列的建议:
TA41 | TY145 | Savinase |
I31V38S79A80L81V187T253 | V31I、A、LV38A、LT79SV80A、G、VL81GV188AT254S、A | V28I、A、LI35V、A、LT71SI72A、G、VA73L、GM175V、AT224S、A |
分别根据SEA ID NO:3、1和5编号。Savinase根据BPN’编号。
优选的Savinase变体为V28I、I35V、T71S、I72A、A73L、M175V和T224S。
TY145核心变体的实例为:V31I、V80A、T79S。
TY145样序列和BPN’样序列的改变可以是单突变或者是所建议突变的组合。
底物结合位点
底物结合位点通过与底物模型(如CI2抑制子)接触的残基鉴定。可在附录1中找到在CI2结合于活性位点的TY145枯草杆菌酶的3D结构坐标。不限于其他理论,现认为在距底物分子10_范围内特别是距底物分子6_范围内发现的有利的相互作用支持了底物与酶的结合。这些有利键的实例为氢键、强静电作用和/或疏水相互作用。
TY145枯草杆菌酶(SEQ ID NO:1)的以下残基与CI2抑制子距离在6_以内,因此相信它们涉及所述底物的相互作用:
35、36、70、72、106、109、110、111、112、113、114、117、139、140、141、142、143、144、145、147、150、167、168、169、170、171、172、173、174、177、180、207、239、247、148、149、150、151和252。
通过修饰天冬酰胺-甘氨酸对的稳定
已知在碱性pH下,天冬酰胺的侧链可以和与其后续相邻氨基酸的NH基团相互作用形成异天冬氨酸残基,其主链经过天冬氨酸侧链。这使主链对蛋白酶解作用更加脆弱。如果其后的氨基酸为甘氨酸则更容易发生脱酰胺作用。改变甘氨酸或它前面的天冬氨酸可以避免这种情况的发生从而提高稳定性,特别是所关心的热和贮存稳定性。
因此本发明另外还涉及枯草杆菌酶,其中亲本RP-II蛋白酶氨基酸序列中出现的任一天冬酰胺-甘氨酸序列的二残基之一或二者全部缺失或被不同的氨基酸残基替换。
例如,天冬酰胺和/或甘氨酸残基可被选自A、Q、S、P、T和Y的的氨基酸残基替换。
可在以下位置发现天冬酰胺-甘氨酸序列:
B.sphaericus:198-199、240-241
TY145:87-88、109-110、199-200
TA41:83-84、198-199
TA39:88-89、198-199
因此本发明这一方面涉及根据前文给出的原则在一个或多个这些位置上的修饰(如缺失或替换)。
酪氨酸残基的修饰
就洗涤性能而言,已经发现将某些酪氨酸残基修饰为苯丙氨酸提供了更好的洗涤性能。不限于任何特定理论的,据认为碱性洗涤液中这些酪氨酸残基的滴定具有负效果,通过用其他残基,特别是苯丙氨酸和色氨酸,尤其是苯丙氨酸替换酪氨酸残基可减弱其负效果。
可在以下位置发现酪氨酸:
B.sphaericus:14、91、102、112、155、157、172、179、201、206、211、218、235、239、243、292、300,
TY145:15、39、92、103、113、156、158、202、219、240、244、287、301、307,
TA41:15、91、102、112、155、157、179、201、218、235、243、
TA39:15、61、91、102、112、155、157、173、179、201、211、218、235、243、267、281、284、292、293、296
因此本发明这一方面涉及根据前文给出的原则在一个或多个这些位置上的修饰(如缺失或替换)。
甲硫氨酸残基的修饰
为改进蛋白质的氧化稳定性,已经发现甲硫氨酸残基的替换甚至缺失是有利的。特别是通常紧靠活性丝氨酸残基的甲硫氨酸残基的修饰可以使氧化稳定性显著提高。修饰成丝氨酸或丙氨酸是该甲硫氨酸最优选的替换。
甲硫氨酸可在以下位置发现:
B.sphaericus:138、251、
TY145:139、252、
TA41:1、138、251、
TA39:1、138、251、
因此本发明这一方面涉及根据前文给出的原则在一个或多个这些位置上的修饰(如缺失或替换)。
组合修饰
本发明还包括与其氨基酸序列的任一其他修饰组合的任何前述枯草杆菌酶变体。特别是设想了为提供酶的改进特性而与本领域其他已知修饰组合。
这些组合包括以下位置:222(提高氧化稳定性)、218(提高热稳定性)、使酶稳定的Ca2+结合位点替换(例如位置76),以及现有技术中许多其它显然的位置(所有位置按照BPN’编号)。
在还有的实施方案中,本文所述枯草杆菌酶变体可有利地组合有以下任何位置中的一个或多个修饰:
27、36、56、76、87、95、96、97、98、99、100、101、102、103、104、120、123、159、167、170、206、218、222、224、232、235、236、245、248、252和274(BPN′编号)。
特别地,下列BLSAVI、BLSUBL、BSKSMK和BAALKP修饰认为适宜组合:
K27R、*36D、S56P、N76D、S87N、G97N、S101G、S103A、V104A、V104I、V104N、V104Y、H120D、N123S、G159D、Y167A、R170S、R170L、Q206E、N218S、M222S、M222A、T224S、A232V、K235L、Q236H、Q245R、N248D、N252K和T274A(BPN′编号)。
另外,包含下述修饰的变体表现出改进的特性,其修饰包括S101G+V104N、S87N+S101G+V104N、K27R+V104Y+N123S+T274A、N76D+S103A+V104I或N76D+V104A,或修饰K27R、N76D、S101G、S103A、V104N、V104Y、V104I、V104A、N123S、G159D、A232V、Q236H、Q245R、N248D、N252K、T274A与一个或多个任何前文提及的修饰的组合。
特别值得注意的变体为除了符合本发明的修饰以外,还包含了如下替换的变体:S101G+S103A+V104I+G159D+A232V+Q236H+Q245R+N248D+N252K。
另外,本发明主要方面的枯草杆菌酶变体优选组合有129、131和194中任一位置的一个或多个修饰,优选129K、131H和194P修饰,最优选P129K、P131H和A194P修饰。任何这些修饰可望在其生产中提供更高的枯草杆菌酶变体表达水平。
TY145样或BPN’样枯草杆菌酶变体的制备方法。
本发明枯草杆菌酶变体,即TY145和BPN’变体可通过本领域中任何已知方法产生,本发明还涉及编码本发明枯草杆菌酶变体的核酸、包含所述核酸序列的DNA构建体以及含有所述核酸序列的宿主细胞。
通常天然存在蛋白质可通过培养表达该蛋白质的生物然后纯化蛋白质来生产,也可以通过将编码该蛋白质的核酸(如基因组DNA或cDNA)克隆进表达载体,将所述表达载体引入宿主细胞,培养宿主细胞并纯化表达的蛋白质来生产。
一般可通过亲本蛋白质的位点定向诱变、引入表达载体、宿主细胞等产生蛋白质变体。亲本蛋白质可从产生该多肽的菌株中或从表达文库中克隆,即,可从基因组DNA中分离或从cDNA中制备,或从它们的组合中产生。
通常可以使用标准操作克隆基因和/或将(随机和/或位点定向)突变引入所述基因以获得亲本枯草杆菌酶,或获得本发明枯草杆菌酶或枯草杆菌酶变体。适用技术的进一步描述可参考《Molecular cloning:Alaboratory manual》(Sambrook等,(1989),Cold Spring Harbor lab,Cold Spring Harbor,NY;Ausubel,F.M.等);《Current protocolsin Molecular Biology》(John Wiley和Sons,1995;Harwood,C.R.和Cutting,S.M.);《Molecular Biological Methods for Bacillus》(JohnWiley和Sons,1990);《DNA Cloning:A Practical Approach》卷I和II(D.N.Glover编,1985);《Oligonucleotide Synthesis》(M.J.Gait编,1984);《Nucleic Acid Hybridization》(B.D.Hames & S.J.Higgins编,(1985));《Transcription And Translation》(B.D.Hames & S.J.Higgins编,(1984))《Animal Cell Culture》(R.I.Freshney编,(1986));《Immobilized Cells And Enzymes》(IRL Press,(1986));《A PracticalGuide To Molecular Cloning》(B.Perbal,(1984))和WO 96/34946。
另外,变体构建可通过:
随机诱变
随机诱变适合在翻译成所探讨氨基酸序列的基因中至少3个部分或在整个基因中进行,随机诱变既可以是局部也可以是区域专一的。
可以使用本领域任何已知方法方便的进行编码亲本枯草杆菌酶的DNA序列的随机诱变。
就上文而言,本发明另一方面涉及产生亲本枯草杆菌酶变体的方法,其变体相对于亲本枯草杆菌酶表现出改变的特性,如更高的热稳定性、在低pH和低钙浓度下更高的稳定性,其方法包括:
(a)对编码亲本枯草杆菌酶的DNA序列进行随机诱变,
(b)在宿主细胞中表达步骤(a)得到的突变DNA序列,并
(c)筛选表达相对于亲本枯草杆菌酶具有改变特性的枯草杆菌酶变体的宿主细胞。
优选使用搀杂引物(doped priner)实施本发明前述方法的步骤(a)。例如,可通过使用适当的物理或化学诱变剂、使用适当的寡核苷酸、或是使DNA序列经产生诱变的PCR来进行随机诱变。此外,可以通过使用这些诱变剂的任一组合进行随机诱变。诱变剂可以是例如诱导转换、易位、倒位、混乱(scramblimg)、缺失和/或插入的诱变剂。
适合本发明目的的物理或化学诱变剂实例包括紫外线(UV)照射、羟胺、N-甲基-N′-硝基-N-亚硝基胍(MNNG)、邻-甲基羟胺、亚硝酸、乙基甲烷磺酸酯(EMS)、亚硫酸氢钠、甲酸和核苷酸类似物。使用这些试剂时,一般通过将用于诱变的编码亲本酶的DNA序列在选定的诱变剂存在时在适合发生诱变的条件下孵育而进行诱变,然后选择具有所需特性的突变DNA。
使用寡核苷酸进行诱变时,在寡核苷酸合成中寡核苷酸可在需要改变的位置搀杂或混入三种非亲本核苷酸。可以通过该搀杂或混入避免不需要的氨基酸的密码子。可通过任何公开的技术将搀杂或混入的寡核苷酸整合入编码枯草杆菌酶的DNA中,例如使用PCR、LCR或认为合适的任何DNA聚合酶和连接酶。
优选使用“恒量随机掺杂(constant random doping)”进行搀杂,其中每一位置野生型和修饰的百分比是预先确定的。另外,可以指导掺杂,以优选引入某核苷酸并从而优选引入一个或多个特定氨基酸残基。可以为了例如在每一位置引入90%野生型和10%修饰而进行搀杂。选择搀杂方案另外需要的考虑是基于遗传的及蛋白质结构的限制。搀杂方案可以使用DOPE程序制作,它特别保证了避免引入终止密码子(L.J.Jensen等,Nucleic Acid Research,26,697-702(1998)。
使用PCR产生的诱变时,经化学处理或未经化学处理的编码亲本枯草杆菌酶的基因在可增加核苷酸错误掺入条件下进行PCR(Deshler1992;Leung等,Technique,1,1989,pp.11-15)。大肠杆菌的增变株(Fowler等,Molec.Gen.Genet,133,1974,179-191)、酿酒酵母(S.cereviseas)或任意其他微生物均可用于编码枯草杆菌酶的DNA的随机诱变,通过例如将含有亲本酶的质粒转化入增变株、培养含有该质粒的增变株并从增变株中分离突变质粒进行诱变。继而可将突变质粒转化入表达生物中。
用于诱变的DNA序列可以便利地存在于从表达亲本枯草杆菌酶的生物中制备的基因组或cDNA文库。另外,DNA序列可以存在于合适的载体(如质粒或噬菌体)中,并可这样与诱变剂孵育或暴露于诱变剂。用于诱变的DNA也可以通过整合入宿主细胞的基因组或存在于停靠在宿主细胞内的载体上而存在于宿主细胞中。最后,用于诱变的DNA可以为分离的形式。应该理解用于随机诱变的DNA序列优选为cDNA或基因组DNA序列。
在某些情况下可以方便地在实施表达步骤b)或筛选步骤c)之前扩增突变DNA序列。可以按照本领域已知方法进行这类扩增,目前优选的方法为使用基于亲本酶DNA或氨基酸序列制备的寡核苷酸引物的PCR产生的扩增。
与诱变剂孵育或暴露于诱变剂之后,通过在允许表达发生的条件下培养携带DNA序列的适当宿主细胞表达突变DNA。为此目的使用的宿主细胞可以已转化突变的DNA序列(任选地存在于载体上),或者在诱变处理中携带编码亲本酶的DNA序列。合适的宿主细胞实例如下:革兰氏阳性细菌如枯草芽孢杆菌(Bacillus subtilis)、地衣芽孢杆菌(B.1icheniformis)、迟缓芽孢杆菌(B.lentus)、短芽孢杆菌(B.brevis)、嗜热脂肪芽孢杆菌、嗜碱芽孢杆菌(B.alkalophilus)、解淀粉芽孢杆菌(B.amyloliquefaciens)、凝结芽孢杆菌(B.coagulans)、环状芽孢杆菌(B.circulans)、灿烂芽孢杆菌(B.lautus)、巨大芽孢杆菌(B.megaterium)、苏云金芽孢杆菌(B.thuringiensis)、变铅青链霉菌(S.lividans)或鼠灰链霉菌(S.murinus),及革兰氏阴性细菌如大肠杆菌(Echerichia coli)。
突变DNA序列另外还可以含有编码允许突变DNA序列表达的功能的DNA序列。
局部随机诱变
将随机诱变限制在目的亲本枯草杆菌酶中的一部分可能是有利的。例如当已鉴定出酶的某一区域对酶的给定特性具有特别的重要性,并期望修饰后导致变体具有改进特性时,它可能是有利的。这些区域通常可在亲本酶的三级结构已被阐明并与酶的功能相联系后鉴定出来。
局部或区域特异性的随机诱变可以使用如前述PCR产生的诱变技术或任何其他本领域的已知技术方便的实现。另外,可分离编码欲修饰的DNA序列部分的DNA序列(例如通过插入适当的载体),并继而将所述部分通过使用任一前文讨论的诱变方法实施诱变。
使用DOPE程序随机诱变的一般方法
可以通过以下步骤进行随机诱变:
1.选择亲本酶中用于修饰的目的区域
2.确定选定区域中的突变和非突变位点
3.根据要构建的变体需要的稳定性和/或性能决定进行哪种突变
4.选择结构上合理的突变
5.根据步骤4调整步骤3中选出的残基
6.使用适当的掺入算法(dope algorithm)分析核苷酸分布
7.如果必要的话,根据遗传密码的实际情况调整需要的残基,例如考虑由遗传密码产生的限制(例如为避免引入终止密码子);技术人员应意识到某些密码子组合实际上不能使用而需要调整
8.制备引物
9.使用引物进行随机诱变
10.通过筛选需要的改进特性选择得到的枯草杆菌酶变体。
步骤6中使用的适当的掺入算法为本领域所熟知。Tomandl,D等在1997,Journal of Computer-Aided Molecular Design 11:29-38中描述了一个这样的算法,另一个算法是DOPE(Jensen,LJ,Andersen,KV,Svendsen,A和Kretzschmar,T(1998)Nucleic Acids Research26:697-702)。
表达载体
含有编码本发明枯草杆菌酶变体的核酸序列的重组表达载体可以是任何便于进行重组DNA操作并引起该核酸序列表达的载体。
载体的选择通常取决于它将被引入的宿主细胞。适宜载体的实例包括线性或闭合的环状质粒或病毒。载体可以是自主复制载体,即载体作为染色体外的实体存在,其复制不依赖于染色体复制,例如质粒、染色体外元件、微染色体或人工染色体。载体可以含有保证自我复制的任何手段。细菌复制起点的实例为质粒pBR322、pUC19、pACYC177、pACYC184、pUB110、pE194、pTA1060和pAMβ1的复制起点。酵母宿主细胞中使用的复制起点的实例为2μ复制起点、CEN6和ARS6的组合、以及CEN3和ARS1的组合。复制起点可以包含使其在宿主细胞中以温度敏感的方式行使功能的突变(参见如Ehrlich,1978,Proceedingsof the National Academy of Sciences USA 75:1433)。
或者,载体可以在引入宿主细胞后整合入基因组,并与其整合的染色体一起复制。整合入宿主细胞基因组的载体可以包含任何使其能整合入基因组的核酸序列,特别是可以包含便于通过同源或非同源重组整合的核酸序列。载体系统可以是单个载体(例如质粒或病毒),或者是一起包含需引入宿主基因组的全部DNA的两个或多个载体(例如质粒或病毒),或转座子。
具体而言,载体可以是表达载体,其中编码本发明枯草杆菌酶变体的DNA序列与DNA转录需要的附加片段或控制序列有效连接。术语“有效连接”表示以使片段以与预期目的一致的方式发挥功能的排列,例如转录在启动子处起始并通过编码枯草杆菌酶变体的DNA序列延伸。附加的片段或控制序列包括启动子、前导序列、多腺苷酸化序列、前肽序列、信号序列和转录终止子。控制序列最少包括启动子和转录及翻译终止信号。
启动子可以是在选择的宿主细胞中表现转录活性的任何DNA序列,它可来自编码与宿主细胞同源或异源的蛋白质的基因。
适宜在细菌宿主细胞中使用的启动子的实例为以下基因的启动子:枯草芽孢杆菌果聚糖蔗糖酶基因(sacB)、嗜热脂肪芽孢杆菌麦芽糖淀粉酶基因(amyM)、地衣芽孢杆菌α-淀粉酶基因(amyL)、解淀粉芽孢杆菌α-淀粉酶基因(amyQ)、枯草芽孢杆菌碱性蛋白酶基因,或短小芽孢杆菌木糖苷酶基因、解淀粉芽孢杆菌BAN淀粉酶基因、地衣芽孢杆菌青霉素酶基因(penP)、枯草芽孢杆菌xylA和xylB基因,以及原核β-内酰胺酶基因(Villa-Kamaroff等,1978,Proceedings of theNational Academy of Sciences USA 75:3727-3731)。其他实例包括λ噬菌体PR或PL启动子或大肠杆菌lac、trp或tac启动子或天蓝色链霉菌(Streptomyces coelicolor)琼脂糖基因(dagA)。其他启动子描述于Useful proteins from recombinant bacteria,Scientific American,1980,242:74-94及Sambrook等,1989,见前文。
适宜在丝状真菌宿主细胞中使用的启动子实例为从以下基因中得到的启动子:米曲霉(Aspergillus oryzae)TAKA淀粉酶、米赫根毛霉(Rhizomucor miehei)天冬氨酸蛋白酶、黑曲霉(Aspergillus niger)中性α淀粉酶、黑曲霉酸稳定α淀粉酶、黑曲霉或泡盛曲霉(Aspergillusawamori)葡糖淀粉酶(glaA)、米赫根毛霉脂肪酶、米曲霉(Aspergillusoryzae)碱性蛋白酶、米曲霉丙糖磷酸异构酶、构巢曲霉(Aspergillusnidulans)乙酰胺酶和尖孢镰孢(Fusarium oxysporum)胰蛋白酶样蛋白酶(如此处引为参考的U.S.Patent No.4,288,627中所述),及这些启动子的杂合体。特别地,在丝状真菌宿主细胞中使用的启动子优选为TAKA淀粉酶、NA2-tpi(来自编码黑曲霉中性淀粉酶和米曲霉丙糖磷酸异构酶的基因的启动子的杂合体)和glaA启动子。另外的适宜在丝状霉菌宿主细胞中使用的启动子为ADH3(McKnight等,The EMBO J.4(1985),2093-2099)启动子或tpiA启动子。
适宜在酵母宿主细胞中使用的启动子实例包括以下基因的启动子:酵母糖酵解基因(Hitzeman等,J.Biol.Chem.255(1980),12073-12080;Alber and Kawasaki,J.Mol.Appl.Gen.1(1982),419-434)或醇脱氢酶基因(Young等,in Genetic Engineering of Microorganismsfor Chemicals(Hollaender等编辑),Plenum Press,New York,1982),或TP11(US 4,599,311)或ADH2-4c(Russell等,Nature 304(1983),652-654)启动子。
其他有用的启动子可得自酿酒酵母烯醇化酶(ENO-1)基因、酿酒酵母半乳糖激酶基因(GAL1)、酿酒酵母醇脱氢酶/甘油醛-3-磷酸脱氢酶(ADH2/GAP)和酿酒酵母3-磷酸甘油酸激酶基因。用于酵母宿主细胞的其它有用的启动子如Romanos等,1992,Yeast 8:423-488所述。在哺乳动物宿主细胞中,有用的启动子包括得自猿猴病毒40(SV40)、劳氏肉瘤病毒(RSV)、腺病毒和牛乳头状瘤病毒(BPV)的启动子。
适宜在哺乳动物细胞中使用的启动子实例为SV40启动子(Subramani等,Mol.Cell Biol.1(1981),854-864),MT-1(金属硫蛋白基因)启动子(Palmiter等,Science 222(1983),809-814)或腺病毒2主要晚期启动子。
适宜在昆虫细胞中使用的启动子实例为多角体蛋白启动子(US4,745,051;Vasuvedan等,FEBS Lett.311,(1992)7-11)、P10启动子(J.M.Vlak等,J.Gen.Virology 69,988,765-776页)、苜蓿银纹夜蛾多角体病毒碱性蛋白启动子(EP 397485)、杆状病毒立即早期基因1启动子(US5,155,037;US5,162,222)或杆状病毒39K延迟早期基因启动子(US5,155,037;US5,162,222)。
必要时编码本发明枯草杆菌酶变体的DNA序列也可以与适当的终止子有效连接。
本发明重组载体另外还可以含有使载体在目的宿主细胞中复制的DNA序列。
载体还可以含有选择标记,例如,其产物互补了宿主细胞中缺陷的基因,或者编码抗性的基因,如抗氨卡青霉素、卡那霉素、氯霉素、红霉素、四环素、壮观霉素、新霉素、潮霉素、氨甲蝶呤等抗生素的抗性基因,或者抗重金属、病毒或除草剂的抗性基因,或其产物造成原养型或营养缺陷型的基因。细菌选择标记的实例是来自枯草杆菌或地衣芽孢杆菌的dal抗性基因。常常使用的哺乳动物标记是二氢叶酸还原酶基因(DHFR)。适用于酵母宿主细胞的标记是ADE2、HIS3、LEU2、LYS2、MET3、TRP1和URA3。用于丝状真菌宿主细胞的选择性标记可选自(但不限于)以下基因:amdS(乙酰胺酶)、argB(鸟氨酸氨甲酰基转移酶)、bar(膦丝菌素乙酰转移酶)、hygB(潮霉素磷酸转移酶)、niaD(硝酸还原酶)、pyrG(乳清酸核苷-5’-磷酸脱羧酶)、sC(硫酸腺苷酰转移酶)、trpC(氨基苯甲酸合酶)和glufosinate抗性标记,以及来自其它物种的等价物。具体而言,用于曲霉细胞中的是构巢曲霉或米曲霉的amdS和pyrG标记以及吸水链霉菌(Streptomyceshygroscopicus)的bar标记。此外,可以通过共转化完成选择,如WO91/17243所述,其中选择性标记在分开的载体上。
为了指导本发明枯草杆菌酶变体进入宿主细胞的分泌途径,可在重组载体中提供分泌信号序列(也称为前导序列、前原序列或前序列)。分泌信号序列在正确的阅读框中与编码所述酶的DNA序列连接。分泌信号序列通常置于编码该酶的DNA序列的5’端。分泌信号序列可以是正常与该酶关联的序列,或者可以来自编码另一分泌蛋白质的基因。
用于分别连接编码本发明酶的DNA序列、启动子以及任选的终止子和/或分泌信号序列,或者通过适当的PCR扩增方案装配这些序列并将它们插入含复制或整合所必需信息的合适载体的技术都是本领域技术人员所熟知的(例如,见Sambrook等)。
可以将一个以上拷贝的编码本发明酶的核酸序列插入宿主细胞中以扩大核酸序列的表达。用本领域所熟知的方法将至少一个额外拷贝的序列整合入宿主细胞中并对转化体进行选择可以实现核酸序列的稳定扩增。
本发明的核酸构建体还可包含编码一种或多种有利于多肽表达的因子的一个或多个核酸序列,例如,激活子(如反式作用因子)、陪伴分子和加工蛋白酶。在所选宿主细胞内起作用的任何因子都可用于本发明中。编码一个或多个这样因子的核酸不一定与编码本发明多肽的核酸串联。
宿主细胞
编码本发明枯草杆菌酶变体的DNA序列对于其所引入的宿主细胞可以是同源或异源的。如果与宿主细胞同源,即,由宿主细胞天然产生,它通常有效连接于非其天然环境中的另一启动子序列,或者,如果适当的话,另一分泌信号序列和/或终止序列。术语“同源的”旨在包括所编码酶对于所述宿主生物体是天然酶的DNA序列。术语“异源的”旨在包括不是由宿主细胞天然表达的DNA序列。从而,DNA序列可以来自另一生物,或者可以是合成的序列。
本发明的DNA构建体或重组载体所引入的宿主细胞可以是能生产本发明枯草杆菌酶变体的任何细胞,诸如原核生物(如细菌等)或真核生物,如酵母或丝状真菌等真菌细胞、昆虫细胞、植物细胞或哺乳动物细胞。
培养时能产生本发明枯草杆菌酶变体的细菌宿主细胞的实例为革兰氏阳性菌,如芽孢杆菌,如枯草杆菌、地衣芽孢杆菌、迟缓芽孢杆菌(B.lentus)、短芽孢杆菌(B.brevis)、嗜热脂肪芽胞杆菌、嗜碱芽孢杆菌(B.alkalophilus)、解淀粉芽孢杆菌、凝结芽胞杆菌(B.coagulans)、环状芽胞杆菌(B.cirulans)、灿烂芽孢杆菌(B.lautus)、巨大芽孢杆菌(B.megaterium)或苏云金芽孢杆菌(B.thuringiensis)等菌株,或变铅青链霉菌(S.lividans)或鼠灰链霉菌(S.murinus)等链霉菌(streptomyces)菌株,或者是大肠杆菌(E.cdi)或假单胞菌(Pseudomonas sp.)等革兰氏阴性细菌。
可通过原生质体转化、电穿孔、接合或通过用感受态细胞以本质已知的方式完成细菌的转化(参见,Sambrook等,见上文)。
当枯草杆菌酶变体在大肠杆菌等细菌内表达时,所说的酶可以保留在细胞质内,通常作为不溶性颗粒(称作包涵体),或者可以在细菌分泌序列的引导下进入周质间隙。在前一种情况下,裂解细胞,回收颗粒并进行变性,然后通过稀释变性剂使酶重折叠。在后一种情况下,可以通过用超声波或渗压休克法等方法破坏细胞,释放周质间隙内容物并回收所述酶,从而从周质间隙中回收到所述酶。
当在芽孢杆菌或链霉菌菌株等革兰氏阳性菌中表达枯草杆菌酶变体时,所说的酶可以保留在细胞质中,或者可以在细菌分泌序列的指引下到达细胞外培养基。在后一种情况下,按下文所述从培养基中回所述酶。
宿主酵母细胞的例子包括假丝酵母属(candida)、克鲁维酵母属(kluyveromyces)、酵母属(saccharomyces)、裂殖酵母属(schizosaccharomyces)、假丝酵母(candida)、毕赤氏酵母(Pichia)、汉逊酵母(Hansenula)或Yarrowia属种的细胞。在一个具体的实施方案中,酵母宿主细胞是卡尔酵母(S.carlsbergensis)、酿酒酵母(S.cerevisiae)、糖化酵母(S.diastaticus)、saccharomyces douglasii、克鲁弗酵母(S.kluyveri)、诺地酵母(saccharomyces norbensis)或卵形酵母(S.oviformis)细胞。其它有用的酵母宿主细胞是乳酸克鲁维酵母(kluyveromyces lactis)、脆壁克鲁维酵母(Kluyveromyces fragilis)、多形汉逊酵母(Hansenula polymorpha)、巴斯德毕赤酵母(Pichiapastoris)、Yarrowia lipolytica、粟酒裂殖酵母(Schizosaccharomycespombe)、玉蜀黍黑粉菌(Ustilgo maylis)、Candida maltose、季尔蒙氏毕赤酵母(Pichia guillermondii)和Pichia methanolio细胞(参阅,Gleeson等,J.Gen.Microbiol.132,1986,3459-3465页;US4882279和US4879231)。因为酵母的分类在未来有可能会改变,就本发明的目的而言,应按如下文献所述定义酵母:《Biology and Activities of Yeast》(Skinner,F.A.,Passmore,S.M.,和Davenport,R.R.编,Soc.App.Bacteriol.Symposium Series No.9,1980)。酵母的生物学和酵母遗传操作是本领域所熟知的(参阅,如,《Biochemistry andGenetics of Yeast,Bacil》,M.,Horecker,B.J.,和Stopani,A.O.M.编,第二版,1987;《The Yeasts》,Rose,A.H.,和Harrison,J.S.编,第二版,1987;和《The Molecular Biology of the YeastSaccharomyces》,Strathem等编,1981)。可以用以下文献所述的方法转化酵母:Becker和Guarente,In Abelson,J.N.和Simon,M.I.编,Guide to Yeast Genetics and Molecular Biology,Methods inEnzymology,第194卷,第182-187页,Academic Press Inc.,New York;Ito等,1983,Journal of Bacteriology 153:163;和Hinnen等,1978,Proceeding of the National Academy of Sciences USA 75:1920。
丝状真菌细胞的实例包括丝状形式的真菌亚门(Eumycota)和卵菌亚门(Oomycota)(按如下定义:Hawksworth等,1995,同上引文),尤其是它可以是以下菌属的细胞:枝顶孢属(Acremonium),如A.chrysogenum等;曲霉属(Aspergillus),如泡盛曲霉(A.awamori)、臭曲霉(A.foetidus)、日本曲霉(A.japonicus)、黑曲霉(A.niger)、构巢曲霉(A.nidulans)或米曲霉(A.oryzae);镰孢霉(Fusarium),如杆孢状镰孢(F.bactridioides)、F.cerealis、F.crookwellense、大刀镰孢(F.culmorum)、禾本科镰孢(F.graminerarum)、禾赤镰孢(F.graminum)、异孢镰孢(F.heterosporum)、合欢木镰孢(F.negundi)、多枝镰孢(F.reticulatum)、粉红镰孢(F.roseum)、接骨木镰孢(F.sambucinum)、肤色镰孢(F.sarcochroum)、硫色镰孢(F.sulphureum)、F.trichothecioides或尖镰孢(F.oxysporum);腐质霉属(Humicola),如H.insolens或H.lanuginose;毛霉属(Mucor),如米黑毛霉(M.miehei);毁丝霉属(Myceliophthora),如M.thermophilum;脉孢霉属(Neurospora),如粗糙脉孢霉(N.crassa);青霉属(Penicillium),如产紫青霉(P.purpurogenum);梭孢壳属(Thielavia),如T.terrestris;Tolypocladium;或木霉属(Trichoderma),如T.harzianum、康宁木霉(T.koningii)、T.longibrachiatum、T.reesei或绿色木霉(T.viride),或者其有性型或同物异名。利用曲霉属菌种表达蛋白质可参见如文献EP272277、EP230023所述。
昆虫细胞的实例包括鳞翅目(Lepidoptera)细胞系,如秋粘虫(spodoptera frugiperda)细胞或粉纹夜蛾(Trichoplusiani)细胞(参阅US5,077,214)。培养条件可适宜地如WO89/01029或WO89/01028所述。可按如下文献所述进行昆虫细胞的转化和异源多肽的生产:US4745051;US4775624;US4879236;US5155037;US5162222;EP397485。
哺乳动物细胞的实例包括中国仓鼠卵巢(CHO)细胞、HeLa细胞、幼仓鼠肾(BHK)细胞、COS细胞或可获得自如美国典型培养物保藏中心等机构的其它永生化细胞系。转染哺乳动物细胞并表达引入该细胞的DNA序列的方法参阅以下文献:Kaufman和Sharp,J.Mol.Biol.159(1982),601-621;Southern和Berg,J.Mol.Appl.Genet.1(1982),327-341;Loyter等,Proc.Natl.Acad.Sci.USA 79(1982),422-426;Wigler等,Cell 14(1978),725;Corsaro和Pearson,Somatic CellGenetics 7(1981),603;Ausubel等,Current Protocols in MolecularBiology,John Wiley and Sons,Inc.,New York,1987,Hawley-Nelson等,Focus 15(1993),73;Ciccarone等,Focus 15(1993),80;Graham和van der Eb,Virology 52(1973),456;和Neumann等,EMBO J.1(1982),841-845。可以用Graham和Van der Eb的磷酸钙沉淀法(1978,Virology 52:546)通过直接摄取转染哺乳动物细胞。
表达和分离蛋白质的方法
为了表达本发明的酶,通常在允许所需分子产生的条件下将用含有编码本发明酶的核酸序列的载体所转化或转染的上述宿主细胞培养于适当的营养培养基中,然后从细胞或培养液中回收这些分子。
用于培养宿主细胞的培养基可以是适于宿主细胞生长的任何常规培养基,如含适当补充物的基本或复杂培养基。适当的培养基可获自供应商或可以按已公布的配方制备(如,参阅美国典型培养物保藏中心的目录)。培养基也可以用本领域已知的方法制备(参阅,如,有关细菌和酵母的文献;Bennett,J.W.和LaSure,L编辑,《More GeneManipulations in Fungi》,Academic Press,CA,1991)。
如果本发明的酶分泌至营养培养基中,它们可以直接从培养基中回收。如果它们不被分泌,则可以从细胞裂解物中回收。本发明的酶可以用常规方法回收自培养基,包括通过离心或过滤从培养基中分离宿主细胞,用硫酸铵等盐沉淀上清液或滤液中的蛋白质性组分,用各种层析方法进行纯化,如,离子交换层析法、凝胶过滤层析法、亲和层析等等,具体方法取决于目的酶。
本发明的酶可以用本领域已知对这些蛋白质特异的方法进行检测。这些检测方法包括特异抗体的使用、产物的形成或底物的消失。例如,酶测定法可以用于测定分子的活性。用于测定各种活性的方法为本领域所公知。
本发明的酶可以用本领域已知的多种方法进行纯化,包括(但不限于)层析法(如离子交换、亲和、疏水、层析聚焦和大小排阻)、电泳方法(如制备型等电聚焦(IEF))、差异溶解性(如硫酸铵沉淀)或提取(参阅如,《Protein Purification》,J-C Janson和Lars Ryden编,VCH Publishers,New York,1989)。
当含有编码本发明酶的DNA序列的表达载体被转化/转染入异源宿主细胞后,可以实现该酶的异源重组生产。使用异源宿主细胞的优点是,可以产生高度纯化的酶组合物,其特征是不含有同源杂质(当蛋白质或肽表达于同源宿主细胞中时常常存在这些同源杂质)。在本文中,同源杂质指来源于本发明酶最初来自的同源细胞的任何杂质(如,除了本发明酶之外的其它多肽)。
洗涤剂应用
本发明的酶可以添加到洗涤剂组合物中并成为其组分。
例如,本发明的洗涤剂组合物可以制成用于手洗或机洗的洗涤剂组合物,包括适用于预处理污染织物的洗涤添加剂组合物和漂洗添加的纤维软化剂组合物,或制成用于清洁普通家具硬表面的洗涤剂组合物,或被制成用于手洗或机洗的洗盘操作法。
在具体的方面,本发明提供包含本发明的枯草杆菌酶的洗涤添加剂。所述的洗涤添加剂和洗涤剂组合物可以包含一种或多种其它的酶如蛋白酶、脂肪酶、角质酶、淀粉酶、糖酶、纤维素酶、果胶酶、甘露聚糖酶、阿拉伯糖酶、半乳糖酶、木聚糖酶、氧化酶(例如漆酶和/或过氧化物酶)。
一般来说,所选择的酶的特性应当与所选择的洗涤剂相容(即最适pH、与其它酶或非酶成分具相容性等),且所述的酶应以有效剂量存在。
蛋白酶:合适的蛋白酶包括动物、植物、微生物来源的蛋白酶。优选来源于微生物的蛋白酶。也包括经化学修饰或蛋白质改造的突变体。所述的蛋白酶可以是丝氨酸蛋白酶或金属蛋白酶,优选碱性微生物蛋白酶或胰蛋白酶样蛋白酶。碱性蛋白酶的实例为枯草菌素,特别是来自芽孢杆菌的枯草菌素,例如,枯草菌素Novo、枯草菌素Carlsberg、枯草菌素309、枯草菌素147和枯草菌素168(描述于WO89/06279)。胰蛋白酶样蛋白酶的实例为胰蛋白酶(例如来自猪或牛的)和如WO89/06270和WO 94/25583中所述的镰孢霉属的蛋白酶。
有用的蛋白酶的实例是如WO 92/19729,WO 98/20115,WO98/20116和WO 98/34946所描述的变体,特别是在一个或多个以下位置发生替换的变体:27,36,57,76,87,97,101,104,120,123,167,170,194,206,218,222,224,235和274。
优选的市售的蛋白酶包括Alcalase_、Savinase_、Primase_、Duralase_、Esperase_、Ovozyme_和Kannase_(Novozymes A/S)、MaxataseTM、MaxacalTM、MaxapemTM、ProperaseTM、PurafectTM、PurafectOxPTM、FN2TM FN3TM和FN4TM(Genencor International Inc.)。
脂肪酶:合适的脂肪酶包括那些来源于细菌或真菌的脂肪酶。也包括经化学修饰或蛋白质改造的突变体。有用的脂肪酶的实例包括如EP258 068和EP 305 216中所公开的来自腐质霉(Humicola)属(与Thermomyces同物异名),例如来自如EP258068和EP305216中所述的H.lanuginosa(T.lanuginosus)的脂肪酶或如WO 96/13580中所公开的来自H.Insolens的脂肪酶,假单胞菌脂肪酶,例如来自产碱假单胞菌(P.Alcaligenes)或类产碱假单胞菌(P.Pseudoalcaligenes)(EP 218272),洋葱假单胞菌(P.Cepacia)(EP 331 376),施氏假单胞菌(P.stutzeri)(GB 1,372,034),荧光假单胞菌(P.Fluorescens),假单胞菌菌株SD 705(WO 95/06720和WO 96/27002),P.wisconsinensis(WO 96/12012)的脂肪酶;芽孢杆菌脂肪酶,例如来自枯草芽孢杆菌(Dartois等(1993),Biochemica et Biophysica Acta,1131,253-360),嗜热脂肪芽孢杆菌(JP 64/744992)或短小芽孢杆菌(WO 91/16422)。
其它的实例为如WO 92/05249、WO 94/01541、EP 407 225、EP 260105、WO 95/35381、WO 96/00292、WO 95/30744、WO 94/25578、WO95/14783、WO 95/22615、WO 97/04079和WO 97/07202中所公开的脂肪酶变体。
优选的市售的脂肪酶包括Lipex_,Lipolase_和Lipolase Ultra_(Novozymes A/S)。
淀粉酶:合适的淀粉酶(α和/或β)包括那些来源于细菌或真菌的淀粉酶。也包括经化学修饰或蛋白质改造的突变体。淀粉酶包括例如来源于芽孢杆菌的α-淀粉酶,例如来自地衣芽孢杆菌的特定菌株,详细描述参见GB 1,296,839。
有用的淀粉酶的实例是如WO 94/02597、WO 94/18314、WO96/23873和WO 97/43424中所描述的变体,尤其是那些在一个或多个下列位置发生替换的变体:15,23,105,106,124,128,133,154,156,181,188,190,197,202,208,209,243,264,304,305,391,408和444。
市售的淀粉酶是DuramylTM,TermamylTM,FungamylTM和BANTM(Novozymes A/S),RapidaseTM和PurastarTM(来自GenencorInternational Inc.)。
纤维素酶:合适的纤维素酶包括来源于细菌或真菌的纤维素酶。也包括经化学修饰或蛋白质改造的突变体。合适的纤维素酶包括来自芽孢杆菌属、假单胞菌属、腐质霉属、镰孢霉属、草根霉属(Thielavia)、枝顶孢霉属(Acremonium)的纤维素酶,例如在US 4,435,307,US5,648,263,US 5,691,178,US 5,776,757和WO 89/09259中公开的Humicola insolens、嗜热毁丝霉(Myceliophthora thermophila)和尖孢镰孢(Fusarium oxysporum)产生的真菌纤维素酶。
特别合适的纤维素酶是具有颜色保护优点的碱性或中性纤维素酶。这样的纤维素酶的实例为如EP 0 495 257、EP 0 531 372、WO 96/11262、WO 96/29397、WO 98/08940中所公开的纤维素酶。其它的实例为如那些在WO 94/07998、EP 0 531 315、US 5,457,046、US 5,686,593、US5,763,254、WO 95/24471、WO 98/12307和PCT/DK98/00299中所公开的纤维素酶变体。
市售的纤维素酶包括CelluzymeTM和CarezymeTM(NovozymesA/S),ClazinaseTM和Puradax HATM(Genencor International Inc.)和KAC-500(B)TM(Kao Corporation)。
过氧化物酶/氧化酶:合适的过氧化物酶/氧化酶包括那些来源于植物、细菌或真菌的过氧化物酶/氧化酶。也包括化学修饰或蛋白质改造的突变体。有用的过氧化物酶的实例包括如WO 93/24618,WO 95/10602和WO 98/15257中所述的来自鬼伞属(Coprinus)(例如来自灰盖鬼伞(C.cinereus))的过氧化物酶及其变体。
市售的过氧化物酶包括GuardzymeTM(Novozymes A/S)。
可以通过添加含一种或多种酶的独立添加剂,或通过添加含所有这些酶的组合添加剂而使洗涤剂酶包含于洗涤剂组合物中。本发明的洗涤剂添加剂(即独立添加剂或组合添加剂)可以制成例如颗粒状、液体、浆状等等。优选的洗涤剂添加剂形式为颗粒状(特别是无粉尘颗粒)、液体(特别是稳定的液体)或浆。
无粉尘颗粒可依照例如US4,106,991和4,661,452所述进行生产并可任选地用本领域已知的方法加包衣。蜡状包衣材料的实例是平均分子量为1000到20000的聚(环氧乙烷)产物(聚乙二醇,PEG)、含有16到50个环氧乙烷单位的乙氧基化的壬基酚、乙氧基脂肪醇(其中醇含12到20个碳原子且其中存在15到80个环氧乙烷单位)脂肪醇;脂肪酸;和脂肪酸的单、二和三甘油酯。GB 1483591中给出了适合于通过流化床技术应用的成膜包衣材料的实例。液体酶制剂可以依照现成的方法通过例如添加多元醇如丙二醇、糖或糖醇、乳酸或硼酸得以稳定。受保护的酶可依照EP 238,216中所公开的方法进行制备。
本发明的洗涤剂组合物可以是任何便利的形式,例如棒状、片状、粉末、颗粒、粘团或液体。液体洗涤剂可以是含水的,一般含高达70%的水和0-30%的有机溶剂,或不含水的。
所述的洗涤剂组合物包含一种或多种表面活性剂,它们可以是非离子(包括半极性的)和/或阴离子和/或阳离子和/或两性离子表面活性剂。所述的表面活性剂一般占到0.1%到60%的重量水平。
当包含在所述洗涤剂中时,通常包含约1%到约40%的阴离子表面活性剂,如直链烷基苯磺酸盐、α-烯属磺酸盐、硫酸烷基酯(硫酸脂肪醇酯)、乙氧基硫酸醇酯、仲链烷磺酸酯、α-磺基脂肪酸甲酯、烷基-或链烯基琥珀酸或肥皂。
当包含在所述洗涤剂中时,通常含有约0.2%到约40%的非离子表面活性剂,例如乙氧基化醇、乙氧基化壬基酚、烷基多苷、烷基二甲基胺氧化物、乙氧基化脂肪酸单乙醇酰胺、脂肪酸单乙醇酰胺、多羟基烷基脂肪酸酰胺或葡糖胺的N-酰基N-烷基衍生物(“葡糖酰胺”)。
所述的洗涤剂可以包含0-65%的洗涤剂增洁剂或络合剂,例如沸石、二磷酸盐、三磷酸盐、磷酸盐、碳酸盐、柠檬酸盐、次氮基三乙酸、乙二胺四乙酸、二亚乙基三胺五乙酸、烷基-或链烯基琥珀酸、可溶性硅酸盐或层状硅酸盐(例如购自Hoechst的SKS-6)。
所述的洗涤剂还可以包含一种或多种聚合物。实例为羧甲基纤维素、聚(乙烯吡咯烷酮)、聚(乙二醇)、聚(乙烯醇)、聚(乙烯基吡啶-N-氧化物)、聚(乙烯基咪唑)、聚羧酸如聚丙烯酸、马来酸/丙烯酸共聚物和甲基丙烯酸月桂醇酯/丙烯酸共聚物。
所述的洗涤剂还可以含有可以包含H2O2来源的漂白体系,如可以与四乙酰基乙二胺或壬酰氧基苯磺酸盐之类的形成过酸的漂白活化剂结合的过硼酸盐或过碳酸盐。另外,所述的漂白体系可以包含例如酰胺、二酰亚胺或砜类的过氧酸。
本发明的洗涤剂组合物中的酶可以通过诸如以下的常规稳定剂稳定:多元醇(如丙二醇或丙三醇)、糖或糖醇、乳酸、硼酸或硼酸衍生物(如芳香硼酸酯或苯基硼酸衍生物,如4-甲酰基苯基硼酸),且所述的组合物也可以按如WO 92/19709和WO 92/19708中所述配制。
所述的洗涤剂还可以包含其它的常规洗涤剂成分,例如织物调理剂,包括黏土、增泡剂、泡沫抑制剂、抗腐蚀剂、尘粒悬浮剂、抗尘粒再沉淀剂、染料、杀菌剂、荧光增白剂、助溶剂、失泽抑制剂(tarnishinhibitor)或香料。
目前认为在所述洗涤剂组合物中任何酶,特别是本发明的酶可以以相当于每升洗涤液中具有0.01-200mg酶蛋白质,优选每升洗涤液0.05-50mg酶蛋白质,特别优选每升洗涤液中具有0.1-10mg酶蛋白质的量加入。
此外,本发明的酶可以添加到WO 97/07202所公开的洗涤剂制剂中,该文献引入本文作为参考。
材料和方法
织物
标准织物片得自瑞士EMPA St.Gallen,Lerchfeldstrasse 5,CH-9014 St.Gallen。尤其是类型EMPA116(具有血液、乳液和墨水污渍的棉织物)和EMPA117(具有血液、乳液和墨水污渍的聚酯/棉织物)。
产生枯草杆菌酶变体的方法
本发明提供了产生符合本发明的分离酶的方法,其中在允许酶产生的条件下培养转化了编码该酶DNA序列的合适的宿主细胞,并从培养物中回收产生的酶。
当将含有编码酶的DNA序列的表达载体转化入异源宿主细胞中时,即可使本发明的酶异源重组产生。由此可以产生以不含同源杂质为特征的高度纯化的枯草杆菌酶组合物。
用于培养转化的宿主细胞的培养基可以是任何适合于目的宿主细胞生长的常规培养基。所表达的枯草杆菌酶可便利地分泌到培养基中并可以通过已知的方法回收,所述方法包括通过离心或过滤从培养基中分离细胞,再利用盐(如硫酸铵)沉淀培养基中的蛋白质组分,接着进行层析,如离子交换层析、亲和层析等。
实施例1
Savinase变体文库的构建
已经合成了基于枯草杆菌酶位置V28、I35、T71、I72、A73、M175和T224(BPN’编号)的文库。文库专门含有了TY145提示的改变并涵盖了寡肽中引入的突变V28I、A、L;I35V、A、L;T71S;I72A、G、v;A73L、G;M175V、A;T224S、A,其中一些为搀杂的突变。可以按本文18页所述计算以下实施例中使用的来自单个氨基酸残基所需要搀杂的核苷酸碱基搀杂。
在附带的序列列表中,给予以下搀杂的核苷酸以WIPO标准ST25所推荐的核苷酸标志。
构建的寡肽引物列表如下。引物按发生修饰的位置命名,因此28-35-CN可以在位置28和35发生改变,71-72-73-NC可以在位置71、72和73发生改变,等等。
28-35-CN,SEQ ID NO:7
5’-TAG ATC TGG ATG AGT GGA(50%T/50%A)(80%A/10%G/10%C)(75%T/25%C)CCC
TGT ATC GAG GAC AGC(75%A/25%T)(90%A/10%G)(80%C/10%T/10%G)TTT TAC ACC
AGA ACC TGT-3’
28-35-NC,SEQ ID NO:8
5’-TCC ACT CAT CCA GAT CTA-3’
(I)71-72-73-CN,SEQ ID NO:9
5’-AAT CGA ATT GTT TAA AGC AGC(65%T/35%A)(80%A/10%C/10%G)(75%T/25%C)
(90%C/10%T)G(90%T/10%A)CCC GGC CAC ATG CGT GCC-3’
(II)71-72-73-CN,SEQ ID NO:10
5’-AAT CGA ATT GTT TAA AGC AAG(65%T/35%A)(80%A/10%C/10%G)(75%T/25%C)
(90%C/10%T)G(90%T/10%A)CCC GGC CAC ATG CGT GCC-3’
(III)71-72-73-CN,SEQ ID NO:11
5’-AAT CGA ATT GTT TAA AGC GCC(65%T/35%A)(80%A/10%C/10%G)(75%T/25%C)
(90%C/10%T)G(90%T/10%A)CCC GGC CAC ATG CGT GCC-3’
71-72-73-NC,SEQ ID NO:12
5’GCT TTA AAC AAT TCG ATT 3’
139,SEQ ID NO:13
5’-GAT TAA CGC GTT GCC GCT TCT GCG-3’
(I)175-CN(90%),SEQ ID NO:14
5’-ATC AGT AGC TCC GAC TGC CA(90%T/10%C)TGC GTT CGC ATA GCG CGC-3’
(II)175-CN(10%),SEQ ID NO:15
5’-ATC AGT AGC TCC GAC TGC CGC TGC GTT CGC ATA GCG CGC-3’
175-NC,SEQ ID NO:16
5’-GCA GTC GGA GCT ACT GAT-3’
224-CN,SEQ ID NO:17
5’-CGC ACC TGC AAC ATG AGG CG(80%T/10%C/10%A)AGC CAT CGA TGT ACC GTT-
3’
224-NC,SEQ ID NO:18
5’-CCT CAT GTT GCA GGT GCG-3’
317,SEQ ID NO:19
5’-TGG CGC AAT CGG TAC CAT GGG G-3’
在标准PCR条件下(Sambrook等,《Molecular Cloning:ALaboratory Manual》,第二版,Cold Spring Harbor,1989)使用Savinase基因作为5个单独的PCR反应的模板,其中寡聚物按如下组合:317和28-35-CN、28-35-NC和71-72-73-CN(80%(I)71-72-73-CN,10%(II)71-72-73-CN and 10%(III)71-72-73-CN的混合物)、71-72-73-NC和175-CN(90%(I)175-CN和10%(II)175-CN的混合物)、175-NC和224-CN、224-NC和139,得到的PCR产物分别为125bp、126bp、312bp、165bp和158bp。
通过将5个PCR产物等摩尔量混合的一个额外的PCR反应装配了文库。因此文库包含了在一个或多个所提及位置发生改变的为数众多的不同Savinase变体。采用PTC-200 DNA Engine(MJ Research,Watertown,MA)进行PCR反应并设置如下循环参数:1个94℃ 2分钟循环,接着25个94℃ 30秒、55℃ 30秒、68℃ 1分钟的循环,及1个68℃ 2分钟的循环。通过PCR多聚化(Shafikhani等,1997)将文库克隆到Savinase表达载体psx222中并转化进枯草杆菌宿主细胞进行表达。接着可以从文库中分离出纯化的、特征性的Savinase变体。
同样的,可以应用类似程序将来源于BPN’样枯草杆菌酶的特性转移到TY145样枯草杆菌酶中
实施例2
来自TY145的区域向BPN’枯草杆菌酶的转移
已选择了将下文提到的TY145中的高活动区从TY145转移到Savinase中。删除Savinase区域(BPN’编号)后插入TY145区域(SEQID NO:1)以代替。另外,可以选择区域在嗜冷TA41/TA39和BPN’型蛋白酶样Savinase间转移,或从TA39/TA41到TY145型非嗜冷枯草杆菌酶。
片段I
TY145 SAKDSLIASAVD,位置144-155(SEQ ID NO:22)
Savinase PSPSATLEQAVN,位置129-140(SEQ ID NO:23)
片段II
TY145 AGNSGSGSNTIGFPGGLV,位置168-185(SEQ ID NO:24)
Savinase SGNSGAGSISYPARYA,位置153-172(SEQ ID NO:25)
片段IV
TY145 ASVESTWYTGGYNTIS,位置233-248(SEQ ID NO:26)
Savinase VNVQSTYPGSTYASLN,位置203-218(SEQ ID NO:27)
通过鉴定脱脂奶粉平板上亮区的形成观察到,分别接受TY145片段II(杂合体II)、IV(杂合体IV)或I+II(杂合体I+II)而被修饰的Savinase表现出枯草杆菌酶活性。
实施例3
来自S39和S41的区域向BPN’枯草杆菌酶的转移
已选择了将下文提到的TA39枯草杆菌酶S39和TA41枯草杆菌酶S41中的高活动区转移到Savinase,其高活动区通过前述同源性建立程序鉴定。删除Savinase区域(BPN’编号)后插入S39区域或S41区域以代替。下文中S39和S41区域根据图1编号。另外可以选择区域在嗜冷TA41/TA39和TA145型非嗜冷枯草杆菌酶间转移。使用Savinase变体V194S作为S39片段II的受体。
片段I
S39 MSLGSSG,位置137-143(SEQ ID NO:28)
Savinase2 LSLGSPS,位置124-130(SEQ ID NO:29)
片段II
S39 MSLGSSGESSLI,位置137-148(SEQ IDNO:30)
Savinase变体V104S LSLGSPSPSATL,位置124-135(SEQ IDNO:31)
片段III
S39 NNSSITQT,位置15-22(SEQ ID NO:32)
Savinase VQAPAAHN,位置11-18(SEQ ID NO:33)
片段IV
S39 TVGTTYTN,位置55-62(SEQ ID NO:34)
Savinase2 VPG*EPST,位置51*-58(SEQ ID NO:35)
片段V
S39 RQ,位置68-69
Savinase GN,位置61-62
片段VI
S39 SGESSLI,位置142-148(SEQ ID NO:36)
Savinase PSPSATL,位置129-135(SEQ ID NO:37)
片段VII
S39 WFDGGYATI,位置237-245(SEQ ID NO:38)
Savinase YPGSTYASL,位置209-217(SEQ ID NO:39)
观察到通过分别接受来源于S39的片段I或II而被修饰的Savinase变体对底物suc-AAPF-pNA(Suc-Ala-Ala-Pro-Phe-pNA)有枯草杆菌酶活性。通过温度轮廓试验测定枯草杆菌酶活性,其中每5摄氏度测定比活性,即针对前述底物的每分钟每毫克酶的底物微摩尔数。在pH9的Tris碱缓冲液中进行测量。
为测量在suc-AAPF-pNA中的枯草杆菌酶活性:将100μL 0.1M Tris中的1.56mM的Suc-Ala-Ala-Pro-Phe-pNA加入100μL Tris碱、pH9.0缓冲液和20μL酶中。降解产物pNA(对硝基酚)的显色通过酶标仪在405nm处1分钟内的初速度测定。
含有片段I替换的Savinase变体与Savinase相比对suc-AAPF-pNA具有较弱的比活性,而含有片段II替换的Savinase变体对suc-AAPF-pNA具有比Savinase高2倍以上的比活性。在AMSA试验中(如本文实施例5所述进行)表明,含有片段II替换的Savinase变体与Savinase相比,洗涤性能得到了保持。
另外,用下列来源于S39的片段组合构建了4个Savinase变体:
片段III、V和VII;片段III和V;片段III、V、VI以及片段III和IV。全部4个Savinase变体在脱脂乳平板上表现枯草杆菌酶活性。
建议转移至Savinase的S41枯草杆菌酶片段为:
片段VIII
S41 TVGTNFTD,位置55-62(SEQ ID NO:40)
Savinase VPG*EPST,位置51-58(SEQ ID NO:41)
片段IX
S41 NGGTGS,位置82-87(SEQ ID NO:42)
Savinase ALNNSI,位置74-79(SEQ ID NO:43)
片段X
S41 DDGSGYA,位置106-112(SEQ ID NO:44)
Savinase ASGSGSV,位置98-104(SEQ ID NO:45)
片段XI
S41 WAQSPAA,位置263-269(SEQ ID NO:46)
Savinase KQKNPSW,位置235-241(SEQ ID NO:47)
用S41的下列片段构建了4个Savinase变体:
片段X;片段IX and X;片段VIII and X;以及片段X and XI。全部4个Savinase变体在脱脂乳平板上表现枯草杆菌酶活性。
按在本文实施例5中所述对具有片段X及片段X和XI的变体进行了AMSA洗涤试验。
在以下指定的实验条件下进行试验:
洗涤剂基础 | Omo Acao |
洗涤剂剂量 | 2.5g/l |
受试溶液体积 | 160ul |
pH | 用NaHCO3调节至10-10.5 |
洗涤时间 | 14分钟 |
温度 | 15℃ |
水硬度 | 9°dH |
受试溶液中的酶浓度 | 5nM、10nM和30nM |
受试材料 | EMPA 117 |
具有片段X及片段X和XI的Savinase变体的洗涤性能分值(描述于本文实施例5)为S(1),该分值表示与Savinase相比更高的洗涤性能。
实施例4
纯化和酶浓度的评估
发酵后使用疏水电荷感应层析(HCIC)和接下来使用真空过滤来纯化枯草菌素变体。为了捕获酶,HCIC使用的纤维素基质结合有4-巯基-乙基-吡啶(4-MEP)。
将大小为80-100μm的纤维素基质珠与含酵母提取物的培养基和可分泌枯草菌素变体的经转化的枯草芽孢杆菌混合,并在Unifilter_微孔板中于pH9.5孵育。
由于4-MEP在pH>7时疏水,且枯草菌素变体在pH9.5时疏水,所以所分泌的酶和在珠上的4-MEP之间存在疏水相互作用。孵育后,通过真空过滤除去培养基和细胞碎片,而珠子和酶位于滤器上。
为了将酶自珠子上洗脱,通过用洗脱缓冲液(pH5)洗涤滤器而降低pH。由此将酶与珠子分离,并可从缓冲液中回收。
经纯化的枯草菌素变体的浓度通过活性部位滴定(AST)评估。将经纯化酶与不同浓度的高亲和力抑制剂CI-2A孵育,以抑制不同量的活性位点。所述蛋白酶与抑制剂以1∶1的比例相互结合,因此酶浓度可直接与抑制剂浓度相关,在抑制剂浓度下,所有的蛋白酶是失活的。为了测定残余蛋白酶活性,在与抑制剂孵育后加入底物(Tris/HCl缓冲液中的0.6mMSuc-Ala-Ala-Pro-Phe-pNA),接下来的4分钟降解产物pNA(对硝基酚)的显色使用酶标仪于405nm定时测定。
实施例5
含有修饰酶的洗涤剂组合物的洗涤性能
在低洗涤温度下测试含有本发明的酶杂合体或酶变体的洗涤剂组合物的洗涤性能。
使用两种不同试验测试了实施例2的Savinase变体杂合体IV的洗涤性能:微升尺度试验(microlitre scale assay)(AMSA)和毫升尺度试验(millilitre scale assay)(微型洗涤)。
AMSA
使用自动机械应力试验(AMSA)测试本发明的酶变体。使用AMSA试验可检查大量的小体积酶洗涤剂溶液的洗涤性能。所述AMSA板具有许多装受试溶液的槽和将织物小条紧紧挤压以使之在槽穴中洗涤的盖子。在洗涤期间,将板、受试溶液、织物和盖子剧烈摇动,以使受试溶液与织物接触并施加机械应力。进一步的描述参阅WO 02/42740,特别是23-24页“特定方法的实施方案”段落。
实验在以下指定的实验条件下进行:
洗涤剂基础 | Omo Acao |
洗涤剂剂量 | 1.5g/l |
受试溶液体积 | 160ul |
pH | 用NaHCO3调节至10-10.5 |
洗涤时间 | 12分钟 |
温度 | 20℃ |
水硬度 | 9°dH |
受试溶液中的酶浓度 | 5nM、10nM和30nM |
受试材料 | EMPA 117 |
洗涤后织物用自来水冲洗并晾干
以用特定酶变体洗涤的织物样本颜色的亮度来测定酶变体的洗涤性能。亮度可表示为当用白色光照射时自织物样本反射的光强度。当织物有污渍时,反射光的强度较干净的织物低。因此可用反射光的强度测定酶变体的洗涤性能。
颜色测量用专门的平台扫描仪(PFU DL2400pro)进行,该仪器用于捕捉经洗涤织物样本的图像。使用分辨率200dpi和24位输出色深(colordept)进行扫描。为了获得准确的结果,常用Kodak reflective IT8 target校正扫描仪。
为了从扫描图像获得光强度的值,使用了专门设计的应用软件(Novozymes Color Vector Analyzer)。该程序自图像获取24位象素值,并将它们转化为红、绿和兰的值(RGB)。通过将RGB值作为向量相加而得到向量长度来计算强度值(Int):
变体的洗涤性能(P)根据下式计算:
P=Int(v)-Int(r)
其中Int(v)为用酶变体洗涤的织物表面的光强度值,且Int(r)为用参照酶枯草菌素309(BLSAVI)洗涤的织物表面的光强度值。
杂合体IV的AMSA洗涤结果为按如下定义的性能分值S(2):
性能分值(S)如下概括了受试酶的性能(P):
S(2)表明在所有三个酶浓度(5、10和30nM)下变体表现出优于参照物,且
S(1)表明在一个或两个浓度下变体表现出优于参照物。
微型洗涤试验
在以下条件下进行毫升尺度洗涤性能试验:
洗涤剂基础 | Omo Acao洗涤剂粉末 |
洗涤剂剂量 | 1.5g/l |
pH | 按当前洗涤剂,未调整 |
洗涤时间 | 14分钟 |
温度 | 20℃ |
水硬度 | 通过在milli-Q水中加入CaCl2*2H2O;MgCl2*6H2O;NaHCO3(Ca2+∶Mg2+∶HCO3-=2∶1∶6)调整至9°dH |
酶 | 杂合体IV,Savinase |
酶浓度 | 5nM,10nM |
测试系统 | 125ml玻璃烧杯。织物浸泡于受试溶液中。持 |
续振荡,每分钟50次。 | |
织物/体积 | 50ml受试溶液中1个织物片(13×3cm) |
受试材料 | EMPA 117织物样本 |
洗涤后使用Zeiss MCS 521 VIS分光光度计在460nm处测定受试材料的清除度(remission)。测定按照制造商的流程进行。
如表1所示,20℃下在Omo Acao中用Savinase变体杂合体IV洗涤的织物有比用亲本洗涤的织物具有更高的清除度。该结果表明变体在低温下具有比亲本Savinase更好的洗涤性能。
表1.Omo Acao中5nM和10nM酶剂量枯草杆菌酶变体的洗涤性能结果
酶 | 清除度,5nM酶 | 清除度,10nM酶 |
空白(无酶) | 12,0 | 12,3 |
Savinase | 15,8 | 17,4 |
Hybrid IV | 17,0 | 18,3 |
从表1中可以得出结论,本发明的修饰酶表现出洗涤性能上的改进。
实施例6
在低温下使用如本文实施例5中所述的自动机械应力试验(AMSA)测试含有本发明酶变体的洗涤剂组合物的洗涤性能。
表2.枯草杆菌酶变体的AMSA洗涤结果
酶变体 | 性能分值 |
V28I+*98aD+T224S | 2 |
*98aS+P131F+M175V+T224A | 1 |
附录1
REMARK 3 优化
REMARK 3 程序:REFMAC 5.0
REMARK 3 作者:MURSHUDOV,VAGIN,DODSON
REMARK 3
REMARK 3 优化目标:最大相似度
REMARK 3
REMARK 3 优化中使用的数据
REMARK 3 分辨率范围高(埃):1.80
REMARK 3 分辨率范围低(埃):56.80
REMARK 3 数据截断(SIGMA(F)):无
REMARK 3 范围完整性(%):99.88
REMARK 3 反射数:38045
REMARK 3
REMARK 3 优化使用数据的FIT
REMARK 3 交叉验证方法:全部
REMARK 3 自由R值试验集选择:随机
REMARK 3 R值(工作+试验集):0.15648
REMARK 3 R值(工作集):0.15487
REMARK 3 自由R值:0.18707
REMARK 3 自由R值试验集尺寸(%):5.0
REMARK 3 自由R值试验集数:2009
REMARK 3
REMARK 3 最高分辨率面元中的FIT
REMARK 3 使用的面元总数:20
REMARK 3 面元分辨率范围高:1.796
REMARK 3 面元分辨率范围低:1.842
REMARK 3 面元反射(工作集):2738
REMARK 3 面元R值(工作集):0.191
REMARK 3 面元自由R值集合数:138
REMARK 3 面元自由R值:0.234
REMARK 3
REMARK 3 优化中使用的非氢原子数.
REMARK 3 全部原子:3156
REMARK 3
REMARK 3 B值.
REMARK 3 从WILSON曲线(A**2):无
REMARK 3 平均B值(总体,A**2):14.804
REMARK 3 总体各向异性B值.
REMARK 3 B11(A**2):0.28
REMARK 3 B22(A**2):-0.86
REMARK 3 B33(A**2):0.58
REMARK 3 B12(A**2):0.00
REMARK 3 B13(A**2):0.00
REMARK 3 B23(A**2):0.00
REMARK 3
REMARK 3 预计总体坐标误差.
REMARK 3 基于R值的ESU (A):0.100
REMARK 3 基于自由R值的ESU (A):0.098
REMARK 3 基于最大相似性的ESU (A):0.093
REMARK 3 基于最大相似性的B值ESU (A**2):2.910
REMARK 3
REMARK 3 相关系数
REMARK 3 相关系数FO-FC:0.963
REMARK 3 相关系数FO-FC释放:0.952
REMARK 3
REMARK 3 RMS与理想值的偏差 数目 RMS 权重
REMARK 3 优化原子的键长 (A):2798;0.021;0.021
REMARK 3 其他键长 (A):2500;0.001;0.020
REMARK 3 优化原子的键角 (度):3805;1.859;1.943
REMARK 3 其他键角 (度):5821;0.854;3.000
REMARK 3 扭转角,周期1 (度):372;5.125;3.000
REMARK 3 扭转角,周期3 (度):462;16.877;15.000
REMARK 3 手性中心抑制 (A**3):437;0.119;0.200
REMARK 3 优化原子一般平面 (A):3201;0.009;0.020
REMARK 3 其他一般平面 (A):535;0.004;0.020
REMARK 3 优化原子的非键接触 (A):610;0.228;0.300
REMARK 3 其他非键接触 (A):2548;0.203;0.300
REMARK 3 优化原子的氢键(X…Y) (A):374;0.184;0.500
REMARK 3 其他氢键(X…Y) (A):3;0.279;0.500
REMARK 3 优化原子的潜在金属离子 (A):16;0.119;0.500
REMARK 3 优化原子的对称性VDW (A):7;0.127;0.300
REMARK 3 其他对称性VDW (A):27;0.152;0.300
REMARK 3 优化原子氢键对称性 (A):37;0.278;0.500
REMARK 3
REMARK 3 各向同性热因子限制 数目 RMS 权重
REMARK 3 优化原子主链键 (A**2):1840;1.131;1.500
REMARK 3 优化原子主链角 (A**2):2941;1.781;2.000
REMARK 3 优化原子侧链键 (A**2):958;2.873;3.000
REMARK 3 优化原子侧链角 (A**2):864;4.300;4.500
REMARK 3
REMARK 3 NCS限制统计
REMARK 3 NCS组的数目:无
REMARK 3
REMARK 3
REMARK 3 TLS细节
REMARK 3 TLS组的数目:NULL
REMARK 3
REMARK 3
REMARK 3 大量溶剂构型
REMARK 3 使用方法:有掩码的BABINET模型
REMARK 3 计算掩码的参数
REMARK 3 VDW探针半径:1.40
REMARK 3 离子探针半径:0.80
REMARK 3 收缩半径:0.80
REMARK 3
REMARK 3 其他优化注意事项:
REMARK 3 氢加入到骑乘位置中
REMARK 3
CISPEP 1GLY A 172 SER A 173 0.00
CISPEP 2PHE A 180 PRO A 181 0.00
SSBOND 1CYS A 52 CYS A 66
CRYST1 58.753 66.838 107.082 90.00 90.00 90.00 P 21 21 21
SCALE1 0.017020 0.000000 0.000000 0.00000
SCALE2 0.000000 0.014962 0.000000 0.00000
SCALE3 0.000000 0.000000 0.009339 0.00000
ATOM 1 N ALA A 1 2.336 20.870 1.027 1.00 27.48 N
ATOM 3 CA ALA A 1 1.951 20.940 2.465 1.00 29.42 C
ATOM 5 CB ALA A 1 2.391 19.637 3.197 1.00 29.45 C
ATOM 9 C ALA A 1 2.665 22.149 3.096 1.00 28.87 C
ATOM 10 O ALA A 1 3.696 22.577 2.627 1.00 30.49 O
ATOM 13 N VAL A 2 2.014 22.747 4.052 1.00 30.31 N
ATOM 15 CA VAL A 2 2.658 23.754 4.877 1.00 30.69 C
ATOM 17 CB VAL A 2 2.068 25.139 4.604 1.00 30.94 C
ATOM 19 CG1 VAL A 2 2.611 25.702 3.252 1.00 32.62 C
ATOM 23 CG2 VAL A 2 0.577 25.086 4.667 1.00 30.84 C
ATOM 27 C VAL A 2 2.494 23.346 6.347 1.00 29.48 C
ATOM 28 O VAL A 2 1.580 22.610 6.743 1.00 29.33 O
ATOM 29 N PRO A 3 3.412 23.788 7.186 1.00 28.10 N
ATOM 30 CA PRO A 3 3.298 23.380 8.581 1.00 27.90 C
ATOM 32 CB PRO A 3 4.645 23.830 9.185 1.00 26.48 C
ATOM 35 CG PRO A 3 5.116 24.998 8.340 1.00 26.57 C
ATOM 38 CD PRO A 3 4.530 24.697 6.933 1.00 27.60 C
ATOM 41 C PRO A 3 2.129 24.112 9.216 1.00 27.01 C
ATOM 42 O PRO A 3 1.602 25.037 8.600 1.00 28.48 O
ATOM 43 N SER A 4 1.767 23.774 10.434 1.00 26.37 N
ATOM 45 CA SER A 4 0.718 24.505 11.159 1.00 25.29 C
ATOM 47 CB SER A 4 0.279 23.780 12.444 1.00 26.52 C
ATOM 50 OG SER A 4 1.173 23.913 13.554 1.00 25.41 O
ATOM 52 C SER A 4 1.105 25.956 11.445 1.00 26.09 C
ATOM 53 O SER A 4 0.212 26.810 11.603 1.00 25.32 O
ATOM 54 N THR A 5 2.415 26.233 11.497 1.00 24.12 N
ATOM 56 CA THR A 5 3.023 27.567 11.741 1.00 22.81 C
ATOM 58 CB THR A 5 3.009 28.007 13.237 1.00 24.21 C
ATOM 60 OG1 THR A 5 3.793 29.191 13.386 1.00 23.29 O
ATOM 62 CG2 THR A 5 3.727 26.999 14.151 1.00 22.71 C
ATOM 66 C THR A 5 4.413 27.436 11.219 1.00 23.10 C
ATOM 67 O THR A 5 5.012 26.322 11.267 1.00 21.48 O
ATOM 68 N GLN A 6 4.959 28.518 10.692 1.00 21.30 N
ATOM 70 CA GLN A 6 6.260 28.438 10.102 1.00 21.50 C
ATOM 72 CB GLN A 6 6.512 29.634 9.209 1.00 22.77 C
ATOM 75 CG GLN A 6 5.626 29.570 7.926 1.00 23.15 C
ATOM 78 CD GLN A 6 5.999 30.579 6.911 1.00 28.40 C
ATOM 79 OE1 GLN A 6 5.356 31.619 6.822 1.00 30.34 O
ATOM 80 NE2 GLN A 6 7.016 30.300 6.133 1.00 24.59 N
ATOM 83 C GLN A 6 7.295 28.389 11.185 1.00 20.24 C
ATOM 84 O GLN A 6 8.438 28.017 10.927 1.00 18.46 O
ATOM 85 N THR A 7 6.870 28.777 12.378 1.00 18.84 N
ATOM 87 CA THR A 7 7.752 28.808 13.565 1.00 19.27 C
ATOM 89 CB THR A 7 8.135 30.238 13.914 1.00 19.55 C
ATOM 91 OG1 THR A 7 6.958 31.041 14.091 1.00 23.00 O
ATOM 93 CG2 THR A 7 8.910 30.878 12.842 1.00 19.61 C
ATOM 97 C THR A 7 7.111 28.128 14.755 1.00 18.28 C
ATOM 98 O THR A 7 6.436 28.735 15.547 1.00 18.57 O
ATOM 99 N PRO A 8 7.288 26.803 14.834 1.00 17.34 N
ATOM 100 CA PRO A 8 6.795 26.000 15.922 1.00 17.79 C
ATOM 102 CB PRO A 8 7.459 24.615 15.659 1.00 17.18 C
ATOM 105 CG PRO A 8 7.556 24.570 14.138 1.00 18.32 C
ATOM 108 CD PRO A 8 7.961 25.984 13.814 1.00 16.59 C
ATOM 111 C PRO A 8 7.162 26.584 17.273 1.00 16.99 C
ATOM 112 O PRO A 8 8.105 27.339 17.369 1.00 18.02 O
ATOM 113 N TRP A 9 6.426 26.203 18.280 1.00 18.21 N
ATOM 115 CA TRP A 9 6.613 26.750 19.611 1.00 17.56 C
ATOM 117 CB TRP A 9 5.723 26.059 20.603 1.00 17.84 C
ATOM 120 CG TRP A 9 6.129 24.806 21.197 1.00 14.36 C
ATOM 121 CD1 TRP A 9 5.772 23.569 20.796 1.00 15.37 C
ATOM 123 NE1 TRP A 9 6.278 22.630 21.658 1.00 15.66 N
ATOM 125 CE2 TRP A 9 7.033 23.276 22.609 1.00 16.83 C
ATOM 126 CD2 TRP A 9 6.952 24.642 22.345 1.00 14.81 C
ATOM 127 CE3 TRP A 9 7.642 25.531 23.186 1.00 14.62 C
ATOM 129 CZ3 TRP A 9 8.362 24.982 24.301 1.00 11.92 C
ATOM 131 CH2 TRP A 9 8.393 23.626 24.526 1.00 15.97 C
ATOM 133 CZ2 TRP A 9 7.757 22.750 23.677 1.00 14.67 C
ATOM 135 C TRP A 9 8.073 26.760 20.083 1.00 18.17 C
ATOM 136 O TRP A 9 8.531 27.737 20.662 1.00 15.91 O
ATOM 137 N GLY A 10 8.780 25.675 19.859 1.00 16.36 N
ATOM 139 CA GLY A 10 10.180 25.618 20.307 1.00 15.48 C
ATOM 142 C GLY A 10 11.108 26.619 19.663 1.00 15.80 C
ATOM 143 O GLY A 10 12.089 27.060 20.254 1.00 14.71 O
ATOM 144 N ILE A 11 10.801 26.939 18.410 1.00 15.18 N
ATOM 146 CA ILE A 11 11.599 27.866 17.642 1.00 15.64 C
ATOM 148 CB ILE A 11 11.303 27.768 16.151 1.00 14.65 C
ATOM 150 CG1 ILE A 11 11.479 26.328 15.653 1.00 15.91 C
ATOM 153 CD1 ILE A 11 12.945 25.811 15.725 1.00 16.96 C
ATOM 157 CG2 ILE A 11 12.204 28.704 15.385 1.00 16.09 C
ATOM 161 C ILE A 11 11.291 29.225 18.193 1.00 15.73 C
ATOM 162 O ILE A 11 12.197 29.995 18.438 1.00 15.02 O
ATOM 163 N LYS A 12 10.005 29.552 18.352 1.00 16.62 N
ATOM 165 CA LYS A 12 9.649 30.832 18.949 1.00 16.28 C
ATOM 167 CB LYS A 12 8.147 30.926 19.078 1.00 17.21 C
ATOM 170 CG LYS A 12 7.419 31.148 17.707 1.00 20.12 C
ATOM 173 CD LYS A 12 5.874 31.303 17.997 1.00 20.50 C
ATOM 176 CE LYS A 12 5.137 31.855 16.795 1.00 28.93 C
ATOM 179 NZ LYS A 12 4.564 30.819 15.858 1.00 19.42 N
ATOM 183 C LYS A 12 10.242 30.956 2O.345 1.00 15.82 C
ATOM 184 O LYS A 12 10.790 32.014 20.745 1.00 15.87 O
ATOM 185 N SER A 13 10.172 29.865 21.075 1.00 13.09 N
ATOM 187 CA SER A 13 10.655 29.893 22.450 1.00 13.64 C
ATOM 189 CB SER A 13 10.284 28.586 23.149 1.00 12.46 C
ATOM 192 OG SER A 13 10.790 28.548 24.491 1.00 14.12 O
ATOM 194 C SER A 13 12.167 30.131 22.519 1.00 12.81 C
ATOM 195 O SER A 13 12.650 30.959 23.323 1.00 11.51 O
ATOM 196 N ILE A 14 12.931 29.371 21.752 1.00 12.90 N
ATOM 198 CA ILE A 14 14.391 29.521 21.839 1.00 13.05 C
ATOM 200 CB ILE A 14 15.108 28.318 21.206 1.00 12.73 C
ATOM 202 CG1 ILE A 14 16.498 28.183 21.810 1.00 13.73 C
ATOM 205 CD1 ILE A 14 17.265 26.959 21.415 1.00 17.32 C
ATOM 209 CG2 ILE A 14 15.161 28.394 19.753 1.00 14.13 C
ATOM 213 C ILE A 14 14.869 30.861 21.299 1.00 14.41 C
ATOM 214 O ILE A 14 15.907 31.367 21.680 1.00 15.23 O
ATOM 215 N TYR A 15 14.094 31.423 20.389 1.00 15.25 N
ATOM 217 CA TYR A 15 14.392 32.753 19.877 1.00 16.87 C
ATOM 219 CB TYR A 15 13.742 32.965 18.490 1.00 15.13 C
ATOM 222 CG TYR A 15 14.683 32.629 17.348 1.00 16.40 C
ATOM 223 CD1 TYR A 15 14.956 31.303 17.008 1.00 14.01 C
ATOM 225 CE1 TYR A 15 15.834 30.998 16.024 1.00 16.36 C
ATOM 227 CZ TYR A 15 16.453 31.993 15.321 1.00 16.82 C
ATOM 228 OH TYR A 15 17.364 31.738 14.329 1.00 15.20 O
ATOM 230 CE2 TYR A 15 16.182 33.303 15.621 1.00 17.27 C
ATOM 232 CD2 TYR A 15 15.320 33.610 16.628 1.00 16.64 C
ATOM 234 C TYR A 15 13.925 33.826 20.856 1.00 16.27 C
ATOM 235 O TYR A 15 14.311 35.008 20.744 1.00 17.84 O
ATOM 236 N ASN A 16 13.075 33.432 21.780 1.00 17.21 N
ATOM 238 CA ASN A 16 12.534 34.334 22.811 1.00 17.53 C
ATOM 240 CB ASN A 16 13.628 34.860 23.743 1.00 16.83 C
ATOM 243 CG ASN A 16 13.098 35.265 25.103 1.00 18.27 C
ATOM 244 OD1 ASN A 16 11.901 35.461 25.288 1.00 21.90 O
ATOM 245 ND2 ASN A 16 13.987 35.324 26.075 1.00 17.31 N
ATOM 248 C ASN A 16 11.788 35.480 22.114 1.00 19.04 C
ATOM 249 O ASN A 16 11.940 36.642 22.463 1.00 18.19 O
ATOM 250 N ASP A 17 10.972 35.107 21.135 1.00 18.56 N
ATOM 252 CA ASP A 17 10.176 36.069 20.372 1.00 19.69 C
ATOM 254 CB ASP A 17 11.019 36.634 19.287 1.00 19.45 C
ATOM 257 CG ASP A 17 10.362 37.812 18.579 1.00 20.65 C
ATOM 258 OD1 ASP A 17 9.160 38.017 18.745 1.00 24.61 O
ATOM 259 OD2 ASP A 17 11.034 38.547 17.849 1.00 19.73 O
ATOM 260 C ASP A 17 8.937 35.412 19.778 1.00 19.80 C
ATOM 261 O ASP A 17 9.032 34.693 18.834 1.00 22.05 O
ATOM 262 N GLN A 18 7.791 35.647 20.369 1.00 20.51 N
ATOM 264 CA GLN A 18 6.593 34.957 19.960 1.00 21.49 C
ATOM 266 CB GLN A 18 5.549 35.062 21.054 1.00 22.51 C
ATOM 269 CG GLN A 18 5.917 34.348 22.318 1.00 24.55 C
ATOM 272 CD GLN A 18 6.243 32.907 22.041 1.00 29.84 C
ATOM 273 OE1 GLN A 18 7.347 32.450 22.314 1.00 31.44 O
ATOM 274 NE2 GLN A 18 5.301 32.204 21.457 1.00 28.00 N
ATOM 277 C GLN A 18 6.076 35.511 18.658 1.00 21.92 C
ATOM 278 O GLN A 18 5.213 34.911 18.021 1.00 22.98 O
ATOM 279 N SER A 19 6.697 36.572 18.185 1.00 22.89 N
ATOM 281 CA SER A 19 6.231 37.202 16.951 1.00 23.92 C
ATOM 283 CB SER A 19 6.338 38.715 17.096 1.00 23.69 C
ATOM 286 OG SER A 19 7.627 39.225 16.746 1.00 25.66 O
ATOM 288 C SER A 19 6.947 36.728 15.670 1.00 24.30 C
ATOM 289 O SER A 19 6.454 36.972 14.566 1.00 25.69 O
ATOM 290 N ILE A 20 8.079 36.029 15.764 1.O0 23.62 N
ATOM 292 CA ILE A 2O 8.791 35.673 14.529 1.00 23.92 C
ATOM 294 CB ILE A 20 10.104 34.965 14.836 1.00 24.53 C
ATOM 296 CG1 ILE A 20 9.858 33.755 15.727 1.00 22.48 C
ATOM 299 CD1 ILE A 20 11.041 32.826 15.641 1.00 23.83 C
ATOM 303 CG2 ILE A 20 11.127 35.902 15.477 1.00 27.13 C
ATOM 307 C ILE A 20 8.011 34.784 13.573 1.00 23.40 C
ATOM 308 O ILE A 20 7.241 33.913 13.999 1.00 24.30 O
ATOM 309 N THR A 21 8.295 34.963 12.296 1.00 23.97 N
ATOM 311 CA THR A 21 7.686 34.184 11.215 1.00 24.95 C
ATOM 313 CB THR A 21 6.856 35.107 10.283 1.00 24.97 C
ATOM 315 OG1 THR A 21 7.690 36.186 9.842 1.00 27.61 O
ATOM 317 CG2 THR A 21 5.771 35.794 11.039 1.00 28.02 C
ATOM 321 C THR A 21 8.799 33.570 10.392 1.00 23.92 C
ATOM 322 O THR A 21 8.544 32.865 9.419 1.00 23.90 O
ATOM 323 N LYS A 22 10.044 33.862 10.735 1.00 23.93 N
ATOM 325 CA LYS A 22 11.148 33.239 10.041 1.00 24.18 C
ATOM 327 CB LYS A 22 11.386 33.880 8.675 1.00 25.22 C
ATOM 330 CG LYS A 22 11.830 35.314 8.724 1.00 28.95 C
ATOM 333 CD LYS A 22 12.397 35.808 7.348 1.00 32.55 C
ATOM 336 CE LYS A 22 13.701 35.129 6.988 0.10 31.56 C
ATOM 339 NZ LYS A 22 14.274 35.671 5.722 0.10 31.66 N
ATOM 343 C LYS A 22 12.406 33.333 10.903 1.00 23.63 C
ATOM 344 O LYS A 22 12.471 34.145 11.823 1.00 24.17 O
ATOM 345 N THR A 23 13.395 32.491 10.628 1.00 21.41 N
ATOM 347 CA THR A 23 14.661 32.526 11.342 1.00 20.21 C
ATOM 349 CB THR A 23 14.914 31.202 12.030 1.00 20.28 C
ATOM 351 OG1 THR A 23 14.859 30.158 11.034 1.00 19.28 O
ATOM 353 CG2 THR A 23 13.846 30.915 13.074 1.00 21.44 C
ATOM 357 C THR A 23 15.785 32.791 10.384 1.00 20.28 C
ATOM 358 O THR A 23 15.565 32.740 9.182 1.00 19.80 O
ATOM 359 N THR A 24 16.996 33.027 10.908 1.00 19.65 N
ATOM 361 CA THR A 24 18.201 33.246 10.130 1.00 19.91 C
ATOM 363 CB THR A 24 18.532 34.784 9.840 1.00 21.93 C
ATOM 365 OG1 THR A 24 18.685 35.435 11.102 1.00 25.69 O
ATOM 367 CG2 THR A 24 17.402 35.514 9.229 1.00 25.02 C
ATOM 371 C THR A 24 19.407 32.743 10.928 1.00 19.55 C
ATOM 372 O THR A 24 19.372 32.551 12.149 1.00 19.70 O
ATOM 373 N GLY A 25 20.473 32.497 10.225 1.00 17.41 N
ATOM 375 CA GLY A 25 21.716 32.187 10.893 1.00 17.64 C
ATOM 378 C GLY A 25 22.286 30.799 10.641 1.00 16.16 C
ATOM 379 O GLY A 25 21.583 29.936 10.124 1.00 15.92 O
ATOM 380 N GLY A 26 23.548 30.620 11.068 1.00 15.49 N
ATOM 382 CA GLY A 26 24.296 29.380 10.938 1.00 15.44 C
ATOM 385 C GLY A 26 25.166 29.220 9.692 1.00 15.61 C
ATOM 386 O GLY A 26 25.782 28.199 9.493 1.00 15.36 O
ATOM 387 N SER A 27 25.264 30.249 8.861 1.00 17.72 N
ATOM 389 CA SER A 27 26.108 30.182 7.691 1.00 18.45 C
ATOM 391 CB SER A 27 25.990 31.500 6.837 1.00 20.08 C
ATOM 394 OG SER A 27 26.686 32.496 7.490 1.00 26.34 O
ATOM 396 C SER A 27 27.534 29.838 8.029 1.00 17.45 C
ATOM 397 O SER A 27 28.166 30.341 8.969 1.00 17.59 O
ATOM 398 N GLY A 28 28.071 28.913 7.241 1.00 16.01 N
ATOM 400 CA GLY A 28 29.421 28.494 7.385 1.00 16.46 C
ATOM 403 C GLY A 28 29.615 27.360 8.377 1.00 15.36 C
ATOM 404 O GLY A 28 30.739 26.917 8.527 1.00 16.82 O
ATOM 405 N ILE A 29 28.587 26.931 9.076 1.00 14.25 N
ATOM 407 CA ILE A 29 28.782 25.832 10.044 1.00 13.92 C
ATOM 409 CB ILE A 29 28.057 26.170 11.335 1.00 14.10 C
ATOM 411 CG1 ILE A 29 28.482 27.563 11.856 1.00 13.61 C
ATOM 414 CD1 ILE A 29 29.986 27.710 12.081 1.00 15.86 C
ATOM 418 CG2 ILE A 29 28.269 25.076 12.417 1.00 14.40 C
ATOM 422 C ILE A 29 28.143 24.586 9.459 1.00 14.30 C
ATOM 423 O ILE A 29 27.190 24.708 8.690 1.00 14.55 O
ATOM 424 N LYS A 30 28.614 23.402 9.853 1.00 13.73 N
ATOM 426 CA LYS A 30 28.008 22.173 9.422 1.00 13.73 C
ATOM 428 CB LYS A 30 29.019 21.204 8.860 1.00 14.64 C
ATOM 431 CG LYS A 30 30.072 21.822 7.951 1.00 15.03 C
ATOM 434 CD LYS A 30 29.438 22.566 6.745 1.00 16.42 C
ATOM 437 CE LYS A 30 30.497 23.364 5.987 1.00 19.44 C
ATOM 440 NZ LYS A 30 29.865 24.009 4.752 1.00 17.01 N
ATOM 444 C LYS A 30 27.354 21.482 10.655 1.00 13.57 C
ATOM 445 O LYS A 30 27.978 21.473 11.716 1.00 14.48 O
ATOM 446 N VAL A 31 26.163 20.941 10.498 1.00 13.11 N
ATOM 448 CA VAL A 31 25.572 20.118 11.583 1.00 13.65 C
ATOM 450 CB VAL A 31 24.249 20.639 12.061 1.00 13.16 C
ATOM 452 CG1 VAL A 31 23.726 19.743 13.173 1.00 15.78 C
ATOM 456 CG2 VAL A 31 24.401 22.058 12.573 1.00 12.55 C
ATOM 460 C VAL A 31 25.470 18.708 11.047 1.00 14.30 C
ATOM 461 O VAL A 31 24.828 18.458 10.003 1.00 14.74 O
ATOM 462 N ALA A 32 26.129 17.789 11.737 1.00 14.62 N
ATOM 464 CA ALA A 32 26.092 16.387 11.366 1.00 13.46 C
ATOM 466 CB ALA A 32 27.419 15.728 11.606 1.00 11.29 C
ATOM 470 C ALA A 32 24.972 15.696 12.149 1.00 13.08 C
ATOM 471 O ALA A 32 25.056 15.556 13.393 1.00 12.55 O
ATOM 472 N VAL A 33 23.916 15.340 11.435 1.00 10.76 N
ATOM 474 CA VAL A 33 22.778 14.654 12.038 1.00 11.75 C
ATOM 476 CB VAL A 33 21.468 15.152 11.453 1.00 11.00 C
ATOM 478 CG1 VAL A 33 20.317 14.313 11.935 1.00 13.80 C
ATOM 482 CG2 VAL A 33 21.268 16.618 11.738 1.00 12.19 C
ATOM 486 C VAL A 33 22.959 13.155 11.847 1.00 12.72 C
ATOM 487 O VAL A 33 22.830 12.623 10.715 1.00 11.99 O
ATOM 488 N LEU A 34 23.290 12.466 12.932 1.00 12.34 N
ATOM 490 CA LEU A 34 23.599 11.022 12.949 1.00 11.72 C
ATOM 492 CB LEU A 34 24.811 10.744 13.878 1.00 11.57 C
ATOM 495 CG LEU A 34 26.190 10.819 13.262 1.00 11.59 C
ATOM 497 CD1 LEU A 34 26.515 12.228 12.621 1.00 10.38 C
ATOM 501 CD2 LEU A 34 27.275 10.414 14.265 1.00 12.17 C
ATOM 505 C LEU A 34 22.303 10.366 13.416 1.00 12.33 C
ATOM 506 O LEU A 34 21.964 10.409 14.581 1.00 11.53 O
ATOM 507 N ASP A 35 21.571 9.765 12.490 1.00 11.34 N
ATOM 509 CA ASP A 35 20.224 9.416 12.794 1.00 11.07 C
ATOM 511 CB ASP A 35 19.397 10.677 12.779 1.00 12.91 C
ATOM 514 CG ASP A 35 18.231 10.611 13.697 1.00 11.93 C
ATOM 515 OD1 ASP A 35 17.334 9.791 13.472 1.00 12.81 O
ATOM 516 OD2 ASP A 35 18.166 11.390 14.700 1.00 15.59 O
ATOM 517 C ASP A 35 19.687 8.393 11.816 1.00 12.34 C
ATOM 518 O ASP A 35 20.470 7.623 11.250 1.00 12.33 O
ATOM 519 N THR A 36 18.376 8.385 11.604 1.00 12.33 N
ATOM 521 CA THR A 36 17.783 7.395 10.702 1.00 13.86 C
ATOM 523 CB THR A 36 16.312 7.198 10.972 1.00 13.36 C
ATOM 525 OG1 THR A 36 15.603 8.446 10.753 1.00 14.42 O
ATOM 527 CG2 THR A 36 16.058 6.781 12.383 1.00 11.98 C
ATOM 531 C THR A 36 17.933 7.710 9.199 1.00 14.93 C
ATOM 532 O THR A 36 17.341 7.023 8.379 1.00 15.02 O
ATOM 533 N GLY A 37 18.699 8.735 8.885 1.00 15.27 N
ATOM 535 CA GLY A 37 18.838 9.282 7.530 1.00 15.54 C
ATOM 538 C GLY A 37 18.041 10.594 7.487 1.00 16.06 C
ATOM 539 O GLY A 37 17.413 10.973 8.482 1.00 14.08 O
ATOM 540 N VAL A 38 18.065 11.292 6.337 1.00 16.27 N
ATOM 542 CA VAL A 38 17.315 12.547 6.177 1.00 15.20 C
ATOM 544 CB VAL A 38 18.214 13.784 6.447 1.00 15.83 C
ATOM 546 CG1 VAL A 38 17.501 15.075 6.182 1.00 16.87 C
ATOM 550 CG2 VAL A 38 18.774 13.766 7.839 1.00 17.47 C
ATOM 554 C VAL A 38 16.863 12.628 4.695 1.00 16.04 C
ATOM 555 O VAL A 38 17.622 12.277 3.793 1.00 14.66 O
ATOM 556 N TYR A 39 15.623 13.008 4.532 1.00 18.21 N
ATOM 558 CA TYR A 39 15.046 13.247 3.214 1.00 19.90 C
ATOM 560 CB TYR A 39 13.564 13.150 3.366 1.00 18.60 C
ATOM 563 CG TYR A 39 12.795 13.480 2.082 1.00 23.59 C
ATOM 564 CD1 TYR A 39 13.278 13.110 0.833 1.00 27.19 C
ATOM 566 CE1 TYR A 39 12.555 13.413 -0.309 1.00 30.38 C
ATOM 568 CZ TYR A 39 11.391 14.129 -0.226 1.00 31.18 C
ATOM 569 OH TYR A 39 10.734 14.412 -1.434 1.00 30.34 O
ATOM 571 CE2 TYR A 39 10.912 14.528 1.005 1.00 29.74 C
ATOM 573 CD2 TYR A 39 11.623 14.208 2.144 1.00 23.70 C
ATOM 575 C TYR A 39 15.495 14.623 2.786 1.00 19.47 C
ATOM 576 O TYR A 39 14.795 15.631 2.992 1.00 22.39 O
ATOM 577 N THR A 40 16.675 14.659 2.240 1.00 22.23 N
ATOM 579 CA THR A 40 17.366 15.869 1.904 1.00 23.84 C
ATOM 581 CB THR A 40 18.797 15.520 1.499 1.00 25.17 C
ATOM 583 OG1 THR A 40 18.841 14.473 0.518 1.00 27.20 O
ATOM 585 CG2 THR A 40 19.633 14.890 2.687 1.00 23.66 C
ATOM 589 C THR A 40 16.650 16.659 0.804 1.00 25.31 C
ATOM 590 O THR A 40 17.008 17.803 0.566 1.00 25.93 O
ATOM 591 N SER A 41 15.671 16.051 0.147 1.00 25.63 N
ATOM 593 CA SER A 41 14.953 16.703 -0.942 1.00 26.05 C
ATOM 595 CB SER A 41 14.662 15.676 -2.047 1.00 25.60 C
ATOM 598 OG SER A 41 15.836 15.411 -2.759 1.00 26.14 O
ATOM 600 C SER A 41 13.669 17.317 -0.445 1.00 26.09 C
ATOM 601 O SER A 41 12.896 17.889 -1.232 1.00 26.66 O
ATOM 602 N HIS A 42 13.366 17.179 0.857 1.00 22.90 N
ATOM 604 CA HIS A 42 12.245 17.917 1.419 1.00 21.28 C
ATOM 606 CB HIS A 42 12.224 17.792 2.927 1.00 21.28 C
ATOM 609 CG HIS A 42 10.988 18.267 3.562 1.00 18.79 C
ATOM 610 ND1 HIS A 42 10.616 19.591 3.556 1.00 17.72 N
ATOM 612 CE1 HIS A 42 9.482 19.706 4.197 1.00 14.42 C
ATOM 614 NE2 HIS A 42 9.124 18.516 4.654 1.00 18.07 N
ATOM 616 CD2 HIS A 42 10.028 17.601 4.230 1.00 15.85 C
ATOM 618 C HIS A 42 12.427 19.379 1.036 1.00 20.43 C
ATOM 619 O HIS A 42 13.543 19.890 1.077 1.00 19.85 O
ATOM 620 N LEU A 43 11.326 20.044 0.686 1.00 21.20 N
ATOM 622 CA LEU A 43 11.380 21.409 0.210 1.00 21.25 C
ATOM 624 CB LEU A 43 10.030 21.945 -0.087 1.00 22.55 C
ATOM 627 CG LEU A 43 9.448 21.512 -1.433 1.00 25.81 C
ATOM 629 CD1 LEU A 43 8.021 21.976 -1.464 1.00 27.58 C
ATOM 633 CD2 LEU A 43 10.234 22.108 -2.559 1.00 27.86 C
ATOM 637 C LEU A 43 12.023 22.311 1.227 1.00 21.05 C
ATOM 638 O LEU A 43 12.699 23.255 0.879 1.00 18.87 O
ATOM 639 N ASP A 44 11.847 22.042 2.500 1.00 21.71 N
ATOM 641 CA ASP A 44 12.514 22.885 3.487 1.00 20.87 C
ATOM 643 CB ASP A 44 11.642 22.917 4.719 1.00 21.17 C
ATOM 646 CG ASP A 44 10.262 23.417 4.441 1.00 23.00 C
ATOM 647 OD1 ASP A 44 10.060 24.154 3.406 1.00 21.93 O
ATOM 648 OD2 ASP A 44 9.325 23.156 5.206 1.00 16.28 O
ATOM 649 C ASP A 44 13.962 22.528 3.812 1.00 21.02 C
ATOM 650 O ASP A 44 14.593 23.214 4.604 1.00 18.05 O
ATOM 651 N LEU A 45 14.488 21.431 3.252 1.00 18.30 N
ATOM 653 CA LEU A 45 15.868 21.070 3.445 1.00 19.90 C
ATOM 655 CB LEU A 45 15.922 19.624 4.024 1.00 18.80 C
ATOM 658 CG LEU A 45 15.174 19.394 5.300 1.00 18.65 C
ATOM 660 CD1 LEU A 45 15.424 17.925 5.756 1.00 18.05 C
ATOM 664 CD2 LEU A 45 15.714 20.351 6.357 1.00 20.33 C
ATOM 668 C LEU A 45 16.750 21.110 2.197 1.00 20.37 C
ATOM 669 O LEU A 45 17.960 20.890 2.251 1.00 22.13 O
ATOM 670 N ALA A 46 16.104 21.400 1.079 1.00 22.51 N
ATOM 672 CA ALA A 46 16.728 21.327 -0.210 1.00 21.13 C
ATOM 674 CB ALA A 46 15.738 21.695 -1.365 1.00 21.15 C
ATOM 678 C ALA A 46 17.880 22.199 -0.244 1.00 20.28 C
ATOM 679 O ALA A 46 17.806 23.344 0.177 1.00 22.66 O
ATOM 680 N GLY A 47 18.959 21.639 -0.759 1.00 20.67 N
ATOM 682 CA GLY A 47 20.217 22.320 -0.968 1.00 21.84 C
ATOM 685 C GLY A 47 21.042 22.419 0.291 1.00 21.53 C
ATOM 686 O GLY A 47 22.226 22.881 0.280 1.00 24.34 O
ATOM 687 N SER A 48 20.522 21.910 1.392 1.00 22.52 N
ATOM 689 CA SER A 48 21.310 21.980 2.610 1.00 21.98 C
ATOM 691 CB ASER A 48 20.384 22.083 3.833 0.50 22.54 C
ATOM 692 CB BSER A 48 20.408 22.073 3.814 0.50 22.26 C
ATOM 697 OG ASER A 48 19.449 21.001 3.944 0.50 23.88 O
ATOM 698 OG BSER A 48 19.660 23.258 3.738 0.50 21.10 O
ATOM 701 C SER A 48 22.295 20.852 2.826 1.00 21.47 C
ATOM 702 O SER A 48 23.317 21.066 3.466 1.00 21.64 O
ATOM 703 N ALA A 49 22.035 19.670 2.285 1.00 20.96 N
ATOM 705 CA ALA A 49 22.951 18.532 2.483 1.00 22.38 C
ATOM 707 CB ALA A 49 22.192 17.247 2.068 1.00 22.64 C
ATOM 711 C ALA A 49 24.233 18.644 1.718 1.00 23.21 C
ATOM 712 O ALA A 49 24.228 18.551 0.500 1.00 26.19 O
ATOM 713 N GLU A 50 25.328 18.866 2.426 1.00 20.40 N
ATOM 715 CA GLU A 50 26.598 18.826 1.753 1.00 21.76 C
ATOM 717 CB GLU A 50 27.625 19.892 2.250 1.00 22.32 C
ATOM 720 CG GLU A 50 27.374 21.244 1.591 1.00 26.62 C
ATOM 723 CD GLU A 50 28.046 22.421 2.279 1.00 30.59 C
ATOM 724 OE1 GLU A 50 28.886 22.227 3.181 1.00 24.43 O
ATOM 725 OE2 GLU A 50 27.683 23.561 1.918 1.00 35.88 O
ATOM 726 C GLU A 50 27.208 17.435 1.866 1.00 20.83 C
ATOM 727 O GLU A 50 28.257 17.188 1.220 1.00 21.81 O
ATOM 728 N GLN A 51 26.761 16.586 2.783 1.00 19.08 N
ATOM 730 CA GLN A 51 27.273 15.186 2.847 1.00 18.38 C
ATOM 732 CB GLN A 51 28.416 14.936 3.863 1.00 18.98 C
ATOM 735 CG GLN A 51 29.720 15.707 3.698 1.00 16.56 C
ATOM 738 CD GLN A 51 30.864 15.082 4.418 1.00 18.35 C
ATOM 739 OE1 GLN A 51 30.728 14.001 4.993 1.00 16.59 O
ATOM 740 NE2 GLN A 51 32.021 15.746 4.421 1.00 18.88 N
ATOM 743 C GLN A 51 26.048 14.303 3.122 1.00 18.15 C
ATOM 744 O GLN A 51 25.088 14.739 3.753 1.00 17.95 O
ATOM 745 N CYS A 52 26.032 13.097 2.549 1.00 19.15 N
ATOM 747 CA CYS A 52 24.933 12.197 2.657 1.00 19.58 C
ATOM 749 CB CYS A 52 23.994 12.383 1.463 1.00 20.58 C
ATOM 752 SG CYS A 52 22.757 11.113 1.313 1.00 23.23 S
ATOM 753 C CYS A 52 25.609 10.827 2.666 1.00 19.62 C
ATOM 754 O CYS A 52 26.112 10.376 1.630 1.00 17.75 O
ATOM 755 N LYS A 53 25.706 10.188 3.841 1.00 18.28 N
ATOM 757 CA LYS A 53 26.435 8.938 3.934 1.00 17.30 C
ATOM 759 CB LYS A 53 27.835 9.165 4.542 1.00 17.03 C
ATOM 762 CG LYS A 53 28.733 10.042 3.720 1.00 16.05 C
ATOM 765 CD LYS A 53 30.097 10.281 4.325 1.00 17.76 C
ATOM 768 CE LYS A 53 31.031 11.033 3.333 1.00 17.09 C
ATOM 771 NZ LYS A 53 32.138 11.733 3.893 1.00 19.33 N
ATOM 775 C LYS A 53 25.698 7.913 4.801 1.00 18.20 C
ATOM 776 O LYS A 53 24.966 8.299 5.712 1.00 15.09 O
ATOM 777 N ASP A 54 25.905 6.619 4.518 1.00 15.90 N
ATOM 779 CA ASP A 54 25.186 5.563 5.218 1.00 17.38 C
ATOM 781 CB ASP A 54 24.244 4.911 4.223 1.00 17.91 C
ATOM 784 CG ASP A 54 23.222 3.960 4.825 1.00 20.51 C
ATOM 785 OD1 ASP A 54 23.261 3.554 6.029 1.00 15.70 O
ATOM 786 OD2 ASP A 54 22.292 3.563 4.088 1.00 19.49 O
ATOM 787 C ASP A 54 26.131 4.552 5.807 1.00 17.88 C
ATOM 788 O ASP A 54 26.969 3.968 5.093 1.00 17.08 O
ATOM 789 N PHE A 55 25.998 4.356 7.135 1.00 15.74 N
ATOM 791 CA PHE A 55 26.865 3.464 7.867 1.00 15.03 C
ATOM 793 CB PHE A 55 27.359 4.168 9.131 1.00 13.99 C
ATOM 796 CG PHE A 55 28.268 5.336 8.844 1.00 15.45 C
ATOM 797 CD1 PHE A 55 27.753 6.544 8.432 1.00 15.76 C
ATOM 799 CE1 PHE A 55 28.616 7.657 8.155 1.00 14.10 C
ATOM 801 CZ PHE A 55 29.907 7.536 8.256 1.00 13.98 C
ATOM 803 CE2 PHE A 55 30.431 6.303 8.656 1.00 15.61 C
ATOM 805 CD2 PHE A 55 29.594 5.232 8.950 1.00 14.62 C
ATOM 807 C PHE A 55 26.160 2.191 8.265 1.00 15.07 C
ATOM 808 O PHE A 55 26.732 1.387 9.025 1.00 15.44 O
ATOM 809 N THR A 56 24.962 1.994 7.769 1.00 15.31 N
ATOM 811 CA THR A 56 24.149 0.858 8.159 1.00 16.77 C
ATOM 813 CB THR A 56 22.724 1.253 8.463 1.00 17.17 C
ATOM 815 OG1 THR A 56 22.006 1.623 7.272 1.00 15.48 O
ATOM 817 CG2 THR A 56 22.628 2.535 9.443 1.00 13.67 C
ATOM 821 C THR A 56 24.134 -0.328 7.166 1.00 20.28 C
ATOM 822 O THR A 56 23.451 -1.319 7.407 1.00 21.69 O
ATOM 823 N GLN A 57 24.852 -0.239 6.069 1.00 22.81 N
ATOM 825 CA GLN A 57 24.736 -1.314 5.061 1.00 25.52 C
ATOM 827 CB GLN A 57 24.681 -0.724 3.646 1.00 25.67 C
ATOM 830 CG GLN A 57 23.521 0.217 3.502 1.00 27.65 C
ATOM 833 CD GLN A 57 23.366 0.800 2.117 1.00 36.31 C
ATOM 834 OE1 GLN A 57 23.871 0.240 1.156 1.00 35.97 O
ATOM 835 NE2 GLN A 57 22.686 1.938 2.016 1.00 30.80 N
ATOM 838 C GLN A 57 25.848 -2.331 5.196 1.00 28.75 C
ATOM 839 O GLN A 57 26.735 -2.182 6.034 1.00 28.60 O
ATOM 840 N SER A 58 25.792 -3.388 4.363 1.00 32.27 N
ATOM 842 CA SER A 58 26.798 -4.440 4.371 1.00 34.96 C
ATOM 844 CB SER A 58 26.488 -5.494 3.291 1.00 35.23 C
ATOM 847 OG SER A 58 25.088 -5.548 3.041 1.00 37.60 O
ATOM 849 C SER A 58 28.149 -3.762 4.140 1.00 35.56 C
ATOM 850 O SER A 58 29.096 -3.989 4.843 1.00 36.58 O
ATOM 851 N ASN A 59 28.224 -2.889 3.147 1.00 37.91 N
ATOM 853 CA ASN A 59 29.409 -2.054 3.003 1.00 38.41 C
ATOM 855 CB ASN A 59 29.288 -1.232 1.739 1.00 39.92 C
ATOM 858 CG ASN A 59 30.172 -1.727 0.636 1.00 44.62 C
ATOM 859 OD1 ASN A 59 31.413 -1.752 0.759 1.00 52.42 O
ATOM 860 ND2 ASN A 59 29.547 -2.121 -0.468 1.00 50.97 N
ATOM 863 C ASN A 59 29.421 -1.061 4.156 1.00 37.64 C
ATOM 864 O ASN A 59 28.436 -0.360 4.338 1.00 37.26 O
ATOM 865 N PRO A 60 30.474 -1.028 4.961 1.00 37.50 N
ATOM 866 CA PRO A 60 30.591 -0.066 6.064 1.00 36.81 C
ATOM 868 CB PRO A 60 32.016 -0.315 6.585 1.00 37.80 C
ATOM 871 CG PRO A 60 32.661 -1.116 5.519 1.00 38.85 C
ATOM 874 CD PRO A 60 31.589 -1.986 4.997 1.00 38.04 C
ATOM 877 C PRO A 60 30.421 1.431 5.770 1.00 35.74 C
ATOM 878 O PRO A 60 30.266 2.188 6.749 1.00 34.22 O
ATOM 879 N LEU A 61 30.478 1.876 4.517 1.00 33.77 N
ATOM 881 CA LEU A 61 30.183 3.278 4.258 1.00 33.86 C
ATOM 883 CB LEU A 61 31.403 4.170 4.541 1.00 34.63 C
ATOM 886 CG LEU A 61 31.122 5.691 4.652 1.00 38.34 C
ATOM 888 CD1 LEU A 61 32.418 6.454 4.765 1.00 41.14 C
ATOM 892 CD2 LEU A 61 30.383 6.236 3.501 1.00 40.32 C
ATOM 896 C LEU A 61 29.681 3.440 2.838 1.00 31.90 C
ATOM 897 O LEU A 61 30.371 3.109 1.887 1.00 32.30 O
ATOM 898 N VAL A 62 28.452 3.862 2.682 1.00 29.42 N
ATOM 900 CA VAL A 62 27.944 4.129 1.363 1.00 29.40 C
ATOM 902 CB VAL A 62 26.721 3.365 1.091 1.00 28.97 C
ATOM 904 CG1 VAL A 62 26.082 3.877 -0.187 1.00 30.81 C
ATOM 908 CG2 VAL A 62 27.060 1.874 1.015 1.00 31.48 C
ATOM 912 C VAL A 62 27.768 5.625 1.255 1.00 27.76 C
ATOM 913 O VAL A 62 27.015 6.233 1.970 1.00 26.96 O
ATOM 914 N ASP A 63 28.646 6.224 0.470 1.00 28.18 N
ATOM 916 CA ASP A 63 28.600 7.643 0.235 1.00 26.20 C
ATOM 918 CB ASP A 63 29.993 8.062 -0.215 1.00 26.90 C
ATOM 921 CG ASP A 63 30.222 9.517 -0.099 1.00 25.49 C
ATOM 922 OD1 ASP A 63 29.290 10.281 -0.017 1.00 26.02 O
ATOM 923 OD2 ASP A 63 31.318 10.031 -0.150 1.00 28.08 O
ATOM 924 C ASP A 63 27.571 7.929 -0.826 1.00 27.79 C
ATOM 925 O ASP A 63 27.455 7.199 -1.812 1.00 27.28 O
ATOM 926 N GLY A 64 26.753 8.936 -0.581 1.00 26.48 N
ATOM 928 CA GLY A 64 25.703 9.316 -1.502 1.00 25.76 C
ATOM 931 C GLY A 64 24.357 8.742 -1.234 1.00 25.62 C
ATOM 932 O GLY A 64 23.474 8.881 -2.053 1.00 28.14 O
ATOM 933 N SER A 65 24.184 8.096 -0.080 1.00 22.83 N
ATOM 935 CA SER A 65 22.953 7.499 0.304 1.00 22.85 C
ATOM 937 CB SER A 65 23.003 6.005 0.117 1.00 23.23 C
ATOM 940 OG SER A 65 21.699 5.584 0.027 1.00 29.80 O
ATOM 942 C SER A 65 22.705 7.773 1.749 1.00 21.08 C
ATOM 943 O SER A 65 23.671 7.638 2.504 1.00 19.41 O
ATOM 944 N CYS A 66 21.521 8.181 2.140 1.00 20.00 N
ATOM 946 CA CYS A 66 21.278 8.539 3.546 1.00 20.11 C
ATOM 948 CB CYS A 66 22.034 9.822 3.885 1.00 19.63 C
ATOM 951 SG CYS A 66 21.484 11.254 2.900 1.00 19.95 S
ATOM 952 C CYS A 66 19.803 8.601 3.712 1.00 18.81 C
ATOM 953 O CYS A 66 19.168 9.468 4.308 1.00 17.95 O
ATOM 954 N THR A 67 19.180 7.568 3.214 1.00 19.39 N
ATOM 956 CA THR A 67 17.768 7.596 3.075 1.00 19.72 C
ATOM 958 CB THR A 67 17.481 6.628 1.924 1.00 20.77 C
ATOM 960 OG1 THR A 67 18.082 7.189 0.735 1.00 26.00 O
ATOM 962 CG2 THR A 67 16.113 6.443 1.665 1.00 23.79 C
ATOM 966 C THR A 67 16.941 7.325 4.315 1.00 18.14 C
ATOM 967 O THR A 67 17.066 6.297 4.990 1.00 16.62 O
ATOM 968 N ASP A 68 16.070 8.278 4.623 1.00 17.54 N
ATOM 970 CA ASP A 68 15.191 8.149 5.786 1.00 17.68 C
ATOM 972 CB ASP A 68 14.877 9.530 6.360 1.00 16.82 C
ATOM 975 CG ASP A 68 14.131 9.480 7.697 1.00 17.49 C
ATOM 976 OD1 ASP A 68 13.988 8.380 8.314 1.00 14.56 O
ATOM 977 OD2 ASP A 68 13.610 10.516 8.221 1.00 16.31 O
ATOM 978 C ASP A 68 13.909 7.425 5.423 1.00 19.14 C
ATOM 979 O ASP A 68 13.100 7.936 4.626 1.00 19.83 O
ATOM 980 N ARG A 69 13.688 6.262 6.023 1.00 19.38 N
ATOM 982 CA ARG A 69 12.427 5.549 5.858 1.00 20.20 C
ATOM 984 CB ARG A 69 12.665 4.106 5.357 1.00 20.57 C
ATOM 987 CG ARG A 69 13.461 4.061 4.081 1.00 23.84 C
ATOM 990 CD ARG A 69 13.499 2.688 3.401 1.00 28.11 C
ATOM 993 NE ARG A 69 14.384 2.688 2.239 1.00 31.97 N
ATOM 995 CZ ARG A 69 15.683 2.433 2.284 1.00 34.34 C
ATOM 996 NH1 ARG A 69 16.288 2.155 3.437 1.00 33.57 N
ATOM 999 NH2 ARG A 69 16.416 2.464 1.173 1.00 37.78 N
ATOM 1002 C ARG A 69 11.615 5.543 7.120 1.00 20.20 C
ATOM 1003 O ARG A 69 10.605 4.861 7.222 1.00 19.58 O
ATOM 1004 N GLN A 70 12.022 6.341 8.120 1.00 18.56 N
ATOM 1006 CA GLN A 70 11.359 6.330 9.404 1.00 18.67 C
ATOM 1008 CB GLN A 70 12.459 6.087 10.480 1.00 17.38 C
ATOM 1011 CG GLN A 70 11.887 5.512 11.734 1.00 24.45 C
ATOM 1014 CD GLN A 70 11.094 6.496 12.618 1.00 29.69 C
ATOM 1015 OE1 GLN A 70 11.259 7.719 12.568 1.00 28.81 O
ATOM 1016 NE2 GLN A 70 10.180 5.934 13.390 1.00 36.98 N
ATOM 1019 C GLN A 70 10.678 7.677 9.729 1.00 16.99 C
ATOM 1020 O GLN A 70 9.502 7.745 10.177 1.00 18.53 O
ATOM 1021 N GLY A 71 11.448 8.740 9.546 1.00 17.00 N
ATOM 1023 CA GLY A 71 10.936 10.086 9.792 1.00 16.91 C
ATOM 1026 C GLY A 71 11.766 10.862 10.826 1.00 16.73 C
ATOM 1027 O GLY A 71 12.023 12.040 10.683 1.00 16.08 O
ATOM 1028 N HIS A 72 12.190 10.148 11.848 1.00 15.53 N
ATOM 1030 CA HIS A 72 12.902 10.764 12.965 1.00 14.82 C
ATOM 1032 CB HIS A 72 13.305 9.625 13.926 1.00 14.91 C
ATOM 1035 CG HIS A 72 13.996 10.088 15.170 1.00 11.42 C
ATOM 1036 ND1 HIS A 72 15.356 10.264 15.228 1.00 11.65 N
ATOM 1038 CE1 HIS A 72 15.690 10.620 16.456 1.00 15.57 C
ATOM 1040 NE2 HIS A 72 14.603 10.660 17.194 1.00 12.24 N
ATOM 1042 CD2 HIS A 72 13.527 10.309 16.414 1.00 15.18 C
ATOM 1044 C HIS A 72 14.077 11.632 12.515 1.00 14.31 C
ATOM 1045 O HIS A 72 14.157 12.811 12.906 1.00 14.46 O
ATOM 1046 N GLY A 73 14.993 11.101 11.686 1.00 13.23 N
ATOM 1048 CA GLY A 73 16.140 11.851 11.227 1.00 13.67 C
ATOM 1051 C GLY A 73 15.743 13.097 10.452 1.00 14.47 C
ATOM 1052 O GLY A 73 16.388 14.147 10.556 1.00 14.58 O
ATOM 1053 N THR A 74 14.691 12.976 9.638 1.00 14.43 N
ATOM 1055 CA THR A 74 14.223 14.163 8.902 1.00 14.75 C
ATOM 1057 CB THR A 74 13.166 13.722 7.889 1.00 15.14 C
ATOM 1059 OG1 THR A 74 13.832 12.851 6.979 1.00 14.14 O
ATOM 1061 CG2 THR A 74 12.703 14.949 7.052 1.00 17.07 C
ATOM 1065 C THR A 74 13.672 15.256 9.779 1.00 13.89 C
ATOM 1066 O THR A 74 13.964 16.449 9.549 1.00 14.36 O
ATOM 1067 N HIS A 75 12.985 14.834 10.823 1.00 13.97 N
ATOM 1069 CA HIS A 75 12.345 15.653 11.803 1.00 13.53 C
ATOM 1071 CB HIS A 75 11.464 14.793 12.693 1.00 14.00 C
ATOM 1074 CG HIS A 75 10.525 15.543 13.566 1.00 13.88 C
ATOM 1075 ND1 HIS A 75 10.923 16.209 14.706 1.00 13.19 N
ATOM 1077 CE1 HIS A 75 9.888 16.830 15.235 1.00 15.22 C
ATOM 1079 NE2 HIS A 75 8.826 16.616 14.465 1.00 15.33 N
ATOM 1081 CD2 HIS A 75 9.203 15.822 13.415 1.00 14.61 C
ATOM 1083 C HIS A 75 13.464 16.423 12.565 1.00 14.20 C
ATOM 1084 O HIS A 75 13.447 17.650 12.685 1.00 11.71 O
ATOM 1085 N VAL A 76 14.436 15.685 13.031 1.00 13.61 N
ATOM 1087 CA VAL A 76 15.543 16.273 13.761 1.00 13.90 C
ATOM 1089 CB VAL A 76 16.471 15.117 14.276 1.00 12.59 C
ATOM 1091 CG1 VAL A 76 17.771 15.657 14.716 1.00 13.85 C
ATOM 1095 CG2 VAL A 76 15.788 14.354 15.381 1.00 13.36 C
ATOM 1099 C VAL A 76 16.280 17.319 12.925 1.00 13.76 C
ATOM 1100 O VAL A 76 16.549 18.419 13.362 1.00 13.81 O
ATOM 1101 N ALA A 77 16.598 16.976 11.693 1.00 13.31 N
ATOM 1103 CA ALA A 77 17.316 17.850 10.844 1.00 13.43 C
ATOM 1105 CB ALA A 77 17.586 17.164 9.553 1.00 12.82 C
ATOM 1109 C ALA A 77 16.538 19.154 10.631 1.00 13.42 C
ATOM 1110 O ALA A 77 17.137 20.256 10.595 1.00 16.51 O
ATOM 1111 N GLY A 78 15.223 19.047 10.501 1.00 13.22 N
ATOM 1113 CA GLY A 78 14.413 20.237 10.270 1.00 14.59 C
ATOM 1116 C GLY A 78 14.431 21.221 11.448 1.00 14.40 C
ATOM 1117 O GLY A 78 14.427 22.440 11.294 1.00 14.85 O
ATOM 1118 N THR A 79 14.537 20.673 12.643 1.00 12.64 N
ATOM 1120 CA THR A 79 14.546 21.535 13.817 1.00 11.83 C
ATOM 1122 CB THR A 79 14.350 20.656 15.063 1.00 11.71 C
ATOM 1124 OG1 THR A 79 12.990 20.162 15.166 1.00 12.60 O
ATOM 1126 CG2 THR A 79 14.569 21.491 16.347 1.00 11.10 C
ATOM 1130 C THR A 79 15.842 22.248 13.795 1.00 12.20 C
ATOM 1131 O THR A 79 15.917 23.440 14.122 1.00 12.14 O
ATOM 1132 N VAL A 80 16.917 21.568 13.358 1.00 11.44 N
ATOM 1134 CA VAL A 80 18.195 22.225 13.293 1.00 11.80 C
ATOM 1136 CB VAL A 80 19.299 21.273 12.865 1.00 11.91 C
ATOM 1138 CG1 VAL A 80 20.637 21.963 12.687 1.00 13.34 C
ATOM 1142 CG2 VAL A 80 19.520 20.158 13.884 1.00 12.77 C
ATOM 1146 C VAL A 80 18.216 23.369 12.266 1.00 13.39 C
ATOM 1147 O VAL A 80 18.646 24.514 12.553 1.00 12.65 O
ATOM 1148 N LEU A 81 17.751 23.054 11.069 1.00 13.69 N
ATOM 1150 CA LEU A 81 18.057 23.946 9.965 1.00 14.13 C
ATOM 1152 CB LEU A 81 19.454 23.675 9.439 1.00 14.13 C
ATOM 1155 CG LEU A 81 19.893 22.189 9.225 1.00 11.54 C
ATOM 1157 CD1 LEU A 81 19.058 21.552 8.105 1.00 15.65 C
ATOM 1161 CD2 LEU A 81 21.308 22.059 8.854 1.00 14.83 C
ATOM 1165 C LEU A 81 17.043 24.065 8.827 1.00 15.14 C
ATOM 1166 O LEU A 81 17.442 24.518 7.766 1.00 17.76 O
ATOM 1167 N ALA A 82 15.791 23.694 9.035 1.00 15.38 N
ATOM 1169 CA ALA A 82 14.830 23.894 7.920 1.00 16.54 C
ATOM 1171 CB ALA A 82 13.485 23.412 8.253 1.00 16.56 C
ATOM 1175 C ALA A 82 14.807 25.381 7.616 1.00 17.73 C
ATOM 1176 O ALA A 82 14.873 26.246 8.522 1.00 16.11 O
ATOM 1177 N HIS A 83 14.637 25.678 6.321 1.00 18.61 N
ATOM 1179 CA HIS A 83 14.802 27.048 5.845 1.00 17.82 C
ATOM 1181 CB HIS A 83 16.057 27.116 4.996 1.00 18.66 C
ATOM 1184 CG HIS A 83 16.040 26.187 3.831 1.00 19.55 C
ATOM 1185 ND1 HIS A 83 14.935 26.066 3.023 1.00 23.39 N
ATOM 1187 CE1 HIS A 83 15.196 25.205 2.056 1.00 24.12 C
ATOM 1189 NE2 HIS A 83 16.395 24.706 2.259 1.00 24.21 N
ATOM 1191 CD2 HIS A 83 16.960 25.326 3.349 1.00 22.73 C
ATOM 1193 C HIS A 83 13.606 27.689 5.119 1.00 19.24 C
ATOM 1194 O HIS A 83 13.802 28.694 4.468 1.00 20.21 O
ATOM 1195 N GLY A 84 12.433 27.158 5.342 1.00 19.88 N
ATOM 1197 CA GLY A 84 11.151 27.653 4.874 1.00 23.01 C
ATOM 1200 C GLY A 84 10.891 27.373 3.388 1.00 23.83 C
ATOM 1201 O GLY A 84 9.816 27.693 2.873 1.00 25.88 O
ATOM 1202 N GLY A 85 11.891 26.852 2.716 1.00 25.14 N
ATOM 1204 CA GLY A 85 11.754 26.452 1.333 1.00 28.31 C
ATOM 1207 C GLY A 85 11.845 27.607 0.361 1.00 30.82 C
ATOM 1208 O GLY A 85 11.704 28.777 0.750 1.00 32.32 O
ATOM 1209 N SER A 86 12.066 27.253 -0.910 1.00 33.23 N
ATOM 1211 CA SER A 86 12.332 28.220 -1.982 1.00 35.37 C
ATOM 1213 CB SER A 86 12.287 27.551 -3.374 1.00 35.51 C
ATOM 1216 OG SER A 86 11.022 26.920 -3.531 1.00 36.16 O
ATOM 1218 C SER A 86 11.323 29.323 -1.984 1.00 35.85 C
ATOM 1219 O SER A 86 11.673 30.481 -2.155 1.00 37.71 O
ATOM 1220 N ASN A 87 10.066 28.993 -1.784 1.00 36.18 N
ATOM 1222 CA ASN A 87 9.060 30.024 -1.844 1.00 37.05 C
ATOM 1224 CB ASN A 87 7.842 29.472 -2.589 1.00 37.33 C
ATOM 1227 CG ASN A 87 6.943 28.626 -1.702 1.00 40.53 C
ATOM 1228 OD1 ASN A 87 7.323 28.240 -0.581 1.00 40.83 O
ATOM 1229 ND2 ASN A 87 5.732 28.329 -2.205 1.00 39.22 N
ATOM 1232 C ASN A 87 8.678 30.600 -0.469 1.00 35.97 C
ATOM 1233 O ASN A 87 7.564 31.143 -0.295 1.00 36.81 O
ATOM 1234 N GLY A 88 9.554 30.402 0.526 1.00 34.13 N
ATOM 1236 CA GLY A 88 9.307 30.979 1.841 1.00 32.36 C
ATOM 1239 C GLY A 88 8.149 30.556 2.701 1.00 30.27 C
ATOM 1240 O GLY A 88 7.882 31.189 3.728 1.00 30.72 O
ATOM 1241 N GLN A 89 7.375 29.545 2.305 1.00 28.00 N
ATOM 1243 CA GLN A 89 6.212 29.190 3.117 1.00 27.11 C
ATOM 1245 CB GLN A 89 4.898 29.091 2.269 1.00 28.51 C
ATOM 1248 CG GLN A 89 3.596 28.969 3.114 0.10 26.48 C
ATOM 1251 CD GLN A 89 2.269 28.881 2.318 0.10 25.84 C
ATOM 1252 OE1 GLN A 89 2.243 28.873 1.085 0.10 20.77 O
ATOM 1253 NE2 GLN A 89 1.164 28.811 3.052 0.10 23.86 N
ATOM 1256 C GLN A 89 6.384 27.908 3.974 1.00 26.64 C
ATOM 1257 O GLN A 89 5.463 27.490 4.638 1.00 25.73 O
ATOM 1258 N GLY A 90 7.572 27.312 3.967 1.00 26.19 N
ATOM 1260 CA GLY A 90 7.781 26.104 4.760 1.00 24.89 C
ATOM 1263 C GLY A 90 8.133 26.372 6.223 1.00 25.02 C
ATOM 1264 O GLY A 90 7.940 27.492 6.751 1.00 25.06 O
ATOM 1265 N VAL A 91 8.598 25.330 6.888 1.00 22.83 N
ATOM 1267 CA VAL A 91 8.942 25.462 8.304 1.00 20.77 C
ATOM 1269 CB VAL A 91 8.681 24.116 9.045 1.00 19.91 C
ATOM 1271 CG1 VAL A 91 9.781 23.160 8.797 1.00 21.25 C
ATOM 1275 CG2 VAL A 91 8.463 24.309 10.528 1.00 21.36 C
ATOM 1279 C VAL A 91 10.344 25.938 8.411 1.00 18.60 C
ATOM 1280 O VAL A 91 11.184 25.738 7.532 1.00 19.96 O
ATOM 1281 N TYR A 92 10.632 26.589 9.547 1.00 18.11 N
ATOM 1283 CA TYR A 92 11.941 27.076 9.868 1.00 17.39 C
ATOM 1285 CB TYR A 92 11.880 28.546 10.256 1.00 16.87 C
ATOM 1288 CG TYR A 92 11.827 29.420 9.027 1.00 17.86 C
ATOM 1289 CD1 TYR A 92 12.989 29.758 8.379 1.00 16.53 C
ATOM 1291 CE1 TYR A 92 12.993 30.516 7.233 1.00 20.55 C
ATOM 1293 CZ TYR A 92 11.793 30.963 6.717 1.00 23.54 C
ATOM 1294 OH TYR A 92 11.862 31.737 5.549 1.00 25.77 O
ATOM 1296 CE2 TYR A 92 10.619 30.672 7.325 1.00 19.89 C
ATOM 1298 CD2 TYR A 92 10.626 29.840 8.507 1.00 20.04 C
ATOM 1300 C TYR A 92 12.542 26.375 11.099 1.00 14.56 C
ATOM 1301 O TYR A 92 11.856 26.154 12.042 1.00 14.48 O
ATOM 1302 N GLY A 93 13.824 26.133 11.058 1.00 13.49 N
ATOM 1304 CA GLY A 93 14.547 25.546 12.182 1.00 15.74 C
ATOM 1307 C GLY A 93 15.350 26.635 12.819 1.00 14.86 C
ATOM 1308 O GLY A 93 15.203 27.819 12.473 1.00 17.02 O
ATOM 1309 N VAL A 94 16.231 26.278 13.759 1.00 14.32 N
ATOM 1311 CA VAL A 94 16.981 27.306 14.421 1.00 14.34 C
ATOM 1313 CB VAL A 94 17.654 26.753 15.712 1.00 13.59 C
ATOM 1315 CG1 VAL A 94 18.263 27.876 16.515 1.00 13.33 C
ATOM 1319 CG2 VAL A 94 16.633 26.043 16.538 1.00 13.90 C
ATOM 1323 C VAL A 94 18.010 28.055 13.577 1.00 14.53 C
ATOM 1324 O VAL A 94 18.196 29.258 13.779 1.00 16.71 O
ATOM 1325 N ALA A 95 18.724 27.356 12.692 1.00 14.24 N
ATOM 1327 CA ALA A 95 19.859 27.839 11.990 1.00 14.00 C
ATOM 1329 CB ALA A 95 21.100 27.227 12.574 1.00 14.43 C
ATOM 1333 C ALA A 95 19.757 27.491 10.498 1.00 15.52 C
ATOM 1334 O ALA A 95 20.476 26.644 9.954 1.00 13.66 O
ATOM 1335 N PRO A 96 18.847 28.184 9.840 1.00 15.59 N
ATOM 1336 CA PRO A 96 18.487 27.876 8.443 1.00 16.93 C
ATOM 1338 CB PRO A 96 17.330 28.851 8.170 1.00 17.23 C
ATOM 1341 CG PRO A 96 17.628 29.986 9.086 1.00 16.22 C
ATOM 1344 CD PRO A 96 18.078 29.307 10.383 1.00 13.71 C
ATOM 1347 C PRO A 96 19.598 28.049 7.403 1.00 17.82 C
ATOM 1348 O PRO A 96 19.478 27.477 6.306 1.00 16.77 O
ATOM 1349 N GLN A 97 20.664 28.772 7.719 1.00 17.73 N
ATOM 1351 CA GLN A 97 21.812 28.891 6.826 1.00 18.02 C
ATOM 1353 CB GLN A 97 22.374 30.341 6.726 1.00 18.03 C
ATOM 1356 CG GLN A 97 21.509 31.218 5.783 1.00 22.97 C
ATOM 1359 CD GLN A 97 20.220 31.715 6.401 1.00 23.17 C
ATOM 1360 OE1 GLN A 97 20.303 32.467 7.345 1.00 27.41 O
ATOM 1361 NE2 GLN A 97 19.016 31.311 5.865 1.00 26.08 N
ATOM 1364 C GLN A 97 22.901 27.903 7.080 1.00 17.35 C
ATOM 1365 O GLN A 97 23.900 27.913 6.351 1.00 17.54 O
ATOM 1366 N ALA A 98 22.763 27.057 8.125 1.00 15.56 N
ATOM 1368 CA ALA A 98 23.794 26.040 8.361 1.00 16.07 C
ATOM 1370 CB ALA A 98 23.615 25.387 9.738 1.00 15.36 C
ATOM 1374 C ALA A 98 23.657 24.997 7.256 1.00 15.80 C
ATOM 1375 O ALA A 98 22.610 24.906 6.610 1.00 18.34 O
ATOM 1376 N LYS A 99 24.683 24.195 7.082 1.00 16.19 N
ATOM 1378 CA LYS A 99 24.670 23.108 6.118 1.00 15.45 C
ATOM 1380 CB LYS A 99 25.882 23.152 5.268 1.00 16.64 C
ATOM 1383 CG LYS A 99 25.789 24.264 4.222 1.00 17.86 C
ATOM 1386 CD LYS A 99 24.616 24.101 3.322 1.00 22.94 C
ATOM 1389 CE LYS A 99 24.844 25.062 2.185 1.00 28.36 C
ATOM 1392 NZ LYS A 99 23.614 25.181 1.383 1.00 28.94 N
ATOM 1396 C LYS A 99 24.604 21.759 6.887 1.00 15.54 C
ATOM 1397 O LYS A 99 25.012 21.684 8.019 1.00 15.10 O
ATOM 1398 N LEU A 100 24.136 20.742 6.185 1.00 14.73 N
ATOM 1400 CA LEU A 100 23.801 19.460 6.791 1.00 15.28 C
ATOM 1402 CB LEU A 100 22.361 19.131 6.489 1.00 14.80 C
ATOM 1405 CG LEU A 100 21.852 17.724 6.719 1.00 16.65 C
ATOM 1407 CD1 LEU A 100 21.751 17.484 8.242 1.00 17.43 C
ATOM 1411 CD2 LEU A 100 20.500 17.473 6.155 1.00 17.01 C
ATOM 1415 C LEU A 100 24.743 18.373 6.336 1.00 15.64 C
ATOM 1416 O LEU A 100 25.114 18.290 5.154 1.00 17.60 O
ATOM 1417 N TRP A 101 25.206 17.566 7.298 1.00 15.09 N
ATOM 1419 CA TRP A 101 25.895 16.350 6.942 1.00 15.10 C
ATOM 1421 CB TRP A 101 27.265 16.234 7.534 1.00 14.66 C
ATOM 1424 CG TRP A 101 28.408 17.171 7.076 1.00 13.68 C
ATOM 1425 CD1 TRP A 101 28.342 18.164 6.137 1.00 14.24 C
ATOM 1427 NE1 TRP A 101 29.575 18.741 5.956 1.00 14.73 N
ATOM 1429 CE2 TRP A 101 30.465 18.110 6.770 1.00 14.20 C
ATOM 1430 CD2 TRP A 101 29.751 17.123 7.498 1.00 15.01 C
ATOM 1431 CE3 TRP A 101 30.470 16.329 8.413 1.00 15.44 C
ATOM 1433 CZ3 TRP A 101 31.791 16.598 8.605 1.00 14.31 C
ATOM 1435 CH2 TRP A 101 32.451 17.587 7.845 1.00 15.17 C
ATOM 1437 CZ2 TRP A 101 31.780 18.363 6.977 1.00 14.09 C
ATOM 1439 C TRP A 101 24.932 15.267 7.451 1.00 16.46 C
ATOM 1440 O TRP A 101 24.830 15.022 8.675 1.00 14.81 O
ATOM 1441 N ALA A 102 24.250 14.579 6.534 1.00 14.78 N
ATOM 1443 CA ALA A 102 23.255 13.610 6.910 1.00 15.54 C
ATOM 1445 CB ALA A 102 22.086 13.639 5.973 1.00 16.18 C
ATOM 1449 C ALA A 102 23.897 12.221 6.941 1.00 15.83 C
ATOM 1450 O ALA A 102 24.187 11.661 5.898 1.00 15.17 O
ATOM 1451 N TYR A 103 24.148 11.692 8.140 1.00 14.35 N
ATOM 1453 CA TYR A 103 24.797 10.400 8.290 1.00 14.35 C
ATOM 1455 CB TYR A 103 25.985 10.493 9.225 1.00 13.92 C
ATOM 1458 CG TYR A 103 27.247 11.147 8.697 1.00 13.29 C
ATOM 1459 CD1 TYR A 103 27.275 11.938 7.550 1.00 14.70 C
ATOM 1461 CE1 TYR A 103 28.455 12.512 7.113 1.00 14.99 C
ATOM 1463 CZ TYR A 103 29.587 12.335 7.783 1.00 13.42 C
ATOM 1464 OH TYR A 103 30.820 12.886 7.417 1.00 17.55 O
ATOM 1466 CE2 TYR A 103 29.608 11.561 8.961 1.00 11.55 C
ATOM 1468 CD2 TYR A 103 28.445 10.996 9.399 1.00 12.45 C
ATOM 1470 C TYR A 103 23.813 9.419 8.860 1.00 13.70 C
ATOM 1471 O TYR A 103 23.336 9.583 9.966 1.00 13.01 O
ATOM 1472 N LYS A 104 23.490 8.383 8.101 1.00 13.67 N
ATOM 1474 CA LYS A 104 22.524 7.385 8.564 1.00 12.46 C
ATOM 1476 CB LYS A 104 21.773 6.738 7.407 1.00 14.90 C
ATOM 1479 CG LYS A 104 20.789 5.718 7.815 1.00 15.07 C
ATOM 1482 CD LYS A 104 19.991 5.144 6.616 1.00 14.19 C
ATOM 1485 CE LYS A 104 18.751 4.402 7.036 1.00 17.35 C
ATOM 1488 NZ LYS A 104 18.027 3.784 5.831 1.00 15.18 N
ATOM 1492 C LYS A 104 23.249 6.327 9.362 1.00 14.29 C
ATOM 1493 O LYS A 104 24.138 5.652 8.836 1.00 14.08 O
ATOM 1494 N VAL A 105 22.893 6.215 10.645 1.00 12.75 N
ATOM 1496 CA VAL A 105 23.513 5.287 11.592 1.00 13.70 C
ATOM 1498 CB VAL A 105 24.301 6.043 12.684 1.00 13.12 C
ATOM 1500 CG1 VAL A 105 25.244 6.961 12.010 1.00 14.29 C
ATOM 1504 CG2 VAL A 105 23.388 6.804 13.578 1.00 12.47 C
ATOM 1508 C VAL A 105 22.491 4.405 12.292 1.00 13.35 C
ATOM 1509 O VAL A 105 22.851 3.501 13.036 1.00 14.40 O
ATOM 1510 N LEU A 106 21.218 4.733 12.140 1.00 13.80 N
ATOM 1512 CA LEU A 106 20.133 3.912 12.678 1.00 15.31 C
ATOM 1514 CB LEU A 106 19.165 4.715 13.533 1.00 14.78 C
ATOM 1517 CG LEU A 106 19.820 5.395 14.752 1.00 14.84 C
ATOM 1519 CD1 LEU A 106 18.745 6.216 15.434 1.00 13.44 C
ATOM 1523 CD2 LEU A 106 20.365 4.281 15.645 1.00 13.80 C
ATOM 1527 C LEU A 106 19.328 3.395 11.488 1.00 16.71 C
ATOM 1528 O LEU A 106 19.217 4.083 10.457 1.00 14.73 O
ATOM 1529 N GLY A 107 18.812 2.184 11.617 1.00 18.94 N
ATOM 1531 CA GLY A 107 17.950 1.629 10.581 1.00 20.89 C
ATOM 1534 C GLY A 107 16.534 2.176 10.597 1.00 22.18 C
ATOM 1535 O GLY A 107 16.136 3.087 11.335 1.00 21.65 O
ATOM 1536 N ASP A 108 15.714 1.570 9.755 1.00 24.79 N
ATOM 1538 CA ASP A 108 14.419 2.139 9.442 1.00 25.79 C
ATOM 1540 CB ASP A 108 13.946 1.584 8.117 1.00 26.09 C
ATOM 1543 CG ASP A 108 14.971 1.774 7.022 1.00 28.51 C
ATOM 1544 OD1 ASP A 108 15.795 2.721 7.082 1.00 27.80 O
ATOM 1545 OD2 ASP A 108 15.020 1.038 6.025 1.00 30.77 O
ATOM 1546 C ASP A 108 13.331 1.997 10.489 1.00 26.41 C
ATOM 1547 O ASP A 108 12.229 2.535 10.294 1.00 26.78 O
ATOM 1548 N ASN A 109 13.629 1.262 11.566 1.00 26.19 N
ATOM 1550 CA ASN A 109 12.751 1.172 12.719 1.00 25.53 C
ATOM 1552 CB ASN A 109 12.399 -0.264 13.022 1.00 26.84 C
ATOM 1555 CG ASN A 109 11.599 -0.920 11.863 1.00 30.82 C
ATOM 1556 OD1 ASN A 109 10.606 -0.338 11.353 1.00 35.24 O
ATOM 1557 ND2 ASN A 109 12.038 -2.093 11.429 1.00 36.51 N
ATOM 1560 C ASN A 109 13.340 1.943 13.933 1.00 24.23 C
ATOM 1561 O ASN A 109 12.941 1.773 15.071 1.00 23.68 O
ATOM 1562 N GLY A 110 14.325 2.774 13.652 1.00 22.01 N
ATOM 1564 CA GLY A 110 14.823 3.684 14.685 1.00 20.58 C
ATOM 1567 C GLY A 110 15.783 3.001 15.656 1.00 18.79 C
ATOM 1568 O GLY A 110 15.989 3.492 16.797 1.00 18.63 O
ATOM 1569 N SER A 111 16.373 1.885 15.208 1.00 16.52 N
ATOM 1571 CA SER A 111 17.377 1.225 16.057 1.00 17.48 C
ATOM 1573 CB SER A 111 16.805 0.002 16.752 1.00 18.93 C
ATOM 1576 OG SER A 111 16.663 -1.046 15.856 1.00 20.57 O
ATOM 1578 C SER A 111 18.625 0.916 15.250 1.00 15.84 C
ATOM 1579 O SER A 111 18.585 0.814 14.022 1.00 15.08 O
ATOM 1580 N GLY A 112 19.767 0.761 15.913 1.00 15.46 N
ATOM 1582 CA GLY A 112 20.991 0.537 15.198 1.00 14.74 C
ATOM 1585 C GLY A 112 22.080 -0.033 16.063 1.00 13.99 C
ATOM 1586 O GLY A 112 21.852 -0.365 17.219 1.00 12.44 O
ATOM 1587 N TYR A 113 23.229 -0.171 15.431 1.00 13.65 N
ATOM 1589 CA TYR A 113 24.372 -0.836 16.000 1.00 14.69 C
ATOM 1591 CB TYR A 113 24.992 -1.754 14.982 1.00 14.83 C
ATOM 1594 CG TYR A 113 24.139 -2.928 14.627 1.00 16.70 C
ATOM 1595 CD1 TYR A 113 24.217 -4.098 15.339 1.00 18.38 C
ATOM 1597 CE1 TYR A 113 23.392 -5.213 14.997 1.00 18.28 C
ATOM 1599 CZ TYR A 113 22.516 -5.121 13.926 1.00 19.64 C
ATOM 1600 OH TYR A 113 21.730 -6.214 13.573 1.00 20.11 O
ATOM 1602 CE2 TYR A 113 22.465 -3.958 13.189 1.00 19.66 C
ATOM 1604 CD2 TYR A 113 23.269 -2.871 13.557 1.00 15.59 C
ATOM 1606 C TYR A 113 25.441 0.094 16.471 1.00 13.86 C
ATOM 1607 O TYR A 113 25.825 1.019 15.758 1.00 14.60 O
ATOM 1608 N SER A 114 25.880 -0.113 17.706 1.00 13.30 N
ATOM 1610 CA SER A 114 26.958 0.655 18.290 1.00 13.35 C
ATOM 1612 CB SER A 114 27.507 -0.213 19.432 1.00 15.78 C
ATOM 1615 OG SER A 114 28.722 0.270 19.995 1.00 14.15 O
ATOM 1617 C SER A 114 28.125 0.916 17.339 1.00 14.05 C
ATOM 1618 O SER A 114 28.615 2.023 17.226 1.00 13.89 O
ATOM 1619 N ASP A 115 28.581 -0.139 16.665 1.00 13.29 N
ATOM 1621 CA ASP A 115 29.724 0.014 15.754 1.00 14.72 C
ATOM 1623 CB AASP A 115 30.159 -1.299 15.125 0.50 16.85 C
ATOM 1624 CB BASP A 115 29.949 -1.288 14.969 0.50 15.71 C
ATOM 1629 CG AASP A 115 29.100 -1.900 14.308 0.50 20.25 C
ATOM 1630 CG BASP A 115 30.701 -2.324 15.752 0.50 16.91 C
ATOM 1631 OD1 AASP A 115 28.555 -1.177 13.460 0.50 32.11 O
ATOM 1632 OD1 BASP A 115 31.693 -1.951 16.379 0.50 24.07 O
ATOM 1633 OD2 AASP A 115 28.717 -3.057 14.477 0.50 33.25 O
ATOM 1634 OD2 BASP A 115 30.401 -3.501 15.764 0.50 20.69 O
ATOM 1635 C ASP A 115 29.511 1.034 14.682 1.00 13.31 C
ATOM 1636 O ASP A 115 30.488 1.671 14.268 1.00 13.00 O
ATOM 1637 N ASP A 116 28.292 1.098 14.156 1.00 12.95 N
ATOM 1639 CA ASP A 116 27.982 1.996 13.046 1.00 13.15 C
ATOM 1641 CB ASP A 116 26.618 1.685 12.446 1.00 14.36 C
ATOM 1644 CG ASP A 116 26.506 0.299 11.819 1.00 14.39 C
ATOM 1645 OD1 ASP A 116 27.509 -0.378 11.592 1.00 13.15 O
ATOM 1646 OD2 ASP A 116 25.408 -0.179 11.584 1.00 13.28 O
ATOM 1647 C ASP A 116 28.001 3.437 13.581 1.00 13.01 C
ATOM 1648 O ASP A 116 28.529 4.354 12.937 1.00 13.99 O
ATOM 1649 N ILE A 117 27.409 3.644 14.748 1.00 13.05 N
ATOM 1651 CA ILE A 117 27.404 4.952 15.339 1.00 12.04 C
ATOM 1653 CB ILE A 117 26.518 4.961 16.572 1.00 12.89 C
ATOM 1655 CG1 ILE A 117 25.034 4.744 16.168 1.00 17.41 C
ATOM 1658 CD1 ILE A 117 24.279 3.948 17.085 1.00 21.55 C
ATOM 1662 CG2 ILE A 117 26.715 6.288 17.378 1.00 15.14 C
ATOM 1666 C ILE A 117 28.813 5.403 15.623 1.00 11.86 C
ATOM 1667 O ILE A 117 29.195 6.548 15.321 1.00 12.61 O
ATOM 1668 N ALA A 118 29.609 4.532 16.227 1.00 10.45 N
ATOM 1670 CA ALA A 118 30.981 4.891 16.519 1.00 11.56 C
ATOM 1672 CB ALA A 118 31.649 3.800 17.353 1.00 11.97 C
ATOM 1676 C ALA A 118 31.786 5.248 15.273 1.00 11.35 C
ATOM 1677 O ALA A 118 32.511 6.241 15.232 1.00 10.56 O
ATOM 1678 N ALA A 119 31.597 4.459 14.253 1.00 11.09 N
ATOM 1680 CA ALA A 119 32.298 4.693 13.010 1.00 10.91 C
ATOM 1682 CB ALA A 119 32.030 3.600 12.104 1.00 11.91 C
ATOM 1686 C ALA A 119 31.875 6.029 12.430 1.00 10.50 C
ATOM 1687 O ALA A 119 32.721 6.808 11.942 1.00 12.46 O
ATOM 1688 N ALA A 120 30.589 6.342 12.539 1.00 11.95 N
ATOM 1690 CA ALA A 120 30.079 7.579 12.001 1.00 11.18 C
ATOM 1692 CB ALA A 120 28.626 7.575 12.034 1.00 11.63 C
ATOM 1696 C ALA A 120 30.643 8.813 12.743 1.00 11.63 C
ATOM 1697 O ALA A 120 31.033 9.799 12.104 1.00 11.85 O
ATOM 1698 N ILE A 121 30.708 8.753 14.070 1.00 10.33 N
ATOM 1700 CA ILE A 121 31.291 9.848 14.892 1.00 10.58 C
ATOM 1702 CB ILE A 121 31.215 9.481 16.379 1.00 11.12 C
ATOM 1704 CG1 ILE A 121 29.768 9.320 16.750 1.00 11.01 C
ATOM 1707 CD1 ILE A 121 29.566 8.668 18.128 1.00 11.36 C
ATOM 1711 CG2 ILE A 121 31.860 10.543 17.229 1.00 12.83 C
ATOM 1715 C ILE A 121 32.749 10.129 14.510 1.00 11.68 C
ATOM 1716 O ILE A 121 33.158 11.259 14.287 1.00 12.00 O
ATOM 1717 N ARG A 122 33.536 9.055 14.448 1.00 11.70 N
ATOM 1719 CA ARG A 122 34.929 9.171 14.046 1.00 13.86 C
ATOM 1721 CB ARG A 122 35.603 7.810 14.114 1.00 14.57 C
ATOM 1724 CG ARG A 122 35.715 7.320 15.531 1.00 14.77 C
ATOM 1727 CD ARG A 122 36.384 5.975 15.679 1.00 18.79 C
ATOM 1730 NE ARG A 122 36.784 5.757 17.048 1.00 21.92 N
ATOM 1732 CZ ARG A 122 37.945 6.112 17.577 1.00 22.62 C
ATOM 1733 NH1 ARG A 122 38.894 6.640 16.838 1.00 20.73 N
ATOM 1736 NH2 ARG A 122 38.178 5.850 18.857 1.00 29.11 N
ATOM 1739 C ARG A 122 35.088 9.760 12.636 1.00 14.45 C
ATOM 1740 O ARG A 122 35.992 10.563 12.389 1.00 13.33 O
ATOM 1741 N HIS A 123 34.198 9.348 11.743 1.00 12.96 N
ATOM 1743 CA HIS A 123 34.231 9.828 10.385 1.00 14.40 C
ATOM 1745 CB HIS A 123 33.324 9.001 9.522 1.00 14.46 C
ATOM 1748 CG HIS A 123 33.390 9.347 8.065 1.00 17.57 C
ATOM 1749 ND1 HIS A 123 34.358 8.843 7.224 1.00 26.34 N
ATOM 1751 CE1 HIS A 123 34.183 9.333 6.005 1.00 26.65 C
ATOM 1753 NE2 HIS A 123 33.120 10.115 6.015 1.00 23.02 N
ATOM 1755 CD2 HIS A 123 32.596 10.125 7.299 1.00 22.31 C
ATOM 1757 C HIS A 123 33.913 11.345 10.332 1.00 15.58 C
ATOM 1758 O HIS A 123 34.587 12.095 9.658 1.00 14.13 O
ATOM 1759 N VAL A 124 32.914 11.801 11.081 1.00 13.58 N
ATOM 1761 CA VAL A 124 32.701 13.233 11.195 1.00 13.94 C
ATOM 1763 CB VAL A 124 31.583 13.598 12.235 1.00 13.67 C
ATOM 1765 CG1 VAL A 124 31.476 15.111 12.408 1.00 11.98 C
ATOM 1769 CG2 VAL A 124 30.258 13.019 11.847 1.00 14.52 C
ATOM 1773 C VAL A 124 33.980 13.971 11.580 1.00 12.11 C
ATOM 1774 O VAL A 124 34.323 14.973 10.938 1.00 13.19 O
ATOM 1775 N ALA A 125 34.672 13.495 12.604 1.00 12.61 N
ATOM 1777 CA ALA A 125 35.875 14.123 13.121 1.00 12.03 C
ATOM 1779 CB ALA A 125 36.351 13.398 14.322 1.00 11.98 C
ATOM 1783 C ALA A 125 36.972 14.158 12.062 1.00 13.52 C
ATOM 1784 O ALA A 125 37.610 15.186 11.838 1.00 13.20 O
ATOM 1785 N ASP A 126 37.081 13.059 11.312 1.00 13.79 N
ATOM 1787 CA ASP A 126 38.087 12.980 10.268 1.00 15.94 C
ATOM 1789 CB ASP A 126 38.180 11.566 9.743 1.00 16.11 C
ATOM 1792 CG ASP A 126 38.895 10.635 10.677 1.00 16.70 C
ATOM 1793 OD1 ASP A 126 39.620 11.075 11.580 1.00 17.85 O
ATOM 1794 OD2 ASP A 126 38.795 9.393 10.586 1.00 17.09 O
ATOM 1795 C ASP A 126 37.736 13.933 9.133 1.00 16.71 C
ATOM 1796 O ASP A 126 38.604 14.612 8.602 1.00 17.22 O
ATOM 1797 N GLU A 127 36.465 14.027 8.798 1.00 16.48 N
ATOM 1799 CA GLU A 127 36.033 14.934 7.759 1.00 17.08 C
ATOM 1801 CB GLU A 127 34.580 14.723 7.386 1.00 17.14 C
ATOM 1804 CG GLU A 127 34.319 13.431 6.618 1.00 18.23 C
ATOM 1807 CD GLU A 127 34.875 13.485 5.205 1.00 23.17 C
ATOM 1808 OE1 GLU A 127 34.333 14.250 4.412 1.00 22.57 O
ATOM 1809 OE2 GLU A 127 35.887 12.809 4.967 1.00 25.80 O
ATOM 1810 C GLU A 127 36.256 16.370 8.204 1.00 18.24 C
ATOM 1811 O GLU A 127 36.634 17.255 7.393 1.00 17.10 O
ATOM 1812 N ALA A 128 35.969 16.626 9.465 1.00 16.20 N
ATOM 1814 CA ALA A 128 36.165 17.979 10.000 1.00 17.01 C
ATOM 1816 CB ALA A 128 35.582 18.100 11.469 1.00 18.11 C
ATOM 1820 C ALA A 128 37.607 18.403 9.959 1.00 17.06 C
ATOM 1821 O ALA A 128 37.923 19.537 9.561 1.00 18.46 O
ATOM 1822 N SER A 129 38.496 17.519 10.360 1.00 17.73 N
ATOM 1824 CA SER A 129 39.896 17.869 10.334 1.00 19.04 C
ATOM 1826 CB SER A 129 40.735 16.796 10.996 1.00 19.88 C
ATOM 1829 OG SER A 129 40.289 15.493 10.649 1.00 28.54 O
ATOM 1831 C SER A 129 40.367 18.063 8.907 1.00 18.31 C
ATOM 1832 O SER A 129 41.158 18.968 8.641 1.00 19.92 O
ATOM 1833 N ARG A 130 39.927 17.209 8.003 1.00 17.50 N
ATOM 1835 CA ARG A 130 40.418 17.258 6.611 1.00 17.79 C
ATOM 1837 CB ARG A 130 39.938 16.052 5.802 1.00 17.78 C
ATOM 1840 CG ARG A 130 40.573 15.989 4.406 1.00 17.70 C
ATOM 1843 CD ARG A 130 40.048 14.864 3.632 1.00 18.82 C
ATOM 1846 NE ARG A 130 38.768 15.271 3.064 1.00 25.15 N
ATOM 1848 CZ ARG A 130 37.641 14.760 3.393 1.00 25.02 C
ATOM 1849 NH1 ARG A 130 37.620 13.808 4.337 1.00 26.77 N
ATOM 1852 NH2 ARG A 130 36.524 15.209 2.775 1.00 23.08 N
ATOM 1855 C ARG A 130 39.990 18.543 5.958 1.00 19.20 C
ATOM 1856 O ARG A 130 40.816 19.255 5.352 1.00 20.50 O
ATOM 1857 N THR A 131 38.740 18.915 6.155 1.00 18.72 N
ATOM 1859 CA THR A 131 38.127 20.089 5.461 1.00 19.43 C
ATOM 1861 CB THR A 131 36.673 19.866 5.244 1.00 20.43 C
ATOM 1863 OG1 THR A 131 35.973 19.754 6.517 1.00 18.62 O
ATOM 1865 CG2 THR A 131 36.421 18.548 4.449 1.00 22.94 C
ATOM 1869 C THR A 131 38.262 21.415 6.203 1.00 20.40 C
ATOM 1870 O THR A 131 37.906 22.461 5.657 1.00 20.95 O
ATOM 1871 N GLY A 132 38.758 21.356 7.431 1.00 18.57 N
ATOM 1873 CA GLY A 132 38.841 22.513 8.289 1.00 19.51 C
ATOM 1876 C GLY A 132 37.464 23.129 8.581 1.00 20.63 C
ATOM 1877 O GLY A 132 37.313 24.336 8.829 1.00 23.12 O
ATOM 1878 N SER A 133 36.442 22.287 8.646 1.00 18.55 N
ATOM 1880 CA SER A 133 35.094 22.754 8.904 1.00 18.11 C
ATOM 1882 CB SER A 133 34.080 21.819 8.260 1.00 18.42 C
ATOM 1885 OG SER A 133 34.242 21.666 6.844 1.00 21.03 O
ATOM 1887 C SER A 133 34.768 22.836 10.427 1.00 16.26 C
ATOM 1888 O SER A 133 35.348 22.145 11.284 1.00 15.54 O
ATOM 1889 N LYS A 134 33.798 23.687 10.720 1.00 16.27 N
ATOM 1891 CA LYS A 134 33.275 23.830 12.096 1.00 15.54 C
ATOM 1893 CB LYS A 134 32.921 25.274 12.419 1.00 15.50 C
ATOM 1896 CG LYS A 134 34.154 26.176 12.525 1.00 18.18 C
ATOM 1899 CD LYS A 134 33.819 27.647 12.502 1.00 25.94 C
ATOM 1902 CE LYS A 134 35.064 28.567 12.191 1.00 30.57 C
ATOM 1905 NZ LYS A 134 36.391 28.051 12.564 1.00 34.14 N
ATOM 1909 C LYS A 134 32.032 22.951 12.094 1.00 13.21 C
ATOM 1910 O LYS A 134 31.121 23.177 11.349 1.00 14.18 O
ATOM 1911 N VAL A 135 32.015 21.919 12.921 1.00 12.06 N
ATOM 1913 CA VAL A 135 30.964 20.957 12.863 1.00 12.02 C
ATOM 1915 CB VAL A 135 31.487 19.632 12.321 1.00 13.28 C
ATOM 1917 CG1 VAL A 135 30.363 18.596 12.114 1.00 14.27 C
ATOM 1921 CG2 VAL A 135 32.322 19.867 11.006 1.00 14.42 C
ATOM 1925 C VAL A 135 30.383 20.673 14.241 1.00 11.74 C
ATOM 1926 O VAL A 135 31.097 20.566 15.220 1.00 11.76 O
ATOM 1927 N VAL A 136 29.071 20.604 14.286 1.00 11.28 N
ATOM 1929 CA VAL A 136 28.389 20.206 15.478 1.00 10.73 C
ATOM 1931 CB VAL A 136 27.285 21.177 15.819 1.00 11.25 C
ATOM 1933 CG1 VAL A 136 26.576 20.755 17.127 1.00 13.78 C
ATOM 1937 CG2 VAL A 136 27.897 22.594 16.013 1.00 12.65 C
ATOM 1941 C VAL A 136 27.702 18.852 15.159 1.00 11.22 C
ATOM 1942 O VAL A 136 26.973 18.747 14.178 1.O0 11.53 O
ATOM 1943 N ILE A 137 27.928 17.850 15.993 1.00 9.65 N
ATOM 1945 CA ILE A 137 27.255 16.573 15.854 1.00 10.61 C
ATOM 1947 CB ILE A 137 28.113 15.459 16.381 1.00 9.23 C
ATOM 1949 CG1 ILE A 137 29.215 1.5121 15.395 1.00 11.83 C
ATOM 1952 CD1 ILE A 137 30.266 14.104 15.930 1.00 11.56 C
ATOM 1956 CG2 ILE A 137 27.238 14.230 16.611 1.00 10.38 C
ATOM 1960 C ILE A 137 25.993 16.610 16.690 1.00 10.44 C
ATOM 1961 O ILE A 137 26.031 1.7014 17.869 1.00 11.92 O
ATOM 1962 N ASN A 138 24.899 16.203 16.096 1.00 9.00 N
ATOM 1964 CA ASN A 138 23.654 15.942 16.764 1.00 10.52 C
ATOM 1966 CB ASN A 138 22.494 16.601 15.996 1.00 8.55 C
ATOM 1969 CG ASN A 138 21.146 16.503 16.715 1.00 12.38 C
ATOM 1970 OD1 ASN A 138 20.648 17.515 17.236 1.00 10.74 O
ATOM 1971 ND2 ASN A 138 20.519 15.297 16.722 1.00 9.55 N
ATOM 1974 C ASN A 138 23.376 14.477 16.861 1.00 10.74 C
ATOM 1975 O ASN A 138 23.256 13.799 15.833 1.00 9.80 O
ATOM 1976 N MET A 139 23.208 13.987 18.091 1.00 9.89 N
ATOM 1978 CA MET A 139 22.830 12.585 18.304 1.00 10.28 C
ATOM 1980 CB MET A 139 23.975 11.764 18.906 1.00 9.62 C
ATOM 1983 CG MET A 139 24.984 11.345 17.895 1.00 8.67 C
ATOM 1986 SD MET A 139 26.240 10.206 18.525 1.00 11.34 S
ATOM 1987 CE MET A 139 27.161 11.324 19.556 1.00 13.56 C
ATOM 1991 C MET A 139 21.581 12.474 19.162 1.00 10.20 C
ATOM 1992 O MET A 139 21.587 12.497 20.413 1.00 9.22 O
ATOM 1993 N SER A 140 20.467 12.424 18.458 1.00 10.57 N
ATOM 1995 CA SER A 140 19.166 12.207 19.083 1.00 10.10 C
ATOM 1997 CB SER A 140 18.082 12.817 18.201 1.00 10.22 C
ATOM 2000 OG SER A 140 18.142 14.229 18.264 1.00 11.42 O
ATOM 2002 C SER A 140 18.959 10.705 19.255 1.00 11.04 C
ATOM 2003 O SER A 140 18.006 10.119 18.716 1.00 10.43 O
ATOM 2004 N LEU A 141 19.844 10.063 20.011 1.00 10.62 N
ATOM 2006 CA LEU A 141 19.890 8.627 20.116 1.00 10.50 C
ATOM 2008 CB LEU A 141 20.446 8.014 18.833 1.00 10.74 C
ATOM 2011 CG LEU A 141 21.881 8.483 18.439 1.00 11.49 C
ATOM 2013 CD1 LEU A 141 22.939 7.897 19.316 1.00 11.20 C
ATOM 2017 CD2 LEU A 141 22.119 8.057 17.001 1.00 12.54 C
ATOM 2021 C LEU A 141 20.748 8.223 21.297 1.00 9.69 C
ATOM 2022 O LEU A 141 21.402 9.060 21.892 1.00 9.38 O
ATOM 2023 N GLY A 142 20.640 6.975 21.689 1.00 11.48 N
ATOM 2025 CA GLY A 142 21.450 6.472 22.789 1.00 10.69 C
ATOM 2028 C GLY A 142 21.046 5.146 23.335 1.00 9.74 C
ATOM 2029 O GLY A 142 20.283 4.413 22.660 1.00 12.20 O
ATOM 2030 N SER A 143 21.517 4.850 24.562 1.00 11.68 N
ATOM 2032 CA SER A 143 21.200 3.610 25.308 1.00 11.10 C
ATOM 2034 CB SER A 143 22.187 2.489 25.050 1.00 11.52 C
ATOM 2037 OG SER A 143 23.517 2.918 25.316 1.00 11.14 O
ATOM 2039 C SER A 143 21.272 3.995 26.777 1.00 12.09 C
ATOM 2040 O SER A 143 21.941 4.966 27.161 1.00 11.62 O
ATOM 2041 N SER A 144 20.523 3.292 27.587 1.00 11.90 N
ATOM 2043 CA SER A 144 20.527 3.552 28.992 1.00 11.92 C
ATOM 2045 CB SER A 144 19.513 2.623 29.653 1.00 13.61 C
ATOM 2048 OG SER A 144 19.521 2.848 31.017 1.00 18.36 O
ATOM 2050 C SER A 144 21.903 3.622 9.593 1.00 13.78 C
ATOM 2051 O SER A 144 22.341 4.161 30.401 1.00 14.05 O
ATOM 2052 N ALA A 145 22.551 2.278 29.189 1.00 12.68 N
ATOM 2054 CA ALA A 145 23.892 1.972 29.678 1.00 11.54 C
ATOM 2056 CB ALA A 145 24.135 0.503 29.488 1.00 12.43 C
ATOM 2060 C ALA A 145 24.956 2.745 28.886 1.00 12.26 C
ATOM 2061 O ALA A 145 24.814 3.001 27.712 1.00 12.18 O
ATOM 2062 N LYS A 146 26.067 3.066 29.521 1.00 10.71 N
ATOM 2064 CA LYS A 146 27.184 3.640 28.760 1.00 11.08 C
ATOM 2066 CB LYS A 146 28.219 4.095 29.754 1.00 10.62 C
ATOM 2069 CG LYS A 146 29.563 4.535 29.197 1.00 13.37 C
ATOM 2072 CD LYS A 146 30.506 5.206 30.245 1.00 14.55 C
ATOM 2075 CE LYS A 146 31.796 5.638 29.643 1.00 17.59 C
ATOM 2078 NZ LYS A 146 32.732 6.238 30.665 1.00 17.20 N
ATOM 2082 C LYS A 146 27.767 2.559 27.834 1.00 8.93 C
ATOM 2083 O LYS A 146 27.978 1.383 28.241 1.00 11.42 O
ATOM 2084 N ASP A 147 28.075 2.956 26.621 1.00 10.15 N
ATOM 2086 CA ASP A 147 28.694 2.129 25.575 1.00 10.08 C
ATOM 2088 CB ASP A 147 27.843 2.189 24.296 1.00 10.84 C
ATOM 2091 CG ASP A 147 28.460 1.509 23.117 1.00 11.61 C
ATOM 2092 OD1 ASP A 147 29.701 1.630 22.895 1.00 11.69 O
ATOM 2093 OD2 ASP A 147 27.753 0.879 22.305 1.00 10.96 O
ATOM 2094 C ASP A 147 30.057 2.784 25.353 1.00 10.79 C
ATOM 2095 O ASP A 147 30.163 3.902 24.859 1.00 9.34 O
ATOM 2096 N SER A 148 31.104 2.055 25.717 1.00 9.95 N
ATOM 2098 CA SER A 148 32.450 2.588 25.641 1.00 11.43 C
ATOM 2100 CB SER A 148 33.431 1.838 26.533 1.00 11.86 C
ATOM 2103 OG SER A 148 33.164 2.051 27.904 1.00 13.07 O
ATOM 2105 C SER A 148 32.999 2.765 24.221 1.00 12.17 C
ATOM 2106 O SER A 148 33.958 3.537 24.021 1.00 10.72 O
ATOM 2107 N LEU A 149 32.471 1.997 23.269 1.00 9.59 N
ATOM 2109 CA LEU A 149 32.936 2.120 21.909 1.00 10.95 C
ATOM 2111 CB LEU A 149 32.374 1.029 21.030 1.00 11.13 C
ATOM 2114 CG LEU A 149 32.863 1.087 19.569 1.00 13.82 C
ATOM 2116 CD1 LEU A 149 34.404 0.961 19.536 1.00 14.72 C
ATOM 2120 CD2 LEU A 149 32.162 0.036 18.699 1.00 15.05 C
ATOM 2124 C LEU A 149 32.474 3.511 21.419 1.00 10.85 C
ATOM 2125 O LEU A 149 33.201 4.268 20.807 1.00 10.58 O
ATOM 2126 N ILE A 150 31.223 3.823 21.649 1.00 9.24 N
ATOM 2128 CA ILE A 150 30.671 5.127 21.255 1.00 9.06 C
ATOM 2130 CB ILE A 150 29.145 5.136 21.471 1.00 8.95 C
ATOM 2132 CG1 ILE A 150 28.499 4.376 20.337 1.00 9.94 C
ATOM 2135 CD1 ILE A 150 27.038 4.154 20.508 1.00 11.53 C
ATOM 2139 CG2 ILE A 150 28.601 6.553 21.538 1.00 11.45 C
ATOM 2143 C ILE A 150 31.433 6.226 22.052 1.00 7.79 C
ATOM 2144 O ILE A 150 31.793 7.297 21.500 1.00 8.15 O
ATOM 2145 N ALA A 151 31.724 5.956 23.300 1.00 8.34 N
ATOM 2147 CA ALA A 151 32.396 6.930 24.152 1.00 9.35 C
ATOM 2149 CB ALA A 151 32.479 6.402 25.577 1.00 10.22 C
ATOM 2153 C ALA A 151 33.796 7.240 23.629 1.00 9.49 C
ATOM 2154 O ALA A 151 34.215 8.422 23.583 1.00 9.45 O
ATOM 2155 N SER A 152 34.508 6.177 23.181 1.00 10.40 N
ATOM 2157 CA SER A 152 35.823 6.371 22.613 1.00 11.13 C
ATOM 2159 CB SER A 152 36.466 5.047 22.278 1.00 10.46 C
ATOM 2162 OG SER A 152 37.628 5.216 21.460 1.00 13.86 O
ATOM 2164 C SER A 152 35.737 7.285 21.349 1.00 11.17 C
ATOM 2165 O SER A 152 36.585 8.207 21.144 1.00 11.47 O
ATOM 2166 N ALA A 153 34.688 7.103 20.578 1.00 11.26 N
ATOM 2168 CA ALA A 153 34.476 7.917 19.358 1.00 11.23 C
ATOM 2170 CB ALA A 153 33.413 7.295 18.527 1.00 12.05 C
ATOM 2174 C ALA A 153 34.143 9.349 19.699 1.00 11.53 C
ATOM 2175 O ALA A 153 34.699 10.314 19.103 1.00 11.12 O
ATOM 2176 N VAL A 154 33.285 9.529 20.695 1.00 9.67 N
ATOM 2178 CA VAL A 154 32.941 10.878 21.104 1.00 9.77 C
ATOM 2180 CB VAL A 154 31.908 10.810 22.223 1.00 10.26 C
ATOM 2182 CG1 VAL A 154 31.833 12.136 22.988 1.00 12.19 C
ATOM 2186 CG2 VAL A 154 30.583 10.402 21.661 1.00 11.04 C
ATOM 2190 C VAL A 154 34.229 11.606 21.565 1.00 11.02 C
ATOM 2191 O VAL A 154 34.449 12.779 21.212 1.00 11.61 O
ATOM 2192 N ASP A 155 35.069 10.954 22.367 1.00 10.47 N
ATOM 2194 CA ASP A 155 36.309 11.603 22.838 1.00 12.38 C
ATOM 2196 CB ASP A 155 37.040 10.744 23.859 1.00 13.32 C
ATOM 2199 CG ASP A 155 36.328 10.668 25.183 1.00 19.66 C
ATOM 2200 OD1 ASP A 155 35.449 11.508 25.455 1.00 21.98 O
ATOM 2201 OD2 ASP A 155 36.604 9.813 26.030 1.00 21.73 O
ATOM 2202 C ASP A 155 37.242 11.932 21.674 1.00 13.46 C
ATOM 2203 O ASP A 155 37.928 12.926 21.695 1.00 12.65 O
ATOM 2204 N TYR A 156 37.308 11.034 20.694 1.00 12.30 N
ATOM 2206 CA TYR A 156 38.119 11.263 19.510 1.00 11.91 C
ATOM 2208 CB TYR A 156 37.992 10.073 18.607 1.00 12.85 C
ATOM 2211 CG TYR A 156 38.753 10.140 17.309 1.00 13.57 C
ATOM 2212 CD1 TYR A 156 40.154 9.965 17.286 1.00 16.30 C
ATOM 2214 CE1 TYR A 156 40.822 9.989 16.093 1.00 15.71 C
ATOM 2216 CZ TYR A 156 40.136 10.172 14.899 1.00 20.85 C
ATOM 2217 OH TYR A 156 40.795 10.142 13.677 1.00 19.47 O
ATOM 2219 CE2 TYR A 156 38.771 10.352 14.883 1.00 14.75 C
ATOM 2221 CD2 TYR A 156 38.096 10.349 16.111 1.00 14.20 C
ATOM 2223 C TYR A 156 37.653 12.497 18.764 1.00 11.70 C
ATOM 2224 O TYR A 156 38.463 13.343 18.408 1.00 12.40 O
ATOM 2225 N ALA A 157 36.332 12.649 18.630 1.00 11.59 N
ATOM 2227 CA ALA A 157 35.773 13.776 17.895 1.00 10.92 C
ATOM 2229 CB ALA A 157 34.319 13.493 17.547 1.00 11.98 C
ATOM 2233 C ALA A 157 35.926 15.058 18.670 1.00 11.69 C
ATOM 2234 O ALA A 157 36.214 16.117 18.072 1.00 11.27 O
ATOM 2235 N TYR A 158 35.740 14.996 19.983 1.00 11.31 N
ATOM 2237 CA TYR A 158 35.855 l6.210 20.809 1.00 12.56 C
ATOM 2239 CB TYR A 158 35.410 15.940 22.243 1.00 12.28 C
ATOM 2242 CG TYR A 158 35.147 17.188 23.090 1.00 9.96 C
ATOM 2243 CD1 TYR A 158 34.015 17.937 22.878 1.00 11.56 C
ATOM 2245 CE1 TYR A 158 33.754 19.051 23.629 1.00 13.20 C
ATOM 2247 CZ TYR A 158 34.635 19.477 24.580 1.00 13.62 C
ATOM 2248 OH TYR A 158 34.370 20.612 25.295 1.00 12.22 O
ATOM 2250 CE2 TYR A 158 35.813 18.809 24.787 1.00 13.48 C
ATOM 2252 CD2 TYR A 158 36.078 17.647 24.028 1.00 12.56 C
ATOM 2254 C TYR A 158 37.308 16.655 20.783 1.00 12.48 C
ATOM 2255 O TYR A 158 37.591 17.853 20.822 1.00 12.68 O
ATOM 2256 N GLY A 159 38.207 15.683 20.642 1.00 12.38 N
ATOM 2258 CA GLY A 159 39.628 15.978 20.651 1.00 13.17 C
ATOM 2261 C GLY A 159 40.055 16.611 19.371 1.00 13.46 C
ATOM 2262 O GLY A 159 41.161 17.165 19.297 1.00 14.28 O
ATOM 2263 N LYS A 160 39.238 16.495 18.350 1.00 12.48 N
ATOM 2265 CA LYS A 160 39.486 17.099 17.035 1.00 14.66 C
ATOM 2267 CB LYS A 160 39.324 16.046 15.953 1.00 15.36 C
ATOM 2270 CG LYS A 160 40.421 14.964 15.992 1.00 20.16 C
ATOM 2273 CD LYS A 160 40.057 13.848 15.058 1.00 25.00 C
ATOM 2276 CE LYS A 160 41.183 13.408 14.161 1.00 31.38 C
ATOM 2279 NZ LYS A 160 41.602 14.404 13.204 1.00 30.54 N
ATOM 2283 C LYS A 160 38.603 18.344 16.761 1.00 14.03 C
ATOM 2284 O LYS A 160 38.469 18.786 15.621 1.00 12.37 O
ATOM 2285 N GLY A 161 38.076 18.954 17.829 1.00 13.97 N
ATOM 2287 CA GLY A 161 37.363 20.230 17.751 1.00 13.11 C
ATOM 2290 C GLY A 161 35.928 20.180 17.281 1.00 12.99 C
ATOM 2291 O GLY A 161 35.434 21.185 16.743 1.00 14.25 O
ATOM 2292 N VAL A 162 35.269 19.020 17.395 1.00 11.44 N
ATOM 2294 CA VAL A 162 33.858 18.848 16.972 1.00 10.32 C
ATOM 2296 CB VAL A 162 33.621 17.492 16.309 1.00 11.03 C
ATOM 2298 CG1 VAL A 162 32.146 17.268 15.950 1.00 11.59 C
ATOM 2302 CG2 VAL A 162 34.438 17.378 15.034 1.00 13.60 C
ATOM 2306 C VAL A 162 32.991 18.918 18.219 1.00 10.43 C
ATOM 2307 O VAL A 162 33.306 18.259 19.222 1.00 11.54 O
ATOM 2308 N LEU A 163 31.965 19.748 18.217 1.00 9.11 N
ATOM 2310 CA LEU A 163 31.075 19.817 19.382 1.00 10.40 C
ATOM 2312 CB LEU A 163 30.278 21.105 19.344 1.00 11.53 C
ATOM 2315 CG LEU A 163 29.336 21.334 20.515 1.00 10.22 C
ATOM 2317 CD1 LEU A 163 30.163 21.561 21.748 1.00 12.89 C
ATOM 2321 CD2 LEU A 163 28.486 22.497 20.248 1.00 13.67 C
ATOM 2325 C LEU A 163 30.118 18.647 19.257 1.00 10.89 C
ATOM 2326 O LEU A 163 29.620 18.367 18.176 1.00 13.34 O
ATOM 2327 N ILE A 164 29.832 17.975 20.347 1.00 11.01 N
ATOM 2329 CA ILE A 164 28.860 16.890 20.383 1.00 9.92 C
ATOM 2331 CB ILE A 164 29.500 15.573 20.908 1.00 10.24 C
ATOM 2333 CG1 ILE A 164 30.616 15.070 19.976 1.00 13.39 C
ATOM 2336 CD1 ILE A 164 31.893 15.389 20.491 1.00 16.69 C
ATOM 2340 CG2 ILE A 164 28.496 14.458 20.907 1.00 12.88 C
ATOM 2344 C ILE A 164 27.673 17.259 21.275 1.00 10.29 C
ATOM 2345 O ILE A 164 27.851 17.505 22.479 1.00 10.17 O
ATOM 2346 N VAL A 165 26.489 17.191 20.694 1.00 9.19 N
ATOM 2348 CA VAL A 165 25.257 17.479 21.391 1.00 9.03 C
ATOM 2350 CB VAL A 165 24.576 18.708 20.753 1.00 10.21 C
ATOM 2352 CG1 VAL A 165 23.300 19.053 21.542 1.00 9.33 C
ATOM 2356 CG2 VAL A 165 25.483 19.888 20.715 1.00 11.01 C
ATOM 2360 C VAL A 165 24.360 16.245 21.311 1.00 8.47 C
ATOM 2361 O VAL A 165 24.193 15.681 20.222 1.00 10.40 O
ATOM 2362 N ALA A 166 23.833 15.747 22.452 1.00 9.28 N
ATOM 2364 CA ALA A 166 23.163 14.469 22.484 1.00 8.57 C
ATOM 2366 CB ALA A 166 24.104 13.327 22.794 1.00 9.70 C
ATOM 2370 C ALA A 166 22.011 14.454 23.489 1.00 9.40 C
ATOM 2371 O ALA A 166 22.028 15.186 24.476 1.00 9.37 O
ATOM 2372 N ALA A 167 21.000 13.646 23.186 1.00 10.21 N
ATOM 2374 CA ALA A 167 19.794 13.637 23.965 1.00 10.10 C
ATOM 2376 CB ALA A 167 18.747 12.726 23.251 1.00 11.66 C
ATOM 2380 C ALA A 167 20.086 13.087 25.329 1.00 10.38 C
ATOM 2381 O ALA A 167 20.787 12.038 25.431 1.00 8.93 O
ATOM 2382 N ALA A 168 19.424 13.572 26.360 1.00 10.36 N
ATOM 2384 CA ALA A 168 19.623 13.036 27.685 1.00 10.56 C
ATOM 2386 CB ALA A 168 19.014 13.978 28.698 1.00 11.45 C
ATOM 2390 C ALA A 168 19.026 11.631 27.894 1.00 10.08 C
ATOM 2391 O ALA A 168 19.441 10.860 28.771 1.00 10.97 O
ATOM 2392 N GLY A 169 18.020 11.315 27.108 1.00 9.80 N
ATOM 2394 CA GLY A 169 17.216 10.125 27.318 1.00 9.88 C
ATOM 2397 C GLY A 169 15.777 10.485 27.780 1.00 11.11 C
ATOM 2398 O GLY A 169 15.483 11.623 28.208 1.00 10.34 O
ATOM 2399 N ASN A 170 14.882 9.492 27.676 1.00 11.54 N
ATOM 2401 CA ASN A 170 13.483 9.636 28.090 1.00 11.53 C
ATOM 2403 CB ASN A 170 12.579 9.382 26.872 1.00 11.78 C
ATOM 2406 CG ASN A 170 12.911 10.285 25.682 1.00 13.65 C
ATOM 2407 OD1 ASN A 170 13.358 11.427 25.856 1.00 14.26 O
ATOM 2408 ND2 ASN A 170 12.666 9.791 24.465 1.00 10.92 N
ATOM 2411 C ASN A 170 13.116 8.658 29.184 1.00 12.69 C
ATOM 2412 O ASN A 170 12.046 8.036 29.123 1.00 12.66 O
ATOM 2413 N SER A 171 13.989 8.483 30.170 1.00 12.61 N
ATOM 2415 CA SER A 171 13.754 7.487 31.223 1.00 13.48 C
ATOM 2417 CB SER A 171 15.025 6.692 31.423 1.00 14.78 C
ATOM 2420 OG SER A 171 15.277 5.967 30.233 1.00 13.11 O
ATOM 2422 C SER A 171 13.308 8.147 32.538 1.00 13.22 C
ATOM 2423 O SER A 171 13.429 7.526 33.583 1.00 14.40 O
ATOM 2424 N GLY A 172 12.811 9.371 32.496 1.00 14.32 N
ATOM 2426 CA GLY A 172 12.428 10.098 33.710 1.00 14.13 C
ATOM 2429 C GLY A 172 11.127 9.606 34.292 1.00 15.66 C
ATOM 2430 O GLY A 172 10.473 8.814 33.614 1.00 15.22 O
ATOM 2431 N SER A 173 10.681 10.13 435424 1.00 14.94 N
ATOM 2433 CA SER A 173 11.269 11.278 36.134 1.00 16.57 C
ATOM 2435 CB SER A 173 10.144 12.174 36.639 1.00 17.91 C
ATOM 2438 OG SER A 173 9.3841 11.435 376.07 1.00 18.04 O
ATOM 2440 C SER A 173 12.196 10.908 37.265 1.00 16.47 C
ATOM 2441 O SER A 173 12.751 11.790 37.970 1.00 15.55 O
ATOM 2442 N GLY A 174 12.476 9.615 37.359 1.00 15.06 N
ATOM 2444 CA GLY A 174 13.318 9.075 38.400 1.00 16.35 C
ATOM 2447 C GLY A 174 14.715 9.629 38.233 1.00 17.64 C
ATOM 2448 O GLY A 174 15.159 9.906 37.086 1.00 17.46 O
ATOM 2449 N SER A 175 15.404 9.827 39.351 1.00 17.08 N
ATOM 2451 CA SER A 175 16.752 10.404 39.336 1.00 18.22 C
ATOM 2453 CB SER A 175 17.129 10.794 40.759 1.00 19.80 C
ATOM 2456 OG SER A 175 16.121 11.654 41.308 1.00 21.20 O
ATOM 2458 C SER A 175 17.783 9.457 38.777 1.00 16.85 C
ATOM 2459 O SER A 175 17.638 8.238 38.884 1.00 15.37 O
ATOM 2460 N ASN A 176 18.838 10.010 38.168 1.00 16.57 N
ATOM 2462 CA ASN A 176 19.966 9.230 37.675 1.00 15.32 C
ATOM 2464 CB ASN A 176 20.679 8.475 38.817 1.00 17.33 C
ATOM 2467 CG ASN A 176 22.174 8.352 38.565 1.00 20.64 C
ATOM 2468 OD1 ASN A 176 22.676 9.003 37.649 1.00 19.65 O
ATOM 2469 ND2 ASN A 176 22.881 7.508 39.336 1.00 23.68 N
ATOM 2472 C ASN A 176 19.634 8.250 36.592 1.00 15.22 C
ATOM 2473 O ASN A 176 20.208 7.146 36.528 1.00 16.86 O
ATOM 2474 N THR A 177 18.718 8.639 35.723 1.00 14.53 N
ATOM 2476 CA THR A 177 18.299 7.815 34.612 1.00 14.30 C
ATOM 2478 CB THR A 177 16.768 7.831 34.488 1.00 13.61 C
ATOM 2480 OG1 THR A 177 16.255 9.161 34.632 1.00 12.76 O
ATOM 2482 CG2 THR A 177 16.053 7.001 35.629 1.00 14.89 C
ATOM 2486 C THR A 177 18.907 8.265 33.267 1.00 13.62 C
ATOM 2487 O THR A 177 18.555 7.704 32.213 1.00 14.34 O
ATOM 2488 N ILE A 178 19.736 9.305 33.324 1.00 12.33 N
ATOM 2490 CA ILE A 178 20.436 9.809 32.125 1.00 10.85 C
ATOM 2492 CB ILE A 178 21.473 10.886 32.543 1.00 11.28 C
ATOM 2494 CG1 ILE A 178 22.118 11.576 31.337 1.00 11.95 C
ATOM 2497 CD1 ILE A 178 22.981 12.833 31.722 1.00 12.82 C
ATOM 2501 CG2 ILE A 178 22.550 10.300 33.406 1.00 11.10 C
ATOM 2505 C ILE A 178 21.057 8.663 31.350 1.00 10.78 C
ATOM 2506 O ILE A 178 21.582 7.715 31.950 1.00 10.96 O
ATOM 2507 N GLY A 179 20.973 8.706 30.032 1.00 9.07 N
ATOM 2509 CA GLY A 179 21.658 7.732 29.200 1.00 10.43 C
ATOM 2512 C GLY A 179 22.842 8.334 28.433 1.00 10.17 C
ATOM 2513 O GLY A 179 23.302 9.423 28.716 1.00 9.05 O
ATOM 2514 N PHE A 180 23.302 7.579 27.474 1.00 10.42 N
ATOM 2516 CA PHE A 180 24.566 7.766 26.771 1.00 9.90 C
ATOM 2518 CB PHE A 180 25.597 6.710 27.248 1.00 11.20 C
ATOM 2521 CG PHE A 180 25.926 6.868 28.691 1.00 10.40 C
ATOM 2522 CD1 PHE A 180 25.089 6.304 29.673 1.00 12.43 C
ATOM 2524 CE1 PHE A 180 25.346 6.539 31.013 1.00 13.80 C
ATOM 2526 CZ PHE A 180 26.377 7.353 31.379 1.00 14.77 C
ATOM 2528 CE2 PHE A 180 27.195 7.936 30.428 1.00 14.15 C
ATOM 2530 CD2 PHE A 180 26.951 7.710 29.086 1.00 12.50 C
ATOM 2532 C PHE A 180 24.307 7.663 25.268 1.00 10.49 C
ATOM 2533 O PHE A 180 23.545 6.804 24.833 1.00 11.55 O
ATOM 2534 N PRO A 181 25.023 8.448 24.458 1.00 9.50 N
ATOM 2535 CA PRO A 181 26.196 9.246 24.890 1.00 9.13 C
ATOM 2537 CB PRO A 181 26.937 9.496 23.524 1.00 9.24 C
ATOM 2540 CG PRO A 181 25.855 9.591 22.649 1.00 11.31 C
ATOM 2543 CD PRO A 181 24.874 8.496 23.002 1.00 10.03 C
ATOM 2546 C PRO A 181 25.983 10.570 25.610 1.00 10.79 C
ATOM 2547 O PRO A 181 26.959 11.251 25.986 1.00 9.76 O
ATOM 2548 N GLY A 182 24.743 11.019 25.752 1.00 10.07 N
ATOM 2550 CA GLY A 182 24.480 12.260 26.450 1.00 10.91 C
ATOM 2553 C GLY A 182 25.260 12.460 27.748 1.00 10.65 C
ATOM 2554 O GLY A 182 25.843 13.532 27.983 1.00 10.24 O
ATOM 2555 N GLY A 183 25.246 11.400 28.570 1.00 10.23 N
ATOM 2557 CA GLY A 183 25.860 11.370 29.888 1.00 11.34 C
ATOM 2560 C GLY A 183 27.370 11.393 29.929 1.00 11.75 C
ATOM 2561 O GLY A 183 27.957 11.394 31.025 1.00 10.33 O
ATOM 2562 N LEU A 184 28.007 11.351 28.761 1.00 11.62 N
ATOM 2564 CA LEU A 184 29.474 11.436 28.718 1.00 11.77 C
ATOM 2566 CB LEU A 184 30.022 11.038 27.369 1.00 10.76 C
ATOM 2569 CG LEU A 184 29.612 9.640 26.946 1.00 13.28 C
ATOM 2571 CD1 LEU A 184 29.958 9.447 25.484 1.00 13.01 C
ATOM 2575 CD2 LEU A 184 30.306 8.563 27.839 1.00 15.87 C
ATOM 2579 C LEU A 184 29.966 12.827 29.034 1.00 11.00 C
ATOM 2580 O LEU A 184 29.321 13.827 28.682 1.00 10.77 O
ATOM 2581 N VAL A 185 31.180 12.922 29.584 1.00 11.17 N
ATOM 2583 CA VAL A 185 31.673 14.225 29.979 1.00 10.77 C
ATOM 2585 CB VAL A 185 32.994 14.115 30.811 1.00 13.00 C
ATOM 2587 CG1 VAL A 185 33.978 13.569 30.013 1.00 16.83 C
ATOM 2591 CG2 VAL A 185 33.500 15.504 31.144 1.00 16.03 C
ATOM 2595 C VAL A 185 31.868 15.172 28.842 1.00 9.95 C
ATOM 2596 O VAL A 185 31.683 16.370 28.972 1.00 10.97 O
ATOM 2597 N ASN A 186 32.181 14.614 27.684 1.00 10.43 N
ATOM 2599 CA ASN A 186 32.483 15.376 26.517 1.00 11.79 C
ATOM 2601 CB ASN A 186 33.763 14.865 25.836 1.00 13.55 C
ATOM 2604 CG ASN A 186 35.029 15.152 26.660 1.00 14.82 C
ATOM 2605 OD1 ASN A 186 35.093 16.110 27.370 1.00 19.19 O
ATOM 2606 ND2 ASN A 186 36.021 14.326 26.517 1.00 21.64 N
ATOM 2609 C ASN A 186 31.305 15.525 25.536 1.00 11.85 C
ATOM 2610 O ASN A 186 31.485 15.915 24.384 1.00 11.39 O
ATOM 2611 N ALA A 187 30.108 15.138 25.977 1.00 10.51 N
ATOM 2613 CA ALA A 187 28.904 15.382 25.179 1.00 11.08 C
ATOM 2615 CB ALA A 187 28.189 14.150 24.848 1.00 11.19 C
ATOM 2619 C ALA A 187 27.984 16.317 25.975 1.00 10.66 C
ATOM 2620 O ALA A 187 27.878 16.147 27.186 1.00 11.05 O
ATOM 2621 N VAL A 188 27.318 17.248 25.288 1.00 9.26 N
ATOM 2623 CA VAL A 188 26.326 18.148 25.895 1.00 9.21 C
ATOM 2625 CB VAL A 188 26.120 19.418 25.046 1.00 9.41 C
ATOM 2627 CG1 VAL A 188 25.035 20.249 25.661 1.00 7.57 C
ATOM 2631 CG2 VAL A 188 27.448 20.164 24.893 1.00 10.01 C
ATOM 2635 C VAL A 188 24.996 17.346 25.984 1.00 9.78 C
ATOM 2636 O VAL A 188 24.349 17.137 24.959 1.00 10.45 O
ATOM 2637 N ALA A 189 24.572 16.989 27.200 1.00 8.67 N
ATOM 2639 CA ALA A 189 23.325 16.236 27.430 1.00 9.35 C
ATOM 2641 CB ALA A 189 23.379 15.510 28.763 1.00 10.27 C
ATOM 2645 C ALA A 189 22.197 17.214 27.451 1.00 8.43 C
ATOM 2646 O ALA A 189 22.179 18.183 28.238 1.00 9.35 O
ATOM 2647 N VAL A 190 21.182 16.948 26.651 1.00 9.14 N
ATOM 2649 CA VAL A 190 20.084 17.882 26.554 1.00 8.32 C
ATOM 2651 CB VAL A 190 19.843 18.296 25.119 1.00 8.58 C
ATOM 2653 CG1 VAL A 190 18.731 19.309 25.052 1.00 11.50 C
ATOM 2657 CG2 VAL A 190 21.084 18.873 24.482 1.00 9.20 C
ATOM 2661 C VAL A 190 18.791 17.317 27.087 1.00 9.51 C
ATOM 2662 O VAL A 190 18.340 16.256 26.625 1.00 9.51 O
ATOM 2663 N ALA A 191 18.236 17.973 28.093 1.00 9.50 N
ATOM 2665 CA ALA A 191 16.934 17.559 28.685 1.00 10.18 C
ATOM 2667 CB ALA A 191 16.868 18.057 30.134 1.00 8.69 C
ATOM 2671 C ALA A 191 15.800 18.184 27.900 1.00 10.24 C
ATOM 2672 O ALA A 191 16.007 19.182 27.249 1.00 10.28 O
ATOM 2673 N ALA A 192 14.570 17.659 28.021 1.00 11.22 N
ATOM 2675 CA ALA A 192 13.428 18.171 27.272 1.00 11.79 C
ATOM 2677 CB ALA A 192 12.593 17.012 26.728 1.00 13.73 C
ATOM 2681 C ALA A 192 12.499 19.027 28.134 1.00 11.54 C
ATOM 2682 O ALA A 192 12.048 18.549 29.179 1.00 11.30 O
ATOM 2683 N LEU A 193 12.222 20.238 27.673 1.00 11.58 N
ATOM 2685 CA LEU A 193 11.194 21.103 28.258 1.00 11.55 C
ATOM 2687 CB LEU A 193 11.519 22.561 28.037 1.00 12.06 C
ATOM 2690 CG LEU A 193 12.844 23.095 28.613 1.00 10.40 C
ATOM 2692 CD1 LEU A 193 13.137 24.484 28.211 1.00 9.32 C
ATOM 2696 CD2 LEU A 193 12.752 22.903 30.081 1.00 13.29 C
ATOM 2700 C LEU A 193 9.852 20.802 27.577 1.00 14.05 C
ATOM 2701 O LEU A 193 9.814 20.460 26.414 1.00 13.73 O
ATOM 2702 N GLU A 194 8.755 21.004 28.305 1.00 13.56 N
ATOM 2704 CA GLU A 194 7.422 21.049 27.647 1.00 13.63 C
ATOM 2706 CB GLU A 194 6.472 20.125 28.359 1.00 12.74 C
ATOM 2709 CG GLU A 194 6.320 20.410 29.837 1.00 16.62 C
ATOM 2712 CD GLU A 194 5.490 19.404 30.603 1.00 19.10 C
ATOM 2713 OE1 GLU A 194 5.288 18.280 30.118 1.00 20.53 O
ATOM 2714 OE2 GLU A 194 5.153 19.744 31.765 1.00 17.20 O
ATOM 2715 C GLU A 194 6.934 22.460 27.699 1.00 14.48 C
ATOM 2716 O GLU A 194 7.502 23.275 28.431 1.00 13.32 O
ATOM 2717 N ASN A 195 5.862 22.778 26.954 1.00 14.74 N
ATOM 2719 CA ASN A 195 5.416 24.169 26.857 1.00 15.00 C
ATOM 2721 CB ASN A 195 4.773 24.467 25.479 1.00 16.14 C
ATOM 2724 CG ASN A 195 4.612 25.970 25.198 1.00 16.46 C
ATOM 2725 OD1 ASN A 195 5.236 26.803 25.855 1.00 14.84 O
ATOM 2726 ND2 ASN A 195 3.775 26.318 24.208 1.00 13.91 N
ATOM 2729 C ASN A 195 4.439 24.440 27.945 1.00 16.03 C
ATOM 2730 O ASN A 195 3.256 24.692 27.662 1.00 15.98 O
ATOM 2731 N VAL A 196 4.904 24.381 29.170 1.00 16.13 N
ATOM 2733 CA VAL A 196 4.106 24.623 30.344 1.00 16.89 C
ATOM 2735 CB VAL A 196 3.739 23.348 31.019 1.00 18.38 C
ATOM 2737 CG1 VAL A 196 3.058 23.613 32.326 1.00 20.19 C
ATOM 2741 CG2 VAL A 196 2.922 22.415 30.070 1.00 18.32 C
ATOM 2745 C VAL A 196 4.991 25.380 31.307 1.00 17.79 C
ATOM 2746 O VAL A 196 6.215 25.147 31.344 1.00 17.15 O
ATOM 2747 N GLN A 197 4.410 26.305 32.055 1.00 17.34 N
ATOM 2749 CA GLN A 197 5.171 27.048 33.060 1.00 16.33 C
ATOM 2751 CB GLN A 197 4.838 28.518 33.012 1.00 16.74 C
ATOM 2754 CG GLN A 197 4.987 29.169 31.720 1.00 16.89 C
ATOM 2757 CD GLN A 197 6.455 29.357 31.343 1.00 18.48 C
ATOM 2758 OE1 GLN A 197 7.216 30.009 32.096 1.00 14.66 O
ATOM 2759 NE2 GLN A 197 6.850 28.769 30.223 1.00 15.37 N
ATOM 2762 C GLN A 197 4.907 26.538 34.467 1.00 17.79 C
ATOM 2763 O GLN A 197 3.778 26.114 34.825 1.00 18.50 O
ATOM 2764 N GLN A 198 5.977 26.409 35.232 1.00 17.07 N
ATOM 2766 CA GLN A 198 5.879 25.977 36.627 1.00 17.39 C
ATOM 2768 CB GLN A 198 5.865 24.485 36.778 1.00 17.84 C
ATOM 2771 CG GLN A 198 5.744 24.058 38.164 1.00 18.38 C
ATOM 2774 CD GLN A 198 5.797 22.558 38.413 1.00 25.24 C
ATOM 2775 OE1 GLN A 198 6.612 21.813 37.815 1.00 26.03 O
ATOM 2776 NE2 GLN A 198 4.927 22.090 39.323 1.00 29.00 N
ATOM 2779 C GLN A 198 6.998 26.623 37.362 1.00 17.51 C
ATOM 2780 O GLN A 198 8.156 26.681 36.904 1.00 16.23 O
ATOM 2781 N ASN A 199 6.655 27.147 38.520 1.00 18.31 N
ATOM 2783 CA ASN A 199 7.612 27.890 39.321 1.00 19.42 C
ATOM 2785 CB ASN A 199 8.676 26.953 39.915 1.00 19.53 C
ATOM 2788 CG ASN A 199 8.107 25.949 40.861 1.00 24.01 C
ATOM 2789 OD1 ASN A 199 7.226 26.254 41.691 1.00 23.71 O
ATOM 2790 ND2 ASN A 199 8.598 24.738 40.769 1.00 25.09 N
ATOM 2793 C ASN A 199 8.285 29.018 38.592 1.00 20.51 C
ATOM 2794 O ASN A 199 9.491 29.356 38.863 1.00 20.07 O
ATOM 2795 N GLY A 200 7.533 29.653 37.712 1.00 19.65 N
ATOM 2797 CA GLY A 200 8.005 30.820 36.991 1.00 20.16 C
ATOM 2800 C GLY A 200 8.883 30.609 35.774 1.00 19.26 C
ATOM 2801 O GLY A 200 9.347 31.577 35.177 1.00 18.58 O
ATOM 2802 N THR A 201 9.091 29.348 35.384 1.00 17.29 N
ATOM 2804 CA THR A 201 9.876 29.045 34.196 1.00 16.82 C
ATOM 2806 CB THR A 201 11.327 28.563 34.596 1.00 16.41 C
ATOM 2808 OG1 THR A 201 11.309 27.246 35.174 1.00 17.63 O
ATOM 2810 CG2 THR A 201 11.954 29.437 35.622 1.00 17.27 C
ATOM 2814 C THR A 201 9.248 27.935 33.389 1.00 15.50 C
ATOM 2815 O THR A 201 8.267 27.356 33.817 1.00 14.83 O
ATOM 2816 N TYR A 202 9.845 27.608 32.230 1.00 15.66 N
ATOM 2818 CA TYR A 202 9.469 26.407 31.571 1.00 14.51 C
ATOM 2820 CB TYR A 202 10.308 26.183 30.300 1.00 15.38 C
ATOM 2823 CG TYR A 202 9.853 27.053 29.177 1.00 12.00 C
ATOM 2824 CD1 TYR A 202 8.775 26.682 28.359 1.00 12.96 C
ATOM 2826 CE1 TYR A 202 8.344 27.510 27.364 1.00 13.55 C
ATOM 2828 CZ TYR A 202 8.995 28.682 27.157 1.00 12.70 C
ATOM 2829 OH TYR A 202 8.586 29.559 26.172 1.00 14.68 O
ATOM 2831 CE2 TYR A 202 10.027 29.063 27.961 1.00 14.77 C
ATOM 2833 CD2 TYR A 202 10.441 28.245 28.957 1.00 13.26 C
ATOM 2835 C TYR A 202 9.637 25.229 32.488 1.00 14.45 C
ATOM 2836 O TYR A 202 10.44 22.523 13.415 1.00 14.03 O
ATOM 2837 N ARG A 203 8.894 24.168 32.206 1.00 14.53 N
ATOM 2839 CA ARG A 203 8.939 22.971 32.988 1.00 13.25 C
ATOM 2841 CB ARG A 203 7.454 22.543 33.262 1.00 14.52 C
ATOM 2844 CG ARG A 203 7.315 21.347 34.102 1.00 14.19 C
ATOM 2847 CD ARG A 203 5.795 21.083 34.523 1.00 15.99 C
ATOM 2850 NE ARG A 203 5.730 20.106 35.572 1.00 17.45 N
ATOM 2852 CZ ARG A 203 5.729 18.806 35.402 1.00 17.33 C
ATOM 2853 NH1 ARG A 203 5.762 18.306 34.191 1.00 15.77 N
ATOM 2856 NH2 ARG A 203 5.741 17.996 36.447 1.00 18.53 N
ATOM 2859 C ARG A 203 9.595 21.805 32.251 1.00 12.75 C
ATOM 2860 O ARG A 203 9.285 21.570 31.076 1.00 12.82 O
ATOM 2861 N VAL A 204 10.505 21.090 32.907 1.00 12.18 N
ATOM 2863 CA VAL A 204 11.043 19.877 32.378 1.00 11.32 C
ATOM 2865 CB VAL A 204 12.141 19.338 33.296 1.00 11.73 C
ATOM 2867 CG1 VAL A 204 12.765 18.035 32.735 1.00 11.27 C
ATOM 2871 CG2 VAL A 204 13.229 20.373 33.437 1.00 12.71 C
ATOM 2875 C VAL A 204 9.925 18.831 32.221 1.00 12.28 C
ATOM 2876 O VAL A 204 9.172 18.549 33.185 1.00 12.08 O
ATOM 2877 N ALA A 205 9.855 18.166 31.063 1.00 12.11 N
ATOM 2879 CA ALA A 205 8.882 17.061 30.935 1.00 12.63 C
ATOM 2881 CB ALA A 205 8.725 16.612 29.473 1.00 14.20 C
ATOM 2885 C ALA A 205 9.205 15.894 31.835 1.00 14.44 C
ATOM 2886 O ALA A 205 10.338 15.546 32.067 1.00 12.72 O
ATOM 2887 N ASP A 206 8.160 15.251 32.353 1.00 12.46 N
ATOM 2889 CA ASP A 206 8.351 14.138 33.226 1.00 14.42 C
ATOM 2891 CB ASP A 206 7.015 13.579 33.660 1.00 15.15 C
ATOM 2894 CG ASP A 206 6.273 14.456 34.620 1.00 20.28 C
ATOM 2895 OD1 ASP A 206 6.717 15.552 35.015 1.00 16.78 O
ATOM 2896 OD2 ASP A 206 5.164 14.025 35.032 1.00 21.17 O
ATOM 2897 C ASP A 206 9.161 13.020 32.556 1.00 13.89 C
ATOM 2898 O ASP A 206 9.920 12.348 33.229 1.00 15.04 O
ATOM 2899 N PHE A 207 9.016 12.821 31.246 1.00 11.78 N
ATOM 2901 CA PHE A 207 9.710 11.721 30.612 1.00 13.96 C
ATOM 2903 CB PHE A 207 9.163 11.360 29.213 1.00 13.87 C
ATOM 2906 CG PHE A 207 9.290 12.439 28.191 1.00 14.05 C
ATOM 2907 CD1 PHE A 207 10.521 12.704 27.630 1.00 13.46 C
ATOM 2909 CE1 PHE A 207 10.677 13.677 26.709 1.00 14.99 C
ATOM 2911 CZ PHE A 207 9.577 14.463 26.305 1.00 12.88 C
ATOM 2913 CE2 PHE A 207 8.325 14.173 26.841 1.00 15.57 C
ATOM 2915 CD2 PHE A 207 8.199 13.191 27.787 1.00 14.48 C
ATOM 2917 C PHE A 207 11.220 11.917 30.546 1.00 12.81 C
ATOM 2918 O PHE A 207 11.950 10.945 30.339 1.00 12.43 O
ATOM 2919 N SER A 208 11.670 13.163 30.626 1.00 13.24 N
ATOM 2921 CA SER A 208 13.099 13.459 30.389 1.00 12.69 C
ATOM 2923 CB SER A 208 13.277 14.980 30.333 1.00 13.69 C
ATOM 2926 OG SER A 208 14.593 15.399 30.016 1.00 11.00 O
ATOM 2928 C SER A 208 13.997 12.799 31.432 1.00 11.85 C
ATOM 2929 O SER A 208 13.726 12.841 32.612 1.00 12.56 O
ATOM 2930 N SER A 209 15.095 12.168 31.001 1.00 11.34 N
ATOM 2932 CA SER A 209 15.961 11.503 31.941 1.00 12.26 C
ATOM 2934 CB SER A 209 17.003 10.655 31.240 1.00 10.68 C
ATOM 2937 OG SER A 209 16.442 9.566 30.515 1.00 11.25 O
ATOM 2939 C SER A 209 16.666 12.506 32.852 1.00 11.42 C
ATOM 2940 O SER A 209 17.108 13.568 32.420 1.00 12.21 O
ATOM 2941 N ARG A 210 16.797 12.128 34.107 1.00 13.04 N
ATOM 2943 CA ARG A 210 17.480 12.973 35.089 1.00 12.02 C
ATOM 2945 CB ARG A 210 16.783 12.925 36.439 1.00 11.62 C
ATOM 2948 CG ARG A 210 15.644 13.914 36.659 1.00 10.95 C
ATOM 2951 CD ARG A 210 14.531 13.936 35.593 1.00 12.61 C
ATOM 2954 NE ARG A 210 13.496 14.936 35.948 1.00 13.59 N
ATOM 2956 CZ ARG A 210 12.450 15.250 35.214 1.00 14.23 C
ATOM 2957 NH1 ARG A 210 12.267 14.655 34.035 1.00 14.26 N
ATOM 2960 NH2 ARG A 210 11.550 16.168 35.652 1.00 13.18 N
ATOM 2963 C ARG A 210 18.906 12.544 35.328 1.00 11.40 C
ATOM 2964 O ARG A 210 19.201 11.401 35.281 1.00 12.42 O
ATOM 2965 N GLY A 211 19.756 13.520 35.625 1.00 13.31 N
ATOM 2967 CA GLY A 211 21.140 13.289 35.977 1.00 11.79 C
ATOM 2970 C GLY A 211 21.263 12.757 37.395 1.00 13.79 C
ATOM 2971 O GLY A 211 20.286 12.467 38.054 1.00 13.33 O
ATOM 2972 N ASN A 212 22.508 12.644 37.831 1.00 12.68 N
ATOM 2974 CA ASN A 212 22.852 12.132 39.139 1.00 13.86 C
ATOM 2976 CB ASN A 212 24.300 11.647 39.062 1.00 14.05 C
ATOM 2979 CG ASN A 212 24.801 11.076 40.380 1.00 15.77 C
ATOM 2980 OD1 ASN A 212 24.034 10.961 41.330 1.00 20.22 O
ATOM 2981 ND2 ASN A 212 26.057 10.638 40.402 1.00 21.14 N
ATOM 2984 C ASN A 212 22.711 13.289 40.154 1.00 13.72 C
ATOM 2985 O ASN A 212 23.466 14.254 40.141 1.00 13.40 O
ATOM 2986 N PRO A 213 21.803 13.173 41.121 1.00 14.98 N
ATOM 2987 CA PRO A 213 21.672 14.248 42.125 1.00 16.29 C
ATOM 2989 CB PRO A 213 20.586 13.722 43.065 1.00 17.58 C
ATOM 2992 CG PRO A 213 19.803 12.803 42.224 1.00 16.96 C
ATOM 2995 CD PRO A 213 20.863 12.072 41.386 1.00 15.73 C
ATOM 2998 C PRO A 213 22.966 14.577 42.864 1.00 16.46 C
ATOM 2999 O PRO A 213 23.194 15.766 43.089 1.00 18.16 O
ATOM 3000 N ALA A 214 23.809 13.573 43.084 1.00 17.81 N
ATOM 3002 CA ALA A 214 25.058 13.706 43.843 1.00 18.79 C
ATOM 3004 CB ALA A 214 25.746 12.336 44.004 1.00 19.37 C
ATOM 3008 C ALA A 214 26.022 14.653 43.188 1.00 18.92 C
ATOM 3009 O ALA A 214 26.872 15.225 43.890 1.00 17.86 O
ATOM 3010 N THR A 215 25.899 14.879 41.869 1.00 17.03 N
ATOM 3012 CA THR A 215 26.868 15.751 41.205 1.00 16.66 C
ATOM 3014 CB THR A 215 27.741 14.942 40.212 1.00 18.38 C
ATOM 3016 OG1 THR A 215 26.907 14.218 39.271 1.00 15.43 O
ATOM 3018 CG2 THR A 215 28.532 13.928 40.970 1.00 18.05 C
ATOM 3022 C THR A 215 26.278 16.952 40.479 1.00 16.40 C
ATOM 3023 O THR A 215 26.955 17.636 39.745 1.00 16.41 O
ATOM 3024 N ALA A 216 25.035 17.244 40.773 1.00 14.91 N
ATOM 3026 CA ALA A 216 24.408 18.446 40.249 1.00 16.14 C
ATOM 3028 CB ALA A 216 22.944 18.182 39.938 1.00 16.49 C
ATOM 3032 C ALA A 216 24.479 19.548 41.271 1.00 17.73 C
ATOM 3033 O ALA A 216 24.240 19.279 42.445 1.00 21.27 O
ATOM 3034 N GLY A 217 24.699 20.763 40.840 1.00 16.83 N
ATOM 3036 CA GLY A 217 24.701 21.920 41.725 1.00 17.35 C
ATOM 3039 C GLY A 217 25.994 22.704 41.603 1.00 18.14 C
ATOM 3040 O GLY A 217 26.068 23.906 41.983 1.00 19.91 O
ATOM 3041 N ASP A 218 27.007 22.103 41.001 1.00 17.40 N
ATOM 3043 CA ASP A 218 28.294 22.767 40.941 1.00 16.68 C
ATOM 3045 CB ASP A 218 29.346 21.732 41.259 1.00 17.36 C
ATOM 3048 CG ASP A 218 29.393 20.585 40.244 1.00 20.24 C
ATOM 3049 OD1 ASP A 218 28.520 20.437 39.333 1.00 17.05 O
ATOM 3050 OD2 ASP A 218 30.286 19.734 40.356 1.00 20.78 O
ATOM 3051 C ASP A 218 28.648 23.526 39.664 1.00 15.65 C
ATOM 3052 O ASP A 218 29.638 24.231 39.613 1.00 15.75 O
ATOM 3053 N TYR A 219 27.756 23.522 38.689 1.00 15.41 N
ATOM 3055 CA TYR A 219 28.003 24.099 37.380 1.00 13.99 C
ATOM 3057 CB TYR A 219 27.987 25.607 37.463 1.00 14.94 C
ATOM 3060 CG TYR A 219 26.611 26.197 37.674 1.00 15.83 C
ATOM 3061 CD1 TYR A 219 25.642 26.086 36.702 1.00 12.98 C
ATOM 3063 CE1 TYR A 219 24.385 26.648 36.871 1.00 12.57 C
ATOM 3065 CZ TYR A 219 24.125 27.301 38.052 1.00 18.74 C
ATOM 3066 OH TYR A 219 22.947 27.921 38.286 1.00 18.11 O
ATOM 3068 CE2 TYR A 219 25.090 27.438 39.021 1.00 19.74 C
ATOM 3070 CD2 TYR A 219 26.309 26.869 38.843 1.00 19.78 C
ATOM 3072 C TYR A 219 29.346 23.584 36.756 1.00 14.17 C
ATOM 3073 O TYR A 219 29.978 24.283 35.984 1.00 14.67 O
ATOM 3074 N ILE A 220 29.676 22.330 37.031 1.00 13.56 N
ATOM 3076 CA ILE A 220 30.775 21.624 36.414 1.00 15.58 C
ATOM 3078 CB ILE A 220 31.961 21.438 37.355 1.00 15.45 C
ATOM 3080 CG1 ILE A 220 32.502 22.809 37.761 1.00 20.96 C
ATOM 3083 CD1 ILE A 220 33.397 22.711 39.015 1.00 23.15 C
ATOM 3087 CG2 ILE A 220 33.087 20.625 36.671 1.00 18.47 C
ATOM 3091 C ILE A 220 30.227 20.278 35.956 1.00 13.00 C
ATOM 3092 O ILE A 220 29.633 19.505 36.691 1.00 12.94 O
ATOM 3093 N ILE A 221 30.482 19.995 34.684 1.00 15.43 N
ATOM 3095 CA ILE A 221 29.934 18.782 34.088 1.00 13.93 C
ATOM 3097 CB ILE A 221 29.793 18.960 32.541 1.00 12.79 C
ATOM 3099 CG1 ILE A 221 28.733 19.979 32.164 1.00 12.82 C
ATOM 3102 CD1 ILE A 221 27.361 19.711 32.673 1.00 12.70 C
ATOM 3106 CG2 ILE A 221 29.513 17.651 31.889 1.00 14.76 C
ATOM 3110 C ILE A 221 30.836 17.584 34.406 1.00 14.63 C
ATOM 3111 O ILE A 221 32.059 17.583 34.006 1.00 14.50 O
ATOM 3112 N GLN A 222 30.246 16.602 35.097 1.00 13.31 N
ATOM 3114 CA GLN A 222 30.786 15.267 35.285 1.00 14.28 C
ATOM 3116 CB GLN A 222 30.772 14.858 36.759 1.00 16.33 C
ATOM 3119 CG GLN A 222 31.775 15.669 37.602 1.00 18.83 C
ATOM 3122 CD GLN A 222 31.204 16.936 38.223 1.00 21.01 C
ATOM 3123 OE1 GLN A 222 29.998 17.058 38.469 1.00 22.83 O
ATOM 3124 NE2 GLN A 222 32.089 17.874 38.517 1.00 23.39 N
ATOM 3127 C GLN A 222 29.935 14.289 34.460 1.00 14.17 C
ATOM 3128 O GLN A 222 28.921 14.664 33.874 1.00 12.09 O
ATOM 3129 N GLU A 223 30.438 13.079 34.313 1.00 13.56 N
ATOM 3131 CA GLU A 223 29.646 12.052 33.675 1.00 14.32 C
ATOM 3133 CB GLU A 223 30.455 10.767 33.682 1.00 14.62 C
ATOM 3136 CG GLU A 223 29.787 9.618 329.84 1.00 15.34 C
ATOM 3139 CD GLU A 223 30.759 8.474 32.706 1.00 16.41 C
ATOM 3140 OE1 GLU A 223 31.400 8.407 31.648 1.00 19.83 O
ATOM 3141 OE2 GLU A 223 30.808 7.645 33.564 1.00 19.76 O
ATOM 3142 C GLU A 223 28.315 11.911 34.451 1.00 12.77 C
ATOM 3143 O GLU A 223 28.294 11.981 35.679 1.00 13.97 O
ATOM 3144 N ARG A 224 27.210 11.785 33.700 1.00 11.67 N
ATOM 3146 CA ARG A 224 25.834 11.585 34.178 1.00 11.39 C
ATOM 3148 CB ARG A 224 25.730 10.549 35.305 1.00 12.52 C
ATOM 3151 CG ARG A 224 26.269 9.156 349.60 1.00 16.20 C
ATOM 3154 CD ARG A 224 25.988 8.116 36.088 1.00 19.39 C
ATOM 3157 NE ARG A 224 24.589 7.737 36.052 1.00 19.97 N
ATOM 3159 CZ ARG A 224 24.123 6.785 35.271 1.00 23.20 C
ATOM 3160 NH1 ARG A 224 24.939 6.070 34.516 1.00 22.67 N
ATOM 3163 NH2 ARG A 224 22.835 6530 35.234 1.00 20.20 N
ATOM 3166 C ARG A 224 25.199 12.934 34.600 1.00 11.27 C
ATOM 3167 O ARG A 224 24.137 12.954 35.247 1.00 12.76 O
ATOM 3168 N ASP A 225 25.779 14.065 34.167 1.00 10.64 N
ATOM 3170 CA ASP A 225 25.141 15.322 34.440 1.00 11.57 C
ATOM 3172 CB ASP A 225 26.137 16.421 34.763 1.00 12.18 C
ATOM 3175 CG ASP A 225 26.783 16.290 36.115 1.00 11.47 C
ATOM 3176 OD1 ASP A 225 26.396 15.431 36.930 1.00 12.63 O
ATOM 3177 OD2 ASP A 225 27.738 17.024 36.366 1.00 12.98 O
ATOM 3178 C ASP A 225 24.386 15.833 33.187 1.00 11.72 C
ATOM 3179 O ASP A 225 24.880 15.761 32.028 1.00 10.65 O
ATOM 3180 N ILE A 226 23.195 16.366 33.428 1.00 10.89 N
ATOM 3182 CA ILE A 226 22.449 17089 32.399 1.00 10.95 C
ATOM 3184 CB ILE A 226 20.988 17.379 32.826 1.00 10.97 C
ATOM 3186 CG1 ILE A 226 20.296 16.066 33.224 1.00 8.65 C
ATOM 3189 CD1 ILE A 226 20.064 15192 32.004 1.00 12.39 C
ATOM 3193 CG2 ILE A 226 20.260 18.217 31.828 1.00 12.31 C
ATOM 3197 C ILE A 226 23.117 18.428 32.195 1.00 8.74 C
ATOM 3198 O ILE A 226 23.561 19.076 33.123 1.00 10.81 O
ATOM 3199 N GLU A 227 23.254 18.849 30.971 1.00 9.24 N
ATOM 3201 CA GLU A 227 23.902 20.150 30.715 1.00 9.53 C
ATOM 3203 CB GLU A 227 24.905 19.979 29.553 1.00 8.94 C
ATOM 3206 CG GLU A 227 25.869 21.131 29.345 1.00 9.79 C
ATOM 3209 CD GLU A 227 27.217 20.634 28.789 1.00 11.40 C
ATOM 3210 OE1 GLU A 227 27.527 19.431 28.857 1.00 8.56 O
ATOM 3211 OE2 GLU A 227 27.953 21.441 28.255 1.00 11.05 O
ATOM 3212 C GLU A 227 22.936 21.331 30.450 1.00 9.10 C
ATOM 3213 O GLU A 227 23.053 22.402 31.074 1.00 10.35 O
ATOM 3214 N VAL A 228 21.984 21.152 29.553 1.00 8.61 N
ATOM 3216 CA VAL A 228 21.094 22.222 29.176 1.00 7.54 C
ATOM 3218 CB VAL A 228 21.567 23.010 27.946 1.00 5.96 C
ATOM 3220 CG1 VAL A 228 22.834 23.726 28.263 1.00 8.28 C
ATOM 3224 CG2 VAL A 228 21.680 22.127 26.740 1.00 8.08 C
ATOM 3228 C VAL A 228 19.727 21.575 28.904 1.00 7.83 C
ATOM 3229 O VAL A 228 19.663 20.362 28.747 1.00 9.43 O
ATOM 3230 N SER A 229 18.716 22.426 28.809 1.00 10.13 N
ATOM 3232 CA SER A 229 17.369 22.024 28.520 1.00 9.88 C
ATOM 3234 CB SER A 229 16.457 22.371 29.674 1.00 10.86 C
ATOM 3237 OG SER A 229 16.811 21.670 30.827 1.00 11.90 O
ATOM 3239 C SER A 229 16.865 22.806 27.305 1.00 11.07 C
ATOM 3240 O SER A 229 17.290 23.949 27.065 1.00 11.59 O
ATOM 3241 N ALA A 230 15.964 22.167 26.536 1.00 10.22 N
ATOM 3243 CA ALA A 230 15.337 22.824 25.379 1.00 9.98 C
ATOM 3245 CB ALA A 230 16.245 22.786 24.202 1.00 11.98 C
ATOM 3249 C ALA A 230 14.001 22.181 25.011 1.00 10.40 C
ATOM 3250 O ALA A 230 13.639 21.143 25.539 1.00 11.74 O
ATOM 3251 N PRO A 231 13.241 22.873 24.162 1.00 12.52 N
ATOM 3252 CA PRO A 231 11.915 22.369 23.794 1.00 11.45 C
ATOM 3254 CB PRO A 231 11.440 23.308 22.676 1.00 12.82 C
ATOM 3257 CG PRO A 231 12.076 24.609 23.005 1.00 12.47 C
ATOM 3260 CD PRO A 231 13.518 24.184 23.540 1.00 12.90 C
ATOM 3263 C PRO A 231 11.967 20.969 23.241 1.00 10.90 C
ATOM 3264 O PRO A 231 12.689 20.713 22.238 1.00 11.39 O
ATOM 3265 N GLY A 232 11.194 20.071 23.863 1.00 11.69 N
ATOM 3267 CA GLY A 232 11.218 18.675 23.478 1.00 12.12 C
ATOM 3270 C GLY A 232 9.857 17.972 23.431 1.00 14.63 C
ATOM 3271 O GLY A 232 9.814 16.852 22.976 1.00 17.38 O
ATOM 3272 N ALA A 233 8.775 18.641 23.807 1.00 13.80 N
ATOM 3274 CA ALA A 233 7.441 17.975 23.841 1.00 15.69 C
ATOM 3276 CB ALA A 233 6.812 18.002 25.228 1.00 15.50 C
ATOM 3280 C ALA A 233 6.565 18.649 22.794 1.00 15.70 C
ATOM 3281 O ALA A 233 6.479 19.892 22.725 1.00 15.71 O
ATOM 3282 N SER A 234 6.008 17.837 21.901 1.00 15.70 N
ATOM 3284 CA SER A 234 5.123 18.323 20.820 1.00 17.34 C
ATOM 3286 CB SER A 234 3.816 18.866 21.396 1.00 19.34 C
ATOM 3289 OG SER A 234 3.151 17.862 22.071 1.00 24.09 O
ATOM 3291 C SER A 234 5.746 19.302 19.869 1.00 16.08 C
ATOM 3292 O SER A 234 5.311 20.419 19.727 1.00 16.37 O
ATOM 3293 N VAL A 235 6.816 18.859 19.244 1.00 13.70 N
ATOM 3295 CA VAL A 235 7.597 19.607 18.309 1.00 13.30 C
ATOM 3297 CB VAL A 235 9.124 19.358 18.536 1.00 11.29 C
ATOM 3299 CG1 VAL A 235 9.948 19.994 17.533 1.00 11.79 C
ATOM 3303 CG2 VAL A 235 9.475 19.925 19.919 1.00 13.78 C
ATOM 3307 C VAL A 235 7.284 19.242 16.876 1.00 14.46 C
ATOM 3308 O VAL A 235 7.529 18.141 16.413 1.00 15.04 O
ATOM 3309 N GLU A 236 6.773 20.208 16.151 1.00 15.81 N
ATOM 3311 CA GLU A 236 6.539 20.075 14.717 1.00 15.96 C
ATOM 3313 CB GLU A 236 5.419 21.059 14.323 1.00 16.03 C
ATOM 3316 CG GLU A 236 5.033 21.028 12.863 1.00 18.99 C
ATOM 3319 CD GLU A 236 3.833 21.939 12.549 1.00 22.94 C
ATOM 3320 OE1 GLU A 236 3.422 22.715 13.457 1.00 20.60 O
ATOM 3321 OE2 GLU A 236 3.255 21.772 11.420 1.00 20.10 O
ATOM 3322 C GLU A 236 7.751 20.349 13.881 1.00 16.01 C
ATOM 3323 O GLU A 236 8.534 21.272 14.139 1.00 17.39 O
ATOM 3324 N SER A 237 8.023 19.462 12.905 1.00 14.14 N
ATOM 3326 CA SER A 237 9.105 19.655 12.025 1.00 14.47 C
ATOM 3328 CB SER A 237 10.410 19.109 12.632 1.00 11.88 C
ATOM 3331 OG SER A 237 11.513 19.504 11.921 1.00 11.55 O
ATOM 3333 C SER A 237 8.819 18.900 10.715 1.00 14.97 C
ATOM 3334 O SER A 237 7.699 18.345 10.543 1.00 16.60 O
ATOM 3335 N THR A 238 9.838 18.892 9.886 1.00 15.64 N
ATOM 3337 CA THR A 238 9.851 18.230 8.581 1.00 17.00 C
ATOM 3339 CB THR A 238 11.090 18.559 7.844 1.00 18.10 C
ATOM 3341 OG1 THR A 238 12.267 18.454 8.677 1.00 16.55 O
ATOM 3343 CG2 THR A 238 11.152 19.996 7.339 1.00 16.33 C
ATOM 3347 C THR A 238 9.752 16.703 8.759 1.00 19.28 C
ATOM 3348 O THR A 238 10.213 16.169 9.768 1.00 18.16 O
ATOM 3349 N TRP A 239 9.203 16.032 7.739 1.00 19.48 N
ATOM 3351 CA TRP A 239 8.933 14.587 7.765 1.00 18.83 C
ATOM 3353 CB TRP A 239 7.503 14.322 8.122 1.00 19.25 C
ATOM 3356 CG TRP A 239 7.182 12.954 8.642 1.00 19.71 C
ATOM 3357 CD1 TRP A 239 6.343 12.009 8.085 1.00 23.51 C
ATOM 3359 NE1 TRP A 239 6.263 10.907 8.899 1.00 22.49 N
ATOM 3361 CE2 TRP A 239 7.081 11.114 9.985 1.00 21.32 C
ATOM 3362 CD2 TRP A 239 7.651 12.400 9.853 1.00 20.74 C
ATOM 3363 CE3 TRP A 239 8.529 12.864 10.851 1.00 18.32 C
ATOM 3365 CZ3 TRP A 239 8.751 12.055 11.962 1.00 21.08 C
ATOM 3367 CH2 TRP A 239 8.166 10.788 12.061 1.00 20.53 C
ATOM 3369 CZ2 TRP A 239 7.349 10.289 11.079 1.00 22.21 C
ATOM 3371 C TRP A 239 9.325 13.931 6.461 1.00 17.68 C
ATOM 3372 O TRP A 239 9.417 14.577 5.423 1.00 19.48 O
ATOM 3373 N TYR A 240 9.679 12.642 6.550 1.00 17.80 N
ATOM 3375 CA TYR A 240 10.332 11.1947 5.485 1.00 17.76 C
ATOM 3377 CB TYR A 240 10.862 10.568 5.938 1.00 20.08 C
ATOM 3380 CG TYR A 240 9.864 9.469 6.036 1.00 17.92 C
ATOM 3381 CD1 TYR A 240 8.997 9.367 7.097 1.00 20.96 C
ATOM 3383 CE1 TYR A 240 8.113 8.325 7.179 1.00 22.25 C
ATOM 3385 CZ TYR A 240 8.150 7.317 6.171 1.00 27.67 C
ATOM 3386 OH TYR A 240 7.269 6.247 6.207 1.00 28.63 O
ATOM 3388 CE2 TYR A 240 9.034 7.397 5.159 1.00 25.36 C
ATOM 3390 CD2 TYR A 240 9.884 8.442 5.084 1.00 24.19 C
ATOM 3392 C TYR A 240 9.453 11.746 4.253 1.00 19.14 C
ATOM 3393 O TYR A 240 9.992 11.532 3.199 1.00 19.72 O
ATOM 3394 N THR A 241 8.172 11.873 4.401 1.00 21.32 N
ATOM 3396 CA THR A 241 7.309 11.777 3.214 1.00 24.31 C
ATOM 3398 CB THR A 241 6.015 11.129 3.549 1.00 24.08 C
ATOM 3400 OG1 THR A 241 5.443 11.711 4.720 1.00 25.38 O
ATOM 3402 CG2 THR A 241 6.238 9.670 3.924 1.00 28.14 C
ATOM 3406 C THR A 241 7.020 13.113 2.587 1.00 26.01 C
ATOM 3407 O THR A 241 6.175 13.200 1.682 1.00 27.85 O
ATOM 3408 N GLY A 242 7.684 14.159 3.041 1.00 26.13 N
ATOM 3410 CA GLY A 242 7.445 15.480 2.484 1.00 26.65 C
ATOM 3413 C GLY A 242 6.544 16.381 3.303 1.00 25.41 C
ATOM 3414 O GLY A 242 6.524 17.583 3.068 1.00 29.27 O
ATOM 3415 N GLY A 243 5.786 15.891 4.246 1.00 23.67 N
ATOM 3417 CA GLY A 243 5.002 16.882 4.959 1.00 23.78 C
ATOM 3420 C GLY A 243 5.719 17.300 6.239 1.00 21.57 C
ATOM 3421 O GLY A 243 6.944 17.532 6.218 1.00 20.45 O
ATOM 3422 N TYR A 244 4.939 17.380 7.296 1.00 22.18 N
ATOM 3424 CA TYR A 244 5.404 17.745 8.651 1.00 21.26 C
ATOM 3426 CB TYR A 244 4.991 19.201 8.963 1.00 20.92 C
ATOM 3429 CG TYR A 244 5.467 20.078 7.877 1.00 20.48 C
ATOM 3430 CD1 TYR A 244 4.696 20.312 6.749 1.00 20.98 C
ATOM 3432 CE1 TYR A 244 5.167 21.082 5.733 1.00 21.20 C
ATOM 3434 CZ TYR A 244 6.396 21.604 5.785 1.00 20.81 C
ATOM 3435 OH TYR A 244 6.852 22.332 4.745 1.00 23.64 O
ATOM 3437 CE2 TYR A 244 7.201 21.392 6.929 1.00 17.10 C
ATOM 3439 CD2 TYR A 244 6.714 20.660 7.920 1.00 14.54 C
ATOM 3441 C TYR A 244 4.789 16.816 9.621 1.00 21.28 C
ATOM 3442 O TYR A 244 3.778 16.224 9.353 1.00 23.43 O
ATOM 3443 N ASN A 245 5.381 16.692 10.800 1.00 19.64 N
ATOM 3445 CA ASN A 245 4.866 15.855 11.825 1.00 18.70 C
ATOM 3447 CB ASN A 245 5.322 14.418 11.590 1.00 18.51 C
ATOM 3450 CG ASN A 245 4.644 13.438 12.450 1.00 18.67 C
ATOM 3451 OD1 ASN A 245 3.509 13.611 12.925 1.00 21.26 O
ATOM 3452 ND2 ASN A 245 5.350 12.323 12.689 1.00 22.00 N
ATOM 3455 C ASN A 245 5.304 16.401 13.154 1.00 16.91 C
ATOM 3456 O ASN A 245 6.289 17.194 13.212 1.00 17.80 O
ATOM 3457 N THR A 246 4.533 16.035 14.141 1.00 17.22 N
ATOM 3459 CA THR A 246 4.696 16.445 15.504 1.00 17.23 C
ATOM 3461 CB THR A 246 3.454 17.242 15.971 1.00 17.67 C
ATOM 3463 OG1 THR A 246 3.368 18.458 15.223 1.00 18.24 O
ATOM 3465 CG2 THR A 246 3.534 17.710 17.400 1.00 20.37 C
ATOM 3469 C THR A 246 4.993 15.244 16.374 1.00 17.33 C
ATOM 3470 O THR A 246 4.123 14.398 16.664 1.00 16.60 O
ATOM 3471 N ILE A 247 6.221 15.237 16.902 1.00 16.92 N
ATOM 3473 CA ILE A 247 6.655 14.201 17.813 1.00 16.77 C
ATOM 3475 CB ILE A 247 7.536 13.106 17.091 1.00 16.85 C
ATOM 3477 CG1 ILE A 247 8.722 13.699 16.372 1.00 16.22 C
ATOM 3480 CD1 ILE A 247 9.721 12.674 15.892 1.00 14.19 C
ATOM 3484 CG2 ILE A 247 6.620 12.272 16.155 1.00 18.78 C
ATOM 3488 C ILE A 247 7.394 14.839 19.045 1.00 14.93 C
ATOM 3489 O ILE A 247 7.628 16.050 19.098 1.00 15.83 O
ATOM 3490 N SER A 248 7.659 14.020 20.030 1.00 14.46 N
ATOM 3492 CA SER A 248 8.268 14.443 21.285 1.00 14.38 C
ATOM 3494 CB SER A 248 7.262 14.230 22.426 1.00 14.68 C
ATOM 3497 OG SER A 248 6.080 14.988 22.271 1.00 16.96 O
ATOM 3499 C SER A 248 9.470 13.594 21.672 1.00 13.40 C
ATOM 3500 O SER A 248 9.626 12.448 21.227 1.00 12.06 O
ATOM 3501 N GLY A 249 10.306 14.151 22.557 1.00 11.90 N
ATOM 3503 CA GLY A 249 11.402 13.420 23.140 1.00 12.25 C
ATOM 3506 C GLY A 249 12.615 14.294 23.393 1.00 11.45 C
ATOM 3507 O GLY A 249 12.672 15.399 22.898 1.00 12.12 O
ATOM 3508 N THR A 250 13.607 13.759 24.103 1.00 10.99 N
ATOM 3510 CA THR A 250 14.898 14.476 24.200 1.00 9.84 C
ATOM 3512 CB THR A 250 15.835 13.937 25.257 1.00 9.57 C
ATOM 3514 OG1 THR A 250 15.885 12.543 25.195 1.00 10.83 O
ATOM 3516 CG2 THR A 250 15.260 14.258 26.612 1.00 11.12 C
ATOM 3520 C THR A 250 15.506 14.531 22.800 1.00 9.75 C
ATOM 3521 O THR A 250 16.312 15.393 22.517 1.00 11.31 O
ATOM 3522 N SER A 251 15.101 13.616 21.938 1.00 9.71 N
ATOM 3524 CA SER A 251 15.396 13.711 20.513 1.00 10.29 C
ATOM 3526 CB SER A 251 14.647 12.660 19.691 1.00 10.44 C
ATOM 3529 OG SER A 251 15.278 11.374 19.720 1.00 11.64 O
ATOM 3531 C SER A 251 15.132 15.058 19.850 1.00 10.60 C
ATOM 3532 O SER A 251 15.871 15.475 18.968 1.00 12.05 O
ATOM 3533 N MET A 252 14.023 15.698 20.246 1.00 11.35 N
ATOM 3535 CA MET A 252 13.598 16.937 19.649 1.00 12.05 C
ATOM 3537 CB MET A 252 12.081 17.000 19.803 1.00 10.74 C
ATOM 3540 CG MET A 252 11.275 16.163 18.811 1.00 16.05 C
ATOM 3543 SD MET A 252 11.445 14.393 18.855 1.00 12.67 S
ATOM 3544 CE MET A 252 12.360 14.105 17.508 1.00 14.70 C
ATOM 3548 C MET A 252 14.248 18.146 20.363 1.00 11.00 C
ATOM 3549 O MET A 252 14.372 19.200 19.805 1.00 10.97 O
ATOM 3550 N ALA A 253 14.615 17.978 21.628 1.00 11.44 N
ATOM 3552 CA ALA A 253 15.300 19.023 22.361 1.00 9.30 C
ATOM 3554 CB ALA A 253 l5.282 18.677 23.852 1.00 8.63 C
ATOM 3558 C ALA A 253 16.733 19.234 21.842 1.00 9.29 C
ATOM 3559 O ALA A 253 17.173 20.367 21.599 1.00 10.72 O
ATOM 3560 N THR A 254 17.388 18.107 21.578 1.00 9.20 N
ATOM 3562 CA THR A 254 18.776 18.047 21.127 1.00 9.63 C
ATOM 3564 CB THR A 254 19.131 16.592 20.838 1.00 11.67 C
ATOM 3566 OG1 THR A 254 19.001 15.823 22.036 1.00 9.34 O
ATOM 3568 CG2 THR A 254 20.504 16.467 20.434 1.00 9.85 C
ATOM 3572 C THR A 254 19.041 18.957 19.927 1.00 9.01 C
ATOM 3573 O THR A 254 19.932 19.782 19.958 1.00 9.02 O
ATOM 3574 N PRO A 255 18.255 18.848 18.856 1.00 10.43 N
ATOM 3575 CA PRO A 255 18.491 19.725 17.711 1.00 9.72 C
ATOM 3577 CB PRO A 255 17.607 19.149 16.621 1.00 11.04 C
ATOM 3580 CG PRO A 255 16.511 18.430 17.368 1.00 11.23 C
ATOM 3583 CD PRO A 255 17.253 17.817 18.535 1.00 11.38 C
ATOM 3586 C PRO A 255 18.195 21.185 17.941 1.00 10.12 C
ATOM 3587 O PRO A 255 18.724 22.018 17.171 1.00 9.83 O
ATOM 3588 N HIS A 256 17.398 21.535 18.943 1.00 10.53 N
ATOM 3590 CA HIS A 256 17.233 22.947 19.219 1.00 10.79 C
ATOM 3592 CB HIS A 256 16.192 23.258 20.298 1.00 11.66 C
ATOM 3595 CG HIS A 256 14.748 23.136 19.820 1.00 12.48 C
ATOM 3596 ND1 HIS A 256 14.086 21.930 19.732 1.00 11.32 N
ATOM 3598 CE1 HIS A 256 12.849 22.144 19.296 1.00 14.50 C
ATOM 3600 NE2 HIS A 256 12.709 23.434 19.040 1.00 12.79 N
ATOM 3602 CD2 HIS A 256 13.889 24.074 19.348 1.00 12.20 C
ATOM 3604 C HIS A 256 18.572 23.451 19.658 1.00 11.12 C
ATOM 3605 O HIS A 256 18.977 24.554 19.302 1.00 12.50 O
ATOM 3606 N VAL A 257 19.264 22.660 20.474 1.00 10.13 N
ATOM 3608 CA VAL A 257 20.558 23.078 20.969 1.00 9.71 C
ATOM 3610 CB VAL A 257 20.966 22.264 22.219 1.00 10.12 C
ATOM 3612 CG1 VAL A 257 22.407 22.589 22.653 1.00 10.84 C
ATOM 3616 CG2 VAL A 257 19.951 22.451 23.324 1.00 11.41 C
ATOM 3620 C VAL A 257 21.632 22.993 19.871 1.00 10.99 C
ATOM 3621 O VAL A 257 22.483 23.871 19.782 1.00 11.55 O
ATOM 3622 N ALA A 258 21.664 21.933 19.070 1.00 10.95 N
ATOM 3624 CA ALA A 258 22.625 21.857 17.985 1.00 10.24 C
ATOM 3626 CB ALA A 258 22.459 20.568 17.233 1.00 9.96 C
ATOM 3630 C ALA A 258 22.446 23.027 17.061 1.00 11.33 C
ATOM 3631 O ALA A 258 23.426 23.621 16.598 1.00 10.81 O
ATOM 3632 N GLY A 259 21.191 23.351 16.799 1.00 11.66 N
ATOM 3634 CA GLY A 259 20.929 24.467 15.916 1.00 12.69 C
ATOM 3637 C GLY A 259 21.378 25.792 16.529 1.00 11.32 C
ATOM 3638 O GLY A 259 21.928 26.653 15.830 1.00 12.25 O
ATOM 3639 N LEU A 260 21.044 25.991 17.781 1.00 10.90 N
ATOM 3641 CA LEU A 260 21.453 27.191 18.479 1.00 11.40 C
ATOM 3643 CB LEU A 260 20.945 27.240 19.877 1.00 10.96 C
ATOM 3646 CG LEU A 260 21.372 28.483 20.678 1.00 11.84 C
ATOM 3648 CD1 LEU A 260 20.781 29.683 20.099 1.00 16.22 C
ATOM 3652 CD2 LEU A 260 20.948 28.349 22.174 1.00 12.84 C
ATOM 3656 C LEU A 260 22.984 27.291 18.477 1.00 12.53 C
ATOM 3657 O LEU A 260 23.558 28.384 18.205 1.00 11.28 O
ATOM 3658 N ALA A 261 23.644 26.153 18.745 1.00 11.39 N
ATOM 3660 CA ALA A 261 25.093 26.133 18.661 1.00 11.97 C
ATOM 3662 CB ALA A 261 25.604 24.716 18.889 1.00 13.65 C
ATOM 3666 C ALA A 261 25.607 26.638 17.292 1.00 12.95 C
ATOM 3667 O ALA A 261 26.563 27.413 17.203 1.00 12.12 O
ATOM 3668 N ALA A 262 24.998 26.144 16.229 1.00 11.02 N
ATOM 3670 CA ALA A 262 25.435 26.520 14.869 1.00 12.24 C
ATOM 3672 CB ALA A 262 24.731 25.669 13.828 1.00 12.25 C
ATOM 3676 C ALA A 262 25.200 28.002 14.619 1.00 13.52 C
ATOM 3677 O ALA A 262 26.045 28.684 13.996 1.00 13.55 O
ATOM 3678 N LYS A 263 24.091 28.505 15.135 1.00 13.42 N
ATOM 3680 CA LYS A 263 23.730 29.913 15.021 1.00 13.54 C
ATOM 3682 CB LYS A 263 22.319 30.164 15.511 1.00 14.20 C
ATOM 3685 CG LYS A 263 21.797 31.603 15.356 1.00 13.78 C
ATOM 3688 CD LYS A 263 20.412 31.725 15.984 1.00 15.37 C
ATOM 3691 CE LYS A 263 19.936 33.158 16.011 1.00 17.70 C
ATOM 3694 NZ LYS A 263 19.671 33.740 14.618 1.00 14.92 N
ATOM 3698 C LYS A 263 24.754 30.774 15.736 1.00 12.81 C
ATOM 3699 O LYS A 263 25.225 31.781 15.148 1.00 13.25 O
ATOM 3700 N ILE A 264 25.133 30.393 16.961 1.00 12.96 N
ATOM 3702 CA ILE A 264 26.107 31.136 17.723 1.00 12.47 C
ATOM 3704 CB ILE A 264 26.209 30.579 19.150 1.00 12.83 C
ATOM 3706 CG1 ILE A 264 24.895 30.799 19.927 1.00 12.96 C
ATOM 3709 CD1 ILE A 264 24.829 30.017 21.259 1.00 13.94 C
ATOM 3713 CG2 ILE A 264 27.382 31.146 19.925 1.00 12.54 C
ATOM 3717 C ILE A 264 27.478 31.081 17.018 1.00 12.78 C
ATOM 3718 O ILE A 264 28.147 32.110 16.835 1.00 12.72 O
ATOM 3719 N TRP A 265 27.843 29.890 16.527 1.00 12.74 N
ATOM 3721 CA TRP A 265 29.194 29.711 15.984 1.00 13.37 C
ATOM 3723 CB TRP A 265 29.445 28.252 15.665 1.00 13.60 C
ATOM 3726 CG TRP A 265 30.859 27.836 15.758 1.00 12.37 C
ATOM 3727 CD1 TRP A 265 31.987 28.624 15.964 1.00 12.89 C
ATOM 3729 NE1 TRP A 265 33.101 27.823 16.063 1.00 14.49 N
ATOM 3731 CE2 TRP A 265 32.705 26.514 15.998 1.00 16.16 C
ATOM 3732 CD2 TRP A 265 31.313 26.493 15.796 1.00 12.95 C
ATOM 3733 CE3 TRP A 265 30.679 25.254 15.657 1.00 14.36 C
ATOM 3735 CZ3 TRP A 265 31.472 24.110 15.707 1.00 12.68 C
ATOM 3737 CH2 TRP A 265 32.809 24.180 15.941 1.00 12.39 C
ATOM 3739 CZ2 TRP A 265 33.462 25.359 16.069 1.00 15.97 C
ATOM 3741 C TRP A 265 29.378 30.560 14.732 1.00 13.71 C
ATOM 3742 O TRP A 265 30.423 31.117 14.530 1.00 17.12 O
ATOM 3743 N SER A 266 28.330 30.599 13.922 1.00 15.25 N
ATOM 3745 CA SER A 266 28.307 31.345 12.676 1.00 14.75 C
ATOM 3747 CB SER A 266 27.000 31.130 11.945 1.00 15.47 C
ATOM 3750 OG SER A 266 26.987 31.917 10.741 1.00 18.19 O
ATOM 3752 C SER A 266 28.498 32.835 12.962 1.00 16.77 C
ATOM 3753 O SER A 266 29.218 33.537 12.227 1.00 16.07 O
ATOM 3754 N ALA A 267 27.903 33.307 14.053 1.00 15.63 N
ATOM 3756 CA ALA A 267 28.046 34.711 14.450 1.00 17.65 C
ATOM 3758 CB ALA A 267 26.911 35.093 15.318 1.00 19.01 C
ATOM 3762 C ALA A 267 29.405 35.056 15.092 1.00 19.17 C
ATOM 3763 O ALA A 267 29.744 36.249 15.277 1.00 18.66 O
ATOM 3764 N ASN A 268 30.188 34.053 15.465 1.00 17.88 N
ATOM 3766 CA ASN A 268 31.557 34.318 15.886 1.00 20.05 C
ATOM 3768 CB ASN A 268 31.688 34.603 17.324 1.00 20.47 C
ATOM 3771 CG ASN A 268 33.120 35.029 17.701 1.00 23.58 C
ATOM 3772 OD1 ASN A 268 34.017 35.076 16.860 1.00 24.59 O
ATOM 3773 ND2 ASN A 268 33.327 35.286 18.961 1.00 27.93 N
ATOM 3776 C ASN A 268 32.437 33.156 15.520 1.00 18.98 C
ATOM 3777 O ASN A 268 32.651 32.264 16.321 1.00 17.09 O
ATOM 3778 N THR A 269 32.915 33.169 14.289 1.00 19.21 N
ATOM 3780 CA THR A 269 33.696 32.076 13.772 1.00 19.25 C
ATOM 3782 CB THR A 269 33.838 32.153 12.207 1.00 21.27 C
ATOM 3784 OG1 THR A 269 34.379 33.443 11.889 1.00 21.88 O
ATOM 3786 CG2 THR A 269 32.479 32.127 11.565 1.00 23.50 C
ATOM 3790 C THR A 269 35.055 32.025 14.380 1.00 19.11 C
ATOM 3791 O THR A 269 35.761 31.117 14.072 1.00 19.77 O
ATOM 3792 N SER A 270 35.435 32.929 15.297 1.00 19.17 N
ATOM 3794 CA SER A 270 36.732 32.774 15.936 1.00 19.54 C
ATOM 3796 CB ASER A 270 37.231 34.105 16.454 0.50 19.48 C
ATOM 3797 CB BSER A 270 37.264 34.116 16.400 0.50 19.66 C
ATOM 3802 OG ASER A 270 36.235 34.749 17.225 0.50 21.34 O
ATOM 3803 OG BSER A 270 37.628 34.922 15.280 0.50 22.88 O
ATOM 3806 C SER A 270 36.679 31.795 17.100 1.00 17.42 C
ATOM 3807 O SER A 270 37.688 31.382 17.637 1.00 19.69 O
ATOM 3808 N LEU A 271 35.493 31.392 17.484 1.00 15.84 N
ATOM 3810 CA LEU A 271 35.364 30.456 18.595 1.00 13.46 C
ATOM 3812 CB LEU A 271 33.910 30.345 19.026 1.00 14.65 C
ATOM 3815 CG LEU A 271 33.146 31.575 19.466 1.00 15.68 C
ATOM 3817 CD1 LEU A 271 31.659 31.196 19.782 1.00 18.69 C
ATOM 3821 CD2 LEU A 271 33.807 32.216 20.685 1.00 21.20 C
ATOM 3825 C LEU A 271 35.806 29.028 18.220 1.00 12.04 C
ATOM 3826 O LEU A 271 35.573 28.546 17.091 1.00 11.86 O
ATOM 3827 N SER A 272 36.323 28.335 19.220 1.00 12.57 N
ATOM 3829 CA SER A 272 36.545 26.919 19.145 1.00 11.98 C
ATOM 3831 CB SER A 272 37.710 26.489 20.040 1.00 12.49 C
ATOM 3834 OG SER A 272 37.433 26.778 21.421 1.00 12.53 O
ATOM 3836 C SER A 272 35.275 26.244 19.663 1.00 11.47 C
ATOM 3837 O SER A 272 34.372 26.889 20.269 1.00 9.92 O
ATOM 3838 N HIS A 273 35.225 24.937 19.454 1.00 11.48 N
ATOM 3840 CA HIS A 273 34.074 24.187 19.920 1.00 11.75 C
ATOM 3842 CB HIS A 273 34.187 22.750 19.445 1.00 13.59 C
ATOM 3845 CG HIS A 273 35.160 21.921 20.197 1.00 13.01 C
ATOM 3846 ND1 HIS A 273 36.456 22.312 20.379 1.00 11.73 N
ATOM 3848 CE1 HIS A 273 37.072 21.402 21.124 1.00 13.52 C
ATOM 3850 NE2 HIS A 273 36.243 20.394 21.343 1.00 12.58 N
ATOM 3852 CD2 HIS A 273 35.039 20.708 20.787 1.00 14.38 C
ATOM 3854 C HIS A 273 33.887 24.268 21.427 1.00 11.79 C
ATOM 3855 O HIS A 273 32.723 24.252 21.930 1.00 10.83 O
ATOM 3856 N SER A 274 34.975 24.276 22.191 1.00 10.50 N
ATOM 3858 CA SER A 274 34.813 24.319 23.643 1.00 10.49 C
ATOM 3860 CB SER A 274 36.035 23.803 24.397 1.00 13.18 C
ATOM 3863 OG SER A 274 37.161 24.639 24.166 1.00 12.23 O
ATOM 3865 C SER A 274 34.478 25.702 24.113 1.00 12.50 C
ATOM 3866 O SER A 274 33.783 25.849 25.123 1.00 11.08 O
ATOM 3867 N GLN A 275 34.919 26.739 23.418 1.00 11.42 N
ATOM 3869 CA GLN A 275 34.425 28.072 23.784 1.00 11.21 C
ATOM 3871 CB GLN A 275 35.132 29.188 22.999 1.00 11.23 C
ATOM 3874 CG GLN A 275 36.608 29.464 23.375 1.00 13.15 C
ATOM 3877 CD GLN A 275 37.192 30.473 22.413 1.00 13.10 C
ATOM 3878 OE1 GLN A 275 37.323 30.182 21.228 1.00 15.35 O
ATOM 3879 NE2 GLN A 275 37.555 31.677 22.923 1.00 11.91 N
ATOM 3882 C GLN A 275 32.898 28.177 23.457 1.00 11.10 C
ATOM 3883 O GLN A 275 32.150 28.776 24.217 1.00 10.23 O
ATOM 3884 N LEU A 276 32.492 27.556 22.340 1.00 10.08 N
ATOM 3886 CA LEU A 276 31.067 27.521 21.932 1.00 10.49 C
ATOM 3888 CB LEU A 276 30.909 26.866 20.582 1.00 10.65 C
ATOM 3891 CG LEU A 276 29.466 26.606 20.164 1.00 8.36 C
ATOM 3893 CD1 LEU A 276 28.715 27.856 20.038 1.00 9.01 C
ATOM 3897 CD2 LEU A 276 29.489 25.869 18.849 1.00 11.63 C
ATOM 3901 C LEU A 276 30.272 26.790 23.041 1.00 11.06 C
ATOM 3902 O LEU A 276 29.226 27.252 23.494 1.00 10.87 O
ATOM 3903 N ARG A 277 30.783 25.671 23.524 1.00 9.13 N
ATOM 3905 CA ARG A 277 30.104 24.934 24.560 1.00 11.95 C
ATOM 3907 CB ARG A 277 30.915 23.671 24.913 1.00 10.95 C
ATOM 3910 CG ARG A 277 30.335 22.793 26.018 1.00 13.22 C
ATOM 3913 CD ARG A 277 31.103 21.490 26.229 1.00 13.28 C
ATOM 3916 NE ARG A 277 30.415 20.601 27.149 1.00 13.25 N
ATOM 3918 CZ ARG A 277 30.892 19.416 27.518 1.00 14.34 C
ATOM 3919 NH1 ARG A 277 32.089 19.014 27.110 1.00 14.38 N
ATOM 3922 NH2 ARG A 277 30.190 18.660 28.345 1.00 13.28 N
ATOM 3925 C ARG A 277 29.974 25.722 25.858 1.00 12.12 C
ATOM 3926 O ARG A 277 28.949 25.722 26.538 1.00 12.16 O
ATOM 3927 N THR A 278 31.023 26.469 26.175 1.00 12.13 N
ATOM 3929 CA THR A 278 31.049 27.295 27.359 1.00 11.62 C
ATOM 3931 CB THR A 278 32.461 27.918 27.485 1.00 12.51 C
ATOM 3933 OG1 THR A 278 33.379 26.892 27.846 1.00 15.78 O
ATOM 3935 CG2 THR A 278 32.551 28.829 28.624 1.00 17.34 C
ATOM 3939 C THR A 278 29.990 28.388 27.287 1.00 10.34 C
ATOM 3940 O THR A 278 29.372 28.715 28.294 1.00 11.22 O
ATOM 3941 N GLU A 279 297.75 28.943 26.101 1.00 10.24 N
ATOM 3943 CA GLU A 279 28.804 30.034 25.920 1.00 10.36 C
ATOM 3945 CB GLU A 279 29.090 30.744 24.607 1.00 13.04 C
ATOM 3948 CG GLU A 279 28.155 31.799 24.172 1.00 13.67 C
ATOM 3951 CD GLU A 279 27.827 32.923 25.148 1.00 11.41 C
ATOM 3952 OE1 GLU A 279 28.413 33.084 26.245 1.00 12.14 O
ATOM 3953 OE2 GLU A 279 26.928 33.691 24.766 1.00 13.94 O
ATOM 3954 C GLU A 279 27.387 29.439 25.978 1.00 10.50 C
ATOM 3955 O GLU A 279 26.477 30.093 26.462 1.00 10.16 O
ATOM 3956 N LEU A 280 27.198 28.205 25.499 1.00 10.73 N
ATOM 3958 CA LEU A 280 25.898 27.507 25.652 1.00 10.31 C
ATOM 3960 CB LEU A 280 25.846 26.124 24.973 1.00 12.52 C
ATOM 3963 CG LEU A 280 25.772 26.107 23.451 1.00 13.85 C
ATOM 3965 CD1 LEU A 280 25.964 24.631 22.911 1.00 17.63 C
ATOM 3969 CD2 LEU A 280 24.435 26.669 22.957 1.00 15.10 C
ATOM 3973 C LEU A 280 25.613 27.411 27.150 1.00 10.89 C
ATOM 3974 O LEU A 280 24.492 27.626 27.606 1.00 12.00 O
ATOM 3975 N GLN A 281 26.630 27.040 27.907 1.00 9.57 N
ATOM 3977 CA GLN A 281 26.479 26.931 29.322 1.00 11.52 C
ATOM 3979 CB GLN A 281 27.755 26.360 29.925 1.00 11.03 C
ATOM 3982 CG GLN A 281 28.028 24.891 29.487 1.00 12.22 C
ATOM 3985 CD GLN A 281 29.376 24.377 29.981 1.00 14.98 C
ATOM 3986 OE1 GLN A 281 30.115 25.172 30.555 1.00 15.61 O
ATOM 3987 NE2 GLN A 281 29.731 23.103 29.697 1.00 9.95 N
ATOM 3990 C GLN A 281 26.161 28.313 29.924 1.00 10.71 C
ATOM 3991 O GLN A 281 25.309 28.409 30.815 1.00 11.77 O
ATOM 3992 N ASN A 282 26.883 29.367 29.484 1.00 10.78 N
ATOM 3994 CA ASN A 282 26.722 30.715 30.090 1.00 10.24 C
ATOM 3996 CB ASN A 282 27.683 31.745 29.504 1.00 10.08 C
ATOM 3999 CG ASN A 282 29.136 31.482 29.812 1.00 13.02 C
ATOM 4000 OD1 ASN A 282 29.471 30.830 30.809 1.00 14.49 O
ATOM 4001 ND2 ASN A 282 30.003 32.000 28.973 1.00 12.29 N
ATOM 4004 C ASN A 282 25.275 31.172 29.788 1.00 11.08 C
ATOM 4005 O ASN A 282 24.588 31.667 30.681 1.00 12.10 O
ATOM 4006 N ARG A 283 24.829 30.902 28.575 1.00 9.30 N
ATOM 4008 CA ARG A 283 23.484 31.298 28.160 1.00 10.89 C
ATOM 4010 CB ARG A 283 23.305 31.055 26.697 1.00 10.96 C
ATOM 4013 CG ARG A 283 23.894 32.191 25.842 1.00 13.15 C
ATOM 4016 CD ARG A 283 23.768 31.880 24.383 1.00 11.91 C
ATOM 4019 NE ARG A 283 24.469 32.831 23.466 1.00 12.89 N
ATOM 4021 CZ ARG A 283 23.985 33.290 22.311 1.00 15.41 C
ATOM 4022 NH1 ARG A 283 22.780 33.006 21.903 1.00 15.22 N
ATOM 4025 NH2 ARG A 283 24.722 34.053 21.528 1.00 14.46 N
ATOM 4028 C ARG A 283 22.450 30.528 28.963 1.00 10.28 C
ATOM 4029 O ARG A 283 21.390 31.063 29.298 1.00 11.49 O
ATOM 4030 N ALA A 284 22.741 29.263 29.220 1.00 10.27 N
ATOM 4032 CA ALA A 284 21.789 28.438 29.957 1.00 10.07 C
ATOM 4034 CB ALA A 284 22.358 27.011 30.158 1.00 11.06 C
ATOM 4038 C ALA A 284 21.493 29.093 31.306 1.00 10.53 C
ATOM 4039 O ALA A 284 20.349 29.096 31.809 1.00 11.23 O
ATOM 4040 N LYS A 285 22.539 29.620 31.899 1.00 10.42 N
ATOM 4042 CA LYS A 285 22.446 30.158 33.238 1.00 10.99 C
ATOM 4044 CB LYS A 285 23.846 30.372 33.821 1.00 11.62 C
ATOM 4047 CG LYS A 285 24.664 29.120 34.054 1.00 12.18 C
ATOM 4050 CD LYS A 285 26.057 29.529 34.477 1.00 16.21 C
ATOM 4053 CE LYS A 285 27.062 28.492 34.451 1.00 15.01 C
ATOM 4056 NZ LYS A 285 28.349 29.067 35.077 1.00 17.35 N
ATOM 4060 C LYS A 285 21.566 31.386 33.281 1.00 11.59 C
ATOM 4061 O LYS A 285 21.120 31.753 34.363 1.00 12.70 O
ATOM 4062 N VAL A 286 21.419 32.094 32.168 1.00 10.88 N
ATOM 4064 CA VAL A 286 20.604 33.255 32.110 1.00 12.69 C
ATOM 4066 CB VAL A 286 20.719 33.961 30.788 1.00 12.21 C
ATOM 4068 CG1 VAL A 286 19.838 35.220 30.746 1.00 15.12 C
ATOM 4072 CG2 VAL A 286 22.221 34.402 30.612 1.00 13.05 C
ATOM 4076 C VAL A 286 19.153 32.850 32.362 1.00 13.03 C
ATOM 4077 O VAL A 286 18.399 33.651 32.960 1.00 13.04 O
ATOM 4078 N TYR A 287 18.788 31.649 31.885 1.00 11.44 N
ATOM 4080 CA TYR A 287 17.427 31.124 32.057 1.00 12.02 C
ATOM 4082 CB TYR A 287 16.740 30.949 30.718 1.00 12.84 C
ATOM 4085 CG TYR A 287 16.587 32.235 29.976 1.00 12.74 C
ATOM 4086 CD1 TYR A 287 15.615 33.157 30.344 1.00 14.60 C
ATOM 4088 CE1 TYR A 287 15.490 34.343 29.748 1.00 14.77 C
ATOM 4090 CZ TYR A 287 16.343 34.709 28.753 1.00 15.62 C
ATOM 4091 OH TYR A 287 16.139 35.938 28.183 1.00 18.73 O
ATOM 4093 CE2 TYR A 287 17.372 33.852 28.377 1.00 13.12 C
ATOM 4095 CD2 TYR A 287 17.521 32.646 28.995 1.00 11.74 C
ATOM 4097 C TYR A 287 17.427 29.860 32.905 1.00 12.13 C
ATOM 4098 O TYR A 287 17.303 28.740 32.452 1.00 13.99 O
ATOM 4099 N ASP A 288 17.631 30.057 34.208 1.00 12.75 N
ATOM 4101 CA ASP A 288 17.553 29.009 35.170 1.00 11.58 C
ATOM 4103 CB ASP A 288 17.721 29.636 36.551 1.00 11.65 C
ATOM 4106 CG ASP A 288 17.912 28.612 37.687 1.00 15.60 C
ATOM 4107 OD1 ASP A 288 18.065 27.373 37.473 1.00 17.35 O
ATOM 4108 OD2 ASP A 288 17.934 29.001 38.898 1.00 15.75 O
ATOM 4109 C ASP A 288 16.174 28.337 35.056 1.00 12.45 C
ATOM 4110 O ASP A 288 15.186 29.032 34.950 1.00 13.43 O
ATOM 4111 N ILE A 289 16.112 27.026 34.986 1.00 10.72 N
ATOM 4113 CA ILE A 289 14.812 26.271 34.969 1.00 12.80 C
ATOM 4115 CB ILE A 289 14.860 25.168 33.912 1.00 12.78 C
ATOM 4117 CG1 ILE A 289 15.042 25.785 32.535 1.00 13.67 C
ATOM 4120 CD1 ILE A 289 13.745 26.474 31.867 1.00 13.36 C
ATOM 4124 CG2 ILE A 289 13.659 24.220 33.989 1.00 14.37 C
ATOM 4128 C ILE A 289 14.517 25.742 36.352 1.00 13.79 C
ATOM 4129 O ILE A 289 15.376 25.140 37.045 1.00 12.95 O
ATOM 4130 N LYS A 290 13.299 26.006 36.825 1.00 14.91 N
ATOM 4132 CA LYS A 290 12.904 25.675 38.185 1.00 16.59 C
ATOM 4134 CB LYS A 290 12.600 26.955 38.930 1.00 17.67 C
ATOM 4137 CG LYS A 290 13.878 27.786 39.143 1.00 21.86 C
ATOM 4140 CD LYS A 290 13.627 28.893 40.134 1.00 28.07 C
ATOM 4143 CE LYS A 290 13.554 30.215 39.470 1.00 34.10 C
ATOM 4146 NZ LYS A 290 13.272 31.317 40.512 1.00 39.60 N
ATOM 4150 C LYS A 290 11.648 24.807 38.235 1.00 16.71 C
ATOM 4151 O LYS A 290 11.200 24.444 39.330 1.00 18.64 O
ATOM 4152 N GLY A 291 11.119 24.507 37.071 1.00 15.39 N
ATOM 4154 CA GLY A 291 9.895 23.740 36.907 1.00 14.24 C
ATOM 4157 C GLY A 291 10.134 22.294 36.570 1.00 14.85 C
ATOM 4158 O GLY A 291 10.997 21.990 35.707 1.00 15.05 O
ATOM 4159 N GLY A 292 9.376 21.387 37.185 1.00 15.54 N
ATOM 4161 CA GLY A 292 9.524 19.984 36.896 1.00 14.12 C
ATOM 4164 C GLY A 292 10.116 19.187 38.030 1.00 15.07 C
ATOM 4165 O GLY A 292 10.717 19.734 38.959 1.00 15.42 O
ATOM 4166 N ILE A 293 9.932 17.878 37.980 1.00 14.74 N
ATOM 4168 CA ILE A 293 10.363 17.018 39.044 1.00 15.41 C
ATOM 4170 CB ILE A 293 9.881 15.599 38.776 1.00 15.32 C
ATOM 4172 CG1 ILE A 293 8.342 15.549 38.894 1.00 18.82 C
ATOM 4175 CD1 ILE A 293 7.731 14.260 38.471 1.00 21.20 C
ATOM 4179 CG2 ILE A 293 10.526 14.610 39.740 1.00 15.00 C
ATOM 4183 C ILE A 293 11.885 17.052 39.176 1.00 16.26 C
ATOM 4184 O ILE A 293 12.586 16.688 38.214 1.00 14.62 O
ATOM 4185 N GLY A 294 12.367 17.439 40.346 1.00 14.72 N
ATOM 4187 CA GLY A 294 13.810 17.581 40.559 1.00 15.36 C
ATOM 4190 C GLY A 294 14.449 18.897 40.107 1.00 13.63 C
ATOM 4191 O GLY A 294 15.660 19.095 40.315 1.00 15.06 O
ATOM 4192 N ALA A 295 13.688 19.803 39.516 1.00 14.00 N
ATOM 4194 CA ALA A 295 14.220 21.064 39.058 1.00 13.92 C
ATOM 4196 CB ALA A 295 13.381 21.661 37.869 1.00 14.66 C
ATOM 4200 C ALA A 295 14.226 21.990 40.236 1.00 16.73 C
ATOM 4201 O ALA A 295 13.451 21.811 41.178 1.00 16.12 O
ATOM 4202 N GLY A 296 15.094 22.986 40.227 1.00 16.79 N
ATOM 4204 CA GLY A 296 15.114 23.941 41.340 1.00 18.72 C
ATOM 4207 C GLY A 296 16.052 25.058 41.052 1.00 17.66 C
ATOM 4208 O GLY A 296 16.601 25.160 39.963 1.00 16.21 O
ATOM 4209 N THR A 297 16.240 25.979 41.992 1.00 17.88 N
ATOM 4211 CA THR A 297 17.144 27.068 41.712 1.00 17.28 C
ATOM 4213 CB THR A 297 17.117 27.981 42.941 1.00 19.91 C
ATOM 4215 OG1 THR A 297 15.763 28.455 43.102 1.00 19.89 O
ATOM 4217 CG2 THR A 297 17.981 29.177 42.689 1.00 19.92 C
ATOM 4221 C THR A 297 18.563 26.600 41.472 1.00 17.13 C
ATOM 4222 O THR A 297 19.104 25.832 42.248 1.00 18.37 O
ATOM 4223 N GLY A 298 19.193 27.074 40.410 1.00 14.91 N
ATOM 4225 CA GLY A 298 20.569 26.702 40.153 1.00 15.10 C
ATOM 4228 C GLY A 298 20.684 25.492 39.273 1.00 14.01 C
ATOM 4229 O GLY A 298 19.717 25.039 38.656 1.00 12.62 O
ATOM 4230 N ASP A 299 21.882 24.932 39.243 1.00 13.64 N
ATOM 4232 CA ASP A 299 22.189 23.741 38.460 1.00 13.68 C
ATOM 4234 CB ASP A 299 23.689 23.623 38.447 1.00 14.28 C
ATOM 4237 CG ASP A 299 24.229 22.342 37.843 1.00 15.32 C
ATOM 4238 OD1 ASP A 299 23.578 21.787 36.970 1.00 13.87 O
ATOM 4239 OD2 ASP A 299 25.330 21.885 38.238 1.00 13.70 O
ATOM 4240 C ASP A 299 21.507 22.602 39.092 1.00 14.87 C
ATOM 4241 O ASP A 299 21.657 22.381 40.306 1.00 16.32 O
ATOM 4242 N ASP A 300 20.664 21.901 38.348 1.00 12.69 N
ATOM 4244 CA ASP A 300 19.921 20.812 38.953 1.00 12.30 C
ATOM 4246 CB ASP A 300 18.489 21.282 39.369 1.00 12.84 C
ATOM 4249 CG ASP A 300 17.615 21.597 38.192 1.00 11.72 C
ATOM 4250 OD1 ASP A 300 17.330 20.687 37.428 1.00 13.65 O
ATOM 4251 OD2 ASP A 300 17.079 22.691 38.018 1.00 14.33 O
ATOM 4252 C ASP A 300 19.928 19.603 38.011 1.00 13.91 C
ATOM 4253 O ASP A 300 20.278 19.699 36.822 1.00 13.63 O
ATOM 4254 N TYR A 301 19.514 18.462 38.539 1.00 13.49 N
ATOM 4256 CA TYR A 301 19.627 17.220 37.803 1.00 12.93 C
ATOM 4258 CB TYR A 301 19.868 16.046 38.777 1.00 11.22 C
ATOM 4261 CG TYR A 301 18.804 15.846 39.823 1.00 13.88 C
ATOM 4262 CD1 TYR A 301 17.648 15.225 39.523 1.00 14.91 C
ATOM 4264 CE1 TYR A 301 16.621 15.079 40.531 1.00 17.24 C
ATOM 4266 CZ TYR A 301 16.809 15.580 41.788 1.00 19.26 C
ATOM 4267 OH TYR A 301 15.803 15.394 42.776 1.00 20.79 O
ATOM 4269 CE2 TYR A 301 17.977 16.242 42.081 1.00 16.95 C
ATOM 4271 CD2 TYR A 301 18.948 16.384 41.095 1.00 13.89 C
ATOM 4273 C TYR A 301 18.421 16.951 36.875 1.00 11.64 C
ATOM 4274 O TYR A 301 18.419 15.954 36.154 1.00 11.11 O
ATOM 4275 N ALA A 302 17.435 17.846 36.832 1.00 11.29 N
ATOM 4277 CA ALA A 302 16.389 17.756 35.829 1.00 10.84 C
ATOM 4279 CB ALA A 302 15.006 18.227 36.391 1.00 12.99 C
ATOM 4283 C ALA A 302 16.684 18.574 34.581 1.00 10.79 C
ATOM 4284 O ALA A 302 16.424 18.146 33.444 1.00 11.72 O
ATOM 4285 N SER A 303 17.194 19.774 34.790 1.00 10.48 N
ATOM 4287 CA SER A 303 17.364 20.706 33.697 1.00 9.41 C
ATOM 4289 CB SER A 303 16.512 21.934 33.969 1.00 9.70 C
ATOM 4292 OG SER A 303 16.992 22.660 35.130 1.00 12.05 O
ATOM 4294 C SER A 303 18.819 21.172 33.468 1.00 10.16 C
ATOM 4295 O SER A 303 19.049 21.949 32.566 1.00 10.53 O
ATOM 4296 N GLY A 304 19.742 20.739 34.303 1.00 8.73 N
ATOM 4298 CA GLY A 304 21.132 21.139 34.201 1.00 10.18 C
ATOM 4301 C GLY A 304 21.273 22.616 34.479 1.00 10.17 C
ATOM 4302 O GLY A 304 20.710 23.138 35.422 1.00 10.02 O
ATOM 4303 N PHE A 305 22.102 23.286 33.664 1.00 11.73 N
ATOM 4305 CA PHE A 305 22.452 24.644 33.880 1.00 10.68 C
ATOM 4307 CB PHE A 305 23.661 25.048 33.036 1.00 10.84 C
ATOM 4310 CG PHE A 305 24.977 24.418 33.419 1.00 11.70 C
ATOM 4311 CD1 PHE A 305 25.070 23.280 34.195 1.00 12.20 C
ATOM 4313 CE1 PHE A 305 26.316 22.689 34.511 1.00 12.74 C
ATOM 4315 CZ PHE A 305 27.499 23.265 33.973 1.00 11.93 C
ATOM 4317 CE2 PHE A 305 27.380 24.372 33.184 1.00 11.62 C
ATOM 4319 CD2 PHE A 305 26.157 24.941 32.891 1.00 12.26 C
ATOM 4321 C PHE A 305 21.349 25.614 33.554 1.00 11.13 C
ATOM 4322 O PHE A 305 21.368 26.748 34.022 1.00 11.39 O
ATOM 4323 N GLY A 306 20.364 25.161 32.811 1.00 10.40 N
ATOM 4325 CA GLY A 306 19.276 26.018 32.414 1.00 10.88 C
ATOM 4328 C GLY A 306 18.926 25.834 30.963 1.00 11.20 C
ATOM 4329 O GLY A 306 19.208 24.812 30.318 1.00 9.40 O
ATOM 4330 N TYR A 307 18.291 26.863 30.443 1.00 10.29 N
ATOM 4332 CA TYR A 307 17.803 26.905 29.077 1.00 11.10 C
ATOM 4334 CB TYR A 307 16.311 27.194 29.162 1.00 10.85 C
ATOM 4337 CG TYR A 307 15.557 27.309 27.870 1.00 10.79 C
ATOM 4338 CD1 TYR A 307 16.087 26.885 26.660 1.00 10.35 C
ATOM 4340 CE1 TYR A 307 15.374 27.001 25.479 1.00 10.97 C
ATOM 4342 CZ TYR A 307 14.086 27.458 25.503 1.00 13.85 C
ATOM 4343 OH TYR A 307 13.388 27.607 24.308 1.00 13.18 O
ATOM 4345 CE2 TYR A 307 13.531 27.912 26.705 1.00 13.38 C
ATOM 4347 CD2 TYR A 307 14.260 27.849 27.860 1.00 11.68 C
ATOM 4349 C TYR A 307 18.479 27.939 28.217 1.00 12.67 C
ATOM 4350 O TYR A 307 18.140 29.113 28.271 1.00 13.67 O
ATOM 4351 N PRO A 308 19.440 27.555 27.389 1.00 11.31 N
ATOM 4352 CA PRO A 308 20.118 28.547 26.531 1.00 11.31 C
ATOM 4354 CB PRO A 308 21.315 27.780 25.971 1.00 10.82 C
ATOM 4357 CG PRO A 308 20.941 26.293 26.070 1.00 11.80 C
ATOM 4360 CD PRO A 308 19.833 26.179 27.077 1.00 12.92 C
ATOM 4363 C PRO A 308 19.245 29.003 25.361 1.00 11.34 C
ATOM 4364 O PRO A 308 18.604 28.159 24.689 1.00 10.74 O
ATOM 4365 N ARG A 309 19.314 30.266 25.051 1.00 12.86 N
ATOM 4367 CA ARG A 309 18.427 30.864 24.076 1.00 13.91 C
ATOM 4369 CB ARG A 309 17.252 31.527 24.844 1.00 13.02 C
ATOM 4372 CG ARG A 309 16.469 30.638 25.781 1.00 13.54 C
ATOM 4375 CD ARG A 309 15.375 31.251 26.661 1.00 14.50 C
ATOM 4378 NE ARG A 309 14.099 31.449 25.978 1.00 15.52 N
ATOM 4380 CZ ARG A 309 13.022 31.993 26.525 1.00 16.18 C
ATOM 4381 NH1 ARG A 309 13.055 32.423 27.777 1.00 12.53 N
ATOM 4384 NH2 ARG A 309 11.891 32.006 25.832 1.00 15.18 N
ATOM 4387 C ARG A 309 19.139 31.870 23.213 1.00 14.57 C
ATOM 4388 O ARG A 309 20.288 32.256 23.468 1.00 13.36 O
ATOM 4389 N VAL A 310 18.455 32.367 22.180 1.00 13.70 N
ATOM 4391 CA VAL A 310 19.053 33.390 21.325 1.00 15.05 C
ATOM 4393 CB VAL A 310 18.134 33.596 20.101 1.00 14.71 C
ATOM 4395 CG1 VAL A 310 18.580 34.793 19.258 1.00 18.54 C
ATOM 4399 CG2 VAL A 310 18.121 32.368 19.265 1.00 14.81 C
ATOM 4403 C VAL A 310 19.272 34.671 22.112 1.00 16.45 C
ATOM 4404 O VAL A 310 20.251 35.382 21.905 1.00 15.49 O
ATOM 4405 N LYS A 311 18.316 34.979 22.979 1.00 17.77 N
ATOM 4407 CA LYS A 311 18.415 36.106 23.940 1.00 18.52 C
ATOM 4409 CB LYS A 311 17.942 37.380 23.244 1.00 18.11 C
ATOM 4412 CG LYS A 311 16.677 37.137 22.440 1.00 23.20 C
ATOM 4415 CD LYS A 311 15.574 38.112 22.630 1.00 33.02 C
ATOM 4418 CE LYS A 311 15.667 39.252 21.732 1.00 34.63 C
ATOM 4421 NZ LYS A 311 14.289 39.716 21.277 1.00 36.21 N
ATOM 4425 C LYS A 311 17.532 35.897 25.178 1.00 17.62 C
ATOM 4426 O LYS A 311 16.770 34.912 25.199 1.00 16.50 O
ATOM 4427 OXT LYS A 311 17.534 36.644 26.172 1.00 19.57 O
ATOM 4428 CA CA C 312 28.232 18.547 38.069 1.00 13.89 CA
ATOM 4429 CA CA C 313 17.608 25.091 37.856 1.00 18.60 CA
ATOM 4430 CA CA C 314 27.338 14.925 29.013 0.60 10.25 CA
ATOM 4431 N ALA B 318 2.727 2.475 36.156 1.00 30.60 N
ATOM 4433 CA ALA B 318 2.319 3.152 34.902 1.00 28.10 C
ATOM 4435 CB ALA B 318 1.428 4.295 35.200 1.00 27.75 C
ATOM 4439 C ALA B 318 3.422 3.533 33.900 1.00 24.85 C
ATOM 4440 O ALA B 318 3.103 3.596 32.739 1.00 27.46 O
ATOM 4443 N THR B 319 4.625 3.965 34.273 1.00 24.93 N
ATOM 4445 CA THR B 319 5.658 4.224 33.231 1.00 23.26 C
ATOM 4447 CB THR B 319 6.154 5.690 33.296 1.00 24.03 C
ATOM 4449 OG1 THR B 319 6.811 5.953 34.535 1.00 27.37 O
ATOM 4451 CG2 THR B 319 4.960 6.670 33.258 1.00 27.35 C
ATOM 4455 C THR B 319 6.926 3.305 33.235 1.00 22.75 C
ATOM 4456 O THR B 319 7.820 3.498 32.406 1.00 21.26 O
ATOM 4457 N GLU B 320 7.027 2.401 34.205 1.00 21.07 N
ATOM 4459 CA GLU B 320 8.177 1.559 34.324 1.00 21.49 C
ATOM 4461 CB GLU B 320 9.328 2.280 35.014 1.00 21.67 C
ATOM 4464 CG GLU B 320 8.980 2.681 36.413 1.00 25.74 C
ATOM 4467 CD GLU B 320 10.174 3.130 37.222 1.00 34.05 C
ATOM 4468 OE1 GLU B 320 10.962 3.910 36.698 1.00 36.87 O
ATOM 4469 OE2 GLU B 320 10.295 2.711 38.394 1.00 39.11 O
ATOM 4470 C GLU B 320 7.818 0.308 35.082 1.00 20.20 C
ATOM 4471 O GLU B 320 6.914 0.330 35.945 1.00 20.85 O
ATOM 4472 N TRP B 321 8.526 -0.774 34.748 1.00 18.06 N
ATOM 4474 CA TRP B 321 8.271 -2.092 35.310 1.00 17.54 C
ATOM 4476 CB TRP B 321 7.595 -2.961 34.277 1.00 15.93 C
ATOM 4479 CG TRP B 321 6.265 -2.537 33.906 1.00 18.41 C
ATOM 4480 CD1 TRP B 321 5.089 -3.007 34.445 1.00 16.53 C
ATOM 4482 NE1 TRP B 321 4.017 -2.406 33.836 1.00 19.73 N
ATOM 4484 CE2 TRP B 321 4.470 -1.523 32.886 1.00 15.64 C
ATOM 4485 CD2 TRP B 321 5.889 -1.576 32.903 1.00 15.37 C
ATOM 4486 CE3 TRP B 321 6.596 -0.772 31.992 1.00 14.76 C
ATOM 4488 CZ3 TRP B 321 5.852 0.097 31.140 1.00 17.06 C
ATOM 4490 CH2 TRP B 321 4.428 0.089 31.165 1.00 17.68 C
ATOM 4492 CZ2 TRP B 321 3.757 -0.693 32.047 1.00 18.99 C
ATOM 4494 C TRP B 321 9.570 -2.716 35.728 1.00 16.82 C
ATOM 4495 O TRP B 321 10.068 -36.54 35.131 1.00 16.09 O
ATOM 4496 N PRO B 322 10.186 -2.151 36.755 1.00 18.33 N
ATOM 4497 CA PRO B 322 11.493 -2.628 37.202 1.00 19.01 C
ATOM 4499 CB PRO B 322 11.829 -1.725 38.392 1.00 19.99 C
ATOM 4502 CG PRO B 322 10.556 -1.019 38.744 1.00 19.55 C
ATOM 4505 CD PRO B 322 9.651 -1.061 37.575 1.00 19.07 C
ATOM 4508 C PRO B 322 11.484 -4.065 37.641 1.00 19.86 C
ATOM 4509 O PRO B 322 12.495 -4.748 37.546 1.00 20.25 O
ATOM 4510 N GLU B 323 10.334 -4.557 38.050 1.00 20.04 N
ATOM 4512 CA GLU B 323 10.262 -5.906 38.546 1.00 20.93 C
ATOM 4514 CB GLU B 323 8.960 -6.041 39.331 1.00 23.24 C
ATOM 4517 CG GLU B 323 7.708 -5.954 38.441 1.00 26.81 C
ATOM 4520 CD GLU B 323 7.184 -4.530 38.089 1.00 27.51 C
ATOM 4521 OE1 GLU B 323 7.879 -3.511 38.275 1.00 20.70 O
ATOM 4522 OE2 GLU B 323 5.996 -4.461 37.641 1.00 30.50 O
ATOM 4523 C GLU B 323 10.325 -6.934 37.407 1.00 18.55 C
ATOM 4524 O GLU B 323 10.521 -8.111 37.642 1.00 16.50 O
ATOM 4525 N LEU B 324 10.256 -6.485 36.172 1.00 16.08 N
ATOM 4527 CA LEU B 324 10.357 -7.398 35.050 1.00 15.61 C
ATOM 4529 CB LEU B 324 9.626 -6.849 33.846 1.00 15.54 C
ATOM 4532 CG LEU B 324 8.113 -6.779 34.039 1.00 16.64 C
ATOM 4534 CD1 LEU B 324 7.437 -6.061 32.923 1.00 19.42 C
ATOM 4538 CD2 LEU B 324 7.648 -8.212 34.152 1.00 19.22 C
ATOM 4542 C LEU B 324 11.815 -7.755 34.643 1.00 14.32 C
ATOM 4543 O LEU B 324 12.017 -8.619 33.836 1.00 14.01 O
ATOM 4544 N VAL B 325 12.792 -7.073 35.189 1.00 15.66 N
ATOM 4546 CA VAL B 325 14.180 -7.370 34.816 1.00 15.56 C
ATOM 4548 CB VAL B 325 15.184 -6.410 35.456 1.00 15.71 C
ATOM 4550 CG1 VAL B 325 16.629 -6.860 35.094 1.00 16.62 C
ATOM 4554 CG2 VAL B 325 14.953 -4.946 34.988 1.00 14.67 C
ATOM 4558 C VAL B 325 14.478 -8.817 35.197 1.00 15.70 C
ATOM 4559 O VAL B 325 14.181 -9.219 36.316 1.00 15.01 O
ATOM 4560 N GLY B 326 14.985 -9.609 34.247 1.00 16.26 N
ATOM 4562 CA GLY B 326 15.302 -11.008 34.494 1.00 15.67 C
ATOM 4565 C GLY B 326 14.166 -11.958 34.140 1.00 16.74 C
ATOM 4566 O GLY B 326 14.358 -13.159 34.108 1.00 16.04 O
ATOM 4567 N LYS B 327 12.957 -11.432 33.950 1.00 16.30 N
ATOM 4569 CA LYS B 327 11.848 -12.266 33.510 1.00 17.25 C
ATOM 4571 CB LYS B 327 10.514 -11.632 33.958 1.00 17.70 C
ATOM 4574 CG LYS B 327 10.573 -11.307 35.417 1.00 22.70 C
ATOM 4577 CD LYS B 327 9.217 -11.378 36.140 1.00 30.58 C
ATOM 4580 CE LYS B 327 9.404 -11.302 37.674 1.00 31.61 C
ATOM 4583 NZ LYS B 327 10.674 -11.962 38.027 1.00 33.63 N
ATOM 4587 C LYS B 327 11.837 -12.497 32.021 1.00 16.69 C
ATOM 4588 O LYS B 327 12.479 -11.805 31.222 1.00 15.76 O
ATOM 4589 N SER B 328 11.055 -13.485 31.601 1.00 18.24 N
ATOM 4591 CA SER B 328 10.972 -13.809 30.188 1.00 17.59 C
ATOM 4593 CB SER B 328 10.280 -15.154 29.994 1.00 19.45 C
ATOM 4596 OG SER B 328 8.887 -15.026 30.192 1.00 18.39 O
ATOM 4598 C SER B 328 10.206 -12.757 29.431 1.00 18.63 C
ATOM 4599 O SER B 328 9.375 -12.020 30.003 1.00 17.45 O
ATOM 4600 N VAL B 329 10.494 -12.653 28.140 1.00 18.81 N
ATOM 4602 CA VAL B 329 9.771 -11.690 27.299 1.00 20.52 C
ATOM 4604 CB VAL B 329 10.317 -11.663 25.852 1.00 21.15 C
ATOM 4606 CG1 VAL B 329 9.817 -12.809 25.060 1.00 22.84 C
ATOM 4610 CG2 VAL B 329 9.914 -10.411 25.159 1.00 25.35 C
ATOM 4614 C VAL B 329 8.276 -11.962 27.279 1.00 20.54 C
ATOM 4615 O VAL B 329 7.460 -11.049 27.237 1.00 19.76 O
ATOM 4616 N GLU B 330 7.906 -13.228 27.332 1.00 21.77 N
ATOM 4618 CA GLU B 330 6.504 -13.544 27.379 1.00 22.29 C
ATOM 4620 CB GLU B 330 6.331 -15.048 27.153 1.00 24.60 C
ATOM 4623 CG GLU B 330 6.850 -15.472 25.754 1.00 27.68 C
ATOM 4626 CD GLU B 330 8.341 -15.854 25.674 1.00 35.11 C
ATOM 4627 OE1 GLU B 330 9.141 -15.647 26.617 1.00 28.88 O
ATOM 4628 OE2 GLU B 330 8.722 -16.426 24.632 1.00 41.94 O
ATOM 4629 C GLU B 330 5.809 -13.084 28.642 1.00 22.11 C
ATOM 4630 O GLU B 330 4.676 -12.586 28.584 1.00 21.27 O
ATOM 4631 N GLU B 331 6.452 -13.239 29.790 1.00 21.03 N
ATOM 4633 CA GLU B 331 5.904 -12.751 31.043 1.00 21.48 C
ATOM 4635 CB GLU B 331 6.730 -13.205 32.262 1.00 22.76 C
ATOM 4638 CG GLU B 331 5.844 -13.545 33.454 1.00 31.85 C
ATOM 4641 CD GLU B 331 6.490 -13.408 34.816 1.00 38.17 C
ATOM 4642 OE1 GLU B 331 7.584 -14.024 35.014 1.00 46.35 O
ATOM 4643 OE2 GLU B 331 5.886 -12.712 35.693 1.00 37.37 O
ATOM 4644 C GLU B 331 5.838 -11.243 31.046 1.00 19.51 C
ATOM 4645 O GLU B 331 4.892 -10.668 31.537 1.00 18.89 O
ATOM 4646 N ALA B 332 6.882 -10.609 30.514 1.00 18.18 N
ATOM 4648 CA ALA B 332 6.951 -9.187 30.538 1.00 15.95 C
ATOM 4650 CB ALA B 332 8.254 -8.709 29.931 1.00 16.83 C
ATOM 4654 C ALA B 332 5.801 -8.640 29.757 1.00 15.42 C
ATOM 4655 O ALA B 332 5.163 -7.697 30.182 1.00 14.99 O
ATOM 4656 N LYS B 333 5.580 -9.189 28.589 1.00 15.39 N
ATOM 4658 CA LYS B 333 4.489 -8.693 27.748 1.00 17.34 C
ATOM 4660 CB LYS B 333 4.458 -9.450 26.441 1.00 17.67 C
ATOM 4663 CG LYS B 333 5.438 -9.004 25.401 1.00 21.32 C
ATOM 4666 CD LYS B 333 5.200 -9.807 24.128 1.00 23.42 C
ATOM 4669 CE LYS B 333 6.357 -9.619 23.113 1.00 28.93 C
ATOM 4672 NZ LYS B 333 6.005 -10.290 21.820 1.00 28.19 N
ATOM 4676 C LYS B 333 3.127 -8.789 28.452 1.00 17.99 C
ATOM 4677 O LYS B 333 2.338 -7.868 28.410 1.00 15.95 O
ATOM 4678 N LYS B 334 2.858 -9.904 29.125 1.00 19.30 N
ATOM 4680 CA LYS B 334 1.595 -10.046 29.842 1.00 19.86 C
ATOM 4682 CB LYS B 334 1.417 -11.432 30.481 1.00 21.24 C
ATOM 4685 CG LYS B 334 0.949 -12.476 29.568 1.00 28.52 C
ATOM 4688 CD LYS B 334 0.499 -13.819 30.317 1.00 33.48 C
ATOM 4691 CE LYS B 334 0.650 -15.022 29.319 1.00 37.14 C
ATOM 4694 NZ LYS B 334 0.870 -14.604 27.850 1.00 36.97 N
ATOM 4698 C LYS B 334 1.457 -8.983 30.890 1.00 18.97 C
ATOM 4699 O LYS B 334 0.386 -8.343 31.021 1.00 16.86 O
ATOM 4700 N VAL B 335 2.522 -8.754 31.658 1.00 16.84 N
ATOM 4702 CA VAL B 335 2.480 -7.783 32.726 1.00 16.65 C
ATOM 4704 CB VAL B 335 3.743 -7.823 33.591 1.00 15.76 C
ATOM 4706 CG1 VAL B 335 3.817 -6.655 34.612 1.00 19.24 C
ATOM 4710 CG2 VAL B 335 3.789 -9.108 34.341 1.00 17.38 C
ATOM 4714 C VAL B 335 2.288 -6.382 32.203 1.00 15.76 C
ATOM 4715 O VAL B 335 1.494 -5.615 32.763 1.00 16.18 O
ATOM 4716 N ILE B 336 3.033 -6.023 31.167 1.00 15.08 N
ATOM 4718 CA ILE B 336 2.903 -4.703 30.635 1.00 14.79 C
ATOM 4720 CB ILE B 336 3.967 -4.441 29.592 1.00 14.82 C
ATOM 4722 CG1 ILE B 336 5.290 -4.318 30.367 1.00 16.31 C
ATOM 4725 CD1 ILE B 336 6.479 -4.602 29.579 1.00 19.31 C
ATOM 4729 CG2 ILE B 336 3.543 -3.266 28.733 1.00 16.34 C
ATOM 4733 C ILE B 336 1.508 -4.472 30.074 1.00 15.10 C
ATOM 4734 O ILE B 336 0.914 -3.437 30.347 1.00 16.57 O
ATOM 4735 N LEU B 337 0.956 -5.456 29.390 1.00 15.14 N
ATOM 4737 CA LEU B 337 -0.343 -5.235 28.769 1.00 15.94 C
ATOM 4739 CB LEU B 337 -0.645 -6.290 27.727 1.00 15.77 C
ATOM 4742 CG LEU B 337 0.121 -6.195 26.404 1.00 13.58 C
ATOM 4744 CD1 LEU B 337 0.021 -7.498 25.632 1.00 15.44 C
ATOM 4748 CD2 LEU B 337 -0.350 -5.049 25.553 1.00 17.85 C
ATOM 4752 C LEU B 337 -1.450 -5.146 29.810 1.00 17.57 C
ATOM 4753 O LEU B 337 -2.511 -4.531 29.544 1.00 17.36 O
ATOM 4754 N GLN B 338 -1.210 -5.702 30.985 1.00 18.09 N
ATOM 4756 CA GLN B 338 -2.195 -5.610 32.047 1.00 21.31 C
ATOM 4758 CB GLN B 338 -1.830 -6.557 33.205 1.00 21.97 C
ATOM 4761 CG GLN B 338 -1.842 -8.050 32.775 1.00 26.01 C
ATOM 4764 CD GLN B 338 -1.562 -9.127 33.893 1.00 29.25 C
ATOM 4765 OE1 GLN B 338 -0.720 -8.942 34.831 1.00 34.90 O
ATOM 4766 NE2 GLN B 338 -2.211 -10.262 33.738 1.00 29.07 N
ATOM 4769 C GLN B 338 -2.398 -4.143 32.469 1.00 22.67 C
ATOM 4770 O GLN B 338 -3.530 -3.694 32.741 1.00 22.11 O
ATOM 4771 N ASP B 339 -1.318 -3.366 32.465 1.00 21.30 N
ATOM 4773 CA ASP B 339 -1.377 -1.936 32.761 1.00 21.98 C
ATOM 4775 CB ASP B 339 -0.047 -1.478 33.381 1.00 22.85 C
ATOM 4778 CG ASP B 339 0.213 -2.106 34.710 1.00 26.72 C
ATOM 4779 OD1 ASP B 339 -0.740 -2.105 35.518 1.00 33.25 O
ATOM 4780 OD2 ASP B 339 1.269 -2.680 35.026 1.00 26.47 O
ATOM 4781 C ASP B 339 -1.644 -1.066 31.555 1.00 22.06 C
ATOM 4782 O ASP B 339 -2.247 0.004 31.667 1.00 23.60 O
ATOM 4783 N LYS B 340 -1.218 -1.515 30.387 1.00 19.19 N
ATOM 4785 CA LYS B 340 -1.226 -0.722 29.218 1.00 18.98 C
ATOM 4787 CB LYS B 340 0.186 -0.070 29.118 1.00 18.88 C
ATOM 4790 CG LYS B 340 0.345 0.901 28.024 1.00 18.59 C
ATOM 4793 CD LYS B 340 1.805 1.491 28.014 1.00 19.17 C
ATOM 4796 CE LYS B 340 1.999 2.462 26.848 1.00 20.90 C
ATOM 4799 NZ LYS B 340 1.137 3.683 27.041 1.00 23.19 N
ATOM 4803 C LYS B 340 -1.611 -1.550 28.035 1.00 18.75 C
ATOM 4804 O LYS B 340 -0.822 -1.920 27.224 1.00 18.54 O
ATOM 4805 N PRO B 341 -2.906 -1.822 27.892 1.00 17.67 N
ATOM 4806 CA PRO B 341 -3.391 -2.768 26.911 1.00 17.68 C
ATOM 4808 CB PRO B 341 -4.926 -2.753 27.108 1.00 18.59 C
ATOM 4811 CG PRO B 341 -5.155 -1.955 28.331 1.00 19.20 C
ATOM 4814 CD PRO B 341 -3.919 -1.347 28.825 1.00 20.06 C
ATOM 4817 C PRO B 341 -3.101 -2.444 25.491 1.00 15.31 C
ATOM 4818 O PRO B 341 -3.022 -3.289 24.614 1.00 19.02 O
ATOM 4819 N GLU B 342 -2.986 -1.143 25.254 1.00 17.33 N
ATOM 4821 CA GLU B 342 -2.745 -0.687 23.906 1.00 17.70 C
ATOM 4823 CB GLU B 342 -3.615 0.545 23.555 1.00 20.27 C
ATOM 4826 CG GLU B 342 -5.028 0.042 23.191 1.00 21.84 C
ATOM 4829 CD GLU B 342 -6.029 1.135 22.803 1.00 30.03 C
ATOM 4830 OE1 GLU B 342 -5.646 2.108 22.127 1.00 34.62 O
ATOM 4831 OE2 GLU B 342 -7.217 0.982 23.131 1.00 29.42 O
ATOM 4832 C GLU B 342 -1.232 -0.491 23.581 1.00 17.99 C
ATOM 4833 O GLU B 342 -0.912 -0.071 22.473 1.00 17.45 O
ATOM 4834 N ALA B 343 -0.348 -0.902 24.474 1.00 18.01 N
ATOM 4836 CA ALA B 343 1.075 -0.825 24.187 1.00 17.75 C
ATOM 4838 CB ALA B 343 1.886 -1.320 25.374 1.00 17.76 C
ATOM 4842 C ALA B 343 1.501 -1.509 22.934 1.00 18.41 C
ATOM 4843 O ALA B 343 1.018 -2.612 22.539 1.00 16.39 O
ATOM 4844 N GLN B 344 2.398 -0.808 22.223 1.00 16.93 N
ATOM 4846 CA GLN B 344 3.007 -1.326 21.061 1.00 16.94 C
ATOM 4848 CB GLN B 344 3.197 -0.264 19.951 1.00 18.67 C
ATOM 4851 CG GLN B 344 1.915 0.367 19.450 1.00 22.45 C
ATOM 4854 CD GLN B 344 1.041 -0.668 18.836 1.00 23.74 C
ATOM 4855 OE1 GLN B 344 1.336 -1.176 17.737 1.00 28.25 O
ATOM 4856 NE2 GLN B 344 0.022 -1.076 19.570 1.00 24.17 N
ATOM 4859 C GLN B 344 4.371 -1.804 21.578 1.00 16.61 C
ATOM 4860 O GLN B 344 5.276 -0.987 21.833 1.00 15.55 O
ATOM 4861 N ILE B 345 4.503 -3.109 21.745 1.00 14.81 N
ATOM 4863 CA ILE B 345 5.747 -3.697 22.338 1.00 15.57 C
ATOM 4865 CB ILE B 345 5.426 -4.864 23.229 1.00 14.52 C
ATOM 4867 CG1 ILE B 345 4.420 -4.437 24.307 1.00 16.03 C
ATOM 4870 CD1 ILE B 345 4.237 -5.385 25.452 1.00 21.70 C
ATOM 4874 CG2 ILE B 345 6.683 -5.445 23.832 1.00 18.60 C
ATOM 4878 C ILE B 345 6.713 -4.108 21.261 1.00 15.60 C
ATOM 4879 O ILE B 345 6.317 -4.759 20.335 1.00 14.53 O
ATOM 4880 N ILE B 346 7.947 -3.618 21.338 1.00 15.09 N
ATOM 4882 CA ILE B 346 9.006 -3.853 20.373 1.00 17.65 C
ATOM 4884 CB ILE B 346 9.607 -2.448 19.887 1.00 18.73 C
ATOM 4886 CG1ILE B 346 8.486 -1.515 19.488 1.00 25.44 C
ATOM 4889 CD1ILE B 346 7.656 -2.110 18.400 1.00 27.09 C
ATOM 4893 CG2ILE B 346 10.538 -2.639 18.736 1.00 24.66 C
ATOM 4897 C ILE B 346 10.126 -4.549 21.136 1.00 15.44 C
ATOM 4898 O ILE B 346 10.515 -4.048 22.174 1.00 15.03 O
ATOM 4899 N VAL B 347 10.621 -5.685 20.637 1.00 15.30 N
ATOM 4901 CA VAL B 347 11.701 -6.425 21.310 1.00 14.26 C
ATOM 4903 CB VAL B 347 11.363 -7.916 21.411 1.00 13.95 C
ATOM 4905 CG1VAL B 347 12.550 -8.744 21.949 1.00 15.52 C
ATOM 4909 CG2VAL B 347 10.056 -8.103 22.171 1.00 16.01 C
ATOM 4913 C VAL B 347 12.980 -6.253 20.518 1.00 13.34 C
ATOM 4914 O VAL B 347 12.999 -6.387 19.275 1.00 13.71 O
ATOM 4915 N LEU B 348 14.025 -5.824 21.225 1.00 13.58 N
ATOM 4917 CA LEU B 348 15.334 -5.595 20.654 1.00 14.50 C
ATOM 4919 CB LEU B 348 15.629 -4.101 20.619 1.00 14.73 C
ATOM 4922 CG LEU B 348 14.624 -3.255 19.836 1.00 18.66 C
ATOM 4924 CD1LEU B 348 14.885 -1.758 20.172 1.00 20.34 C
ATOM 4928 CD2LEU B 348 14.781 -3.515 18.370 1.00 21.48 C
ATOM 4932 C LEU B 348 16.420 -6.246 21.500 1.00 13.69 C
ATOM 4933 O LEU B 348 16.298 -6.400 22.715 1.00 12.97 O
ATOM 4934 N PRO B 349 17.533 -6.626 20.864 1.00 13.80 N
ATOM 4935 CA PRO B 349 18.630 -7.173 21.635 1.00 12.71 C
ATOM 4937 CB PRO B 349 19.686 -7.528 20.564 1.00 14.22 C
ATOM 4940 CG PRO B 349 18.940 -7.614 19.288 1.00 17.12 C
ATOM 4943 CD PRO B 349 17.802 -6.586 19.422 1.00 13.86 C
ATOM 4946 C PRO B 349 19.238 -6.154 22.603 1.00 12.67 C
ATOM 4947 O PRO B 349 19.358 -4.987 22.270 1.00 10.43 O
ATOM 4948 N VAL B 350 19.679 -6.629 23.756 1.00 10.88 N
ATOM 4950 CA VAL B 350 20.463 -5.844 24.676 1.00 11.84 C
ATOM 4952 CB VAL B 350 20.967 -6.740 25.861 1.00 12.85 C
ATOM 4954 CG1VAL B 350 21.918 -7.822 25.385 1.00 14.03 C
ATOM 4958 CG2VAL B 350 21.614 -5.822 26.921 1.00 13.28 C
ATOM 4962 C VAL B 350 21.627 -5.189 23.892 1.00 10.88 C
ATOM 4963 O VAL B 350 22.262 -5.815 23.000 1.00 10.87 O
ATOM 4964 N GLY B 351 21.864 -3.926 24.205 1.00 11.86 N
ATOM 4966 CA GLY B 351 22.882 -3.099 23.581 1.00 11.51 C
ATOM 4969 C GLY B 351 22.512 -2.331 22.313 1.00 12.47 C
ATOM 4970 O GLY B 351 23.335 -1.618 21.744 1.00 10.98 O
ATOM 4971 N THR B 352 21.315 -2.561 21.822 1.00 11.64 N
ATOM 4973 CA THR B 352 20.841 -1.861 20.642 1.00 11.92 C
ATOM 4975 CB THR B 352 19.508 -2.419 20.225 1.00 13.71 C
ATOM 4977 OG1THR B 352 19.641 -3.812 19.860 1.00 10.89 O
ATOM 4979 CG2THR B 352 18.993 -1.703 18.981 1.00 12.02 C
ATOM 4983 C THR B 352 20.720 -0.333 20.920 1.00 11.24 C
ATOM 4984 O THR B 352 20.235 0.015 21.976 1.00 12.17 O
ATOM 4985 N ILE B 353 21.218 0.435 20.012 1.00 11.34 N
ATOM 4987 CA ILE B 353 21.125 1.893 20.166 1.00 11.58 C
ATOM 4989 CB ILE B 353 22.322 2.605 19.504 1.00 13.21 C
ATOM 4991 CG1 ILE B 353 23.642 2.014 19.992 1.00 11.55 C
ATOM 4994 CD1 ILE B 353 23.795 1.980 21.496 1.00 15.61 C
ATOM 4998 CG2 ILE B 353 22.294 4.098 19.802 1.00 13.36 C
ATOM 5002 C ILE B 353 19.828 2.332 19.509 1.00 11.44 C
ATOM 5003 O ILE B 353 19.485 1.827 18.417 1.00 11.02 O
ATOM 5004 N VAL B 354 19.136 3.268 20.180 1.00 10.73 N
ATOM 5006 CA VAL B 354 17.785 3.663 19.740 1.00 11.42 C
ATOM 5008 CB VAL B 354 16.693 3.043 20.663 1.00 11.30 C
ATOM 5010 CG1 VAL B 354 16.741 1.521 20.568 1.00 11.88 C
ATOM 5014 CG2 VAL B 354 16.873 3.542 22.103 1.00 12.49 C
ATOM 5018 C VAL B 354 17.558 5.152 19.702 1.00 10.76 C
ATOM 5019 O VAL B 354 18.289 5.918 20.294 1.00 11.15 O
ATOM 5020 N THR B 355 16.607 5.599 18.894 1.00 10.94 N
ATOM 5022 CA THR B 355 16.207 7.001 18.884 1.00 12.16 C
ATOM 5024 CB THR B 355 15.004 7.267 17.939 1.00 13.72 C
ATOM 5026 OG1 THR B 355 13.885 6.481 18.413 1.00 16.24 O
ATOM 5028 CG2 THR B 355 15.313 6.840 16.561 1.00 14.33 C
ATOM 5032 C THR B 355 15.684 7.378 20.254 1.00 12.37 C
ATOM 5033 O THR B 355 15.263 6.554 21.050 1.00 11.43 O
ATOM 5034 N MET B 356 15.787 8.659 20.540 1.00 12.52 N
ATOM 5036 CA MET B 356 15.258 9.222 21.775 1.00 11.53 C
ATOM 5038 CB MET B 356 16.311 10.075 22.468 1.00 11.42 C
ATOM 5041 CG MET B 356 17.427 9.202 23.035 1.00 12.95 C
ATOM 5044 SD MET B 356 16.825 8.040 24.219 1.00 15.08 S
ATOM 5045 CE MET B 356 17.963 6.799 24.107 1.00 20.89 C
ATOM 5049 C MET B 356 13.952 9.961 21.568 1.00 13.71 C
ATOM 5050 O MET B 356 13.675 11.024 22.215 1.00 12.74 O
ATOM 5051 N GLU B 357 13.148 9.417 20.659 1.00 14.50 N
ATOM 5053 CA GLU B 357 11.765 9.869 20.543 1.00 14.30 C
ATOM 5055 CB GLU B 357 11.135 9.357 19.210 1.00 15.52 C
ATOM 5058 CG GLU B 357 9.674 9.735 19.153 1.00 15.25 C
ATOM 5061 CD GLU B 357 8.947 9.187 17.960 1.00 18.46 C
ATOM 5062 OE1 GLU B 357 7.768 9.559 17.802 1.00 19.97 O
ATOM 5063 OE2 GLU B 357 9.543 8.377 17.237 1.00 20.59 O
ATOM 5064 C GLU B 357 11.001 9.282 21.703 1.00 14.50 C
ATOM 5065 O GLU B 357 11.233 8.123 22.030 1.00 14.99 O
ATOM 5066 N TYR B 358 10.129 10.074 22.335 1.00 13.93 N
ATOM 5068 CA TYR B 358 9.207 9.612 23.363 1.00 14.38 C
ATOM 5070 CB TYR B 358 9.026 10.601 24.499 1.00 14.43 C
ATOM 5073 CG TYR B 358 8.057 10.136 25.563 1.00 12.84 C
ATOM 5074 CD1 TYR B 358 8.436 9.165 26.487 1.00 14.52 C
ATOM 5076 CE1 TYR B 358 7.559 8.706 27.463 1.00 19.65 C
ATOM 5078 CZ TYR B 358 6.266 9.240 27.504 1.00 19.95 C
ATOM 5079 OH TYR B 358 5.321 8.903 28.447 1.00 26.07 O
ATOM 5081 CE2 TYR B 358 5.873 10.184 26.607 1.00 16.96 C
ATOM 5083 CD2 TYR B 358 6.767 10.650 25.643 1.00 18.09 C
ATOM 5085 C TYR B 358 7.867 9.326 22.712 1.00 15.23 C
ATOM 5086 O TYR B 358 7.142 10.261 22.340 1.00 14.02 O
ATOM 5087 N ARG B 359 7.551 8.048 22.606 1.00 15.15 N
ATOM 5089 CA ARG B 359 6.294 7.557 22.003 1.00 16.88 C
ATOM 5091 CB ARG B 359 6.615 6.465 20.998 1.00 18.79 C
ATOM 5094 CG ARG B 359 6.824 6.884 19.703 1.00 22.92 C
ATOM 5097 CD ARG B 359 6.435 5.794 18.692 1.00 25.80 C
ATOM 5100 NE ARG B 359 7.237 6.083 17.556 1.00 25.82 N
ATOM 5102 CZ ARG B 359 7.515 5.241 16.593 1.00 26.84 C
ATOM 5103 NH1 ARG B 359 7.000 3.996 16.593 1.00 26.53 N
ATOM 5106 NH2 ARG B 359 8.297 5.668 15.627 1.00 28.90 N
ATOM 5109 CA RG B 359 5.449 6.946 23.095 1.00 17.14 C
ATOM 5110 O ARG B 359 5.767 5.861 23.625 1.00 15.98 O
ATOM 5111 N ILE B 360 4.401 7.656 23.504 1.00 16.16 N
ATOM 5113 CA ILE B 360 3.633 7.262 24.670 1.00 17.53 C
ATOM 5115 CB ILE B 360 2.575 8.354 24.998 1.00 17.66 C
ATOM 5117 CG1 ILE B 360 1.895 8.067 26.333 1.00 24.45 C
ATOM 5120 CD1 ILE B 360 1.711 9.278 27.140 1.00 28.72 C
ATOM 5124 CG2 ILE B 360 1.506 8.417 23.930 1.00 18.76 C
ATOM 5128 C ILE B 360 2.947 5.899 24.595 1.00 16.17 C
ATOM 5129 O ILE B 360 2.649 5.307 25.629 1.00 19.59 O
ATOM 5130 N ASP B 361 2.692 5.431 23.402 1.00 19.19 N
ATOM 5132 CA ASP B 361 2.049 4.131 23.290 1.00 20.04 C
ATOM 5134 CB ASP B 361 1.070 4.141 22.156 1.00 22.33 C
ATOM 5137 CG ASP B 361 -0.210 4.932 22.509 1.00 27.91 C
ATOM 5138 OD1 ASP B 361 -0.701 4.823 23.693 1.00 33.70 O
ATOM 5139 OD2 ASP B 361 -0.734 5.711 21.687 1.00 38.62 O
ATOM 5140 C ASP B 361 3.025 2.996 23.111 1.00 19.38 C
ATOM 5141 O ASP B 361 2.580 1.872 22.958 1.00 18.79 O
ATOM 5142 N ARG B 362 4.342 3.291 23.099 1.00 15.34 N
ATOM 5144 CA ARG B 362 5.342 2.241 22.870 1.00 15.87 C
ATOM 5146 CB ARG B 362 6.480 2.793 21.992 1.00 13.90 C
ATOM 5149 CG ARG B 362 7.657 1.839 21.867 1.00 16.63 C
ATOM 5152 CD ARG B 362 8.570 2.234 20.721 1.00 16.00 C
ATOM 5155 NE ARG B 362 9.204 3.494 21.085 1.00 15.40 N
ATOM 5157 CZ ARG B 362 9.808 4.315 20.234 1.00 14.22 C
ATOM 5158 NH1 ARG B 362 9.893 4.014 18.939 1.00 16.86 N
ATOM 5161 NH2 ARG B 362 10.295 5.449 20.686 1.00 14.53 N
ATOM 5164 C ARG B 362 5.970 1.737 24.163 1.00 14.75 C
ATOM 5165 O ARG B 362 6.130 2.504 25.117 1.00 13.39 O
ATOM 5166 N VAL B 363 6.285 0.467 24.199 1.00 13.88 N
ATOM 5168 CA VAL B 363 7.159 -0.094 25.241 1.00 14.50 C
ATOM 5170 CB VAL B 363 6.448 -0.910 26.349 1.00 14.42 C
ATOM 5172 CG1 VAL B 363 7.477 -1.351 27.372 1.00 17.68 C
ATOM 5176 CG2 VAL B 363 5.401 -0.069 27.015 1.00 16.62 C
ATOM 5180 C VAL B 363 8.230 -0.943 24.576 1.00 14.33 C
ATOM 5181 O VAL B 363 7.928 -1.989 23.984 1.00 14.74 O
ATOM 5182 N ARG B 364 9.483 -0.510 24.651 1.00 13.57 N
ATOM 5184 CA ARG B 364 10.570 -1.349 24.131 1.00 13.59 C
ATOM 5186 CB ARG B 364 11.753 -0.458 23.713 1.00 12.88 C
ATOM 5189 CG ARG B 364 11.565 0.380 22.482 1.00 14.21 C
ATOM 5192 CD ARG B 364 12.671 1.411 22.216 1.00 18.75 C
ATOM 5195 NE ARG B 364 12.606 2.066 20.950 1.00 16.44 N
ATOM 5197 CZ ARG B 364 13.123 3.278 20.638 1.00 18.34 C
ATOM 5198 NH1 ARG B 364 13.591 4.073 21.531 1.00 21.95 N
ATOM 5201 NH2 ARG B 364 13.073 3.670 19.412 1.00 23.97 N
ATOM 5204 C ARG B 364 11.046 -2.339 25.177 1.00 14.09 C
ATOM 5205 O ARG B 364 11.154 -1.994 26.361 1.00 16.64 O
ATOM 5206 N LEU B 365 11.340 -3.548 24.735 1.00 13.84 N
ATOM 5208 CA LEU B 365 11.904 -4.519 25.617 1.00 12.64 C
ATOM 5210 CB LEU B 365 11.017 -5.737 25.667 1.00 14.17 C
ATOM 5213 CG LEU B 365 9.653 -5.571 26.305 1.00 14.30 C
ATOM 5215 CD1 LEU B 365 8.907 -6.860 26.267 1.00 17.46 C
ATOM 5219 CD2 LEU B 365 9.813 -5.054 27.714 1.00 18.97 C
ATOM 5223 C LEU B 365 13.235 -4.929 25.065 1.00 13.48 C
ATOM 5224 O LEU B 365 13.307 -5.386 23.919 1.00 13.99 O
ATOM 5225 N PHE B 366 14.271 -4.775 25.887 1.00 12.70 N
ATOM 5227 CA PHE B 366 15.619 -5.176 25.533 1.00 12.04 C
ATOM 5229 CB PHE B 366 16.651 -4.148 25.971 1.00 12.03 C
ATOM 5232 CG PHE B 366 16.476 -2.809 25.291 1.00 13.71 C
ATOM 5233 CD1 PHE B 366 15.591 -1.889 25.820 1.00 13.42 C
ATOM 5235 CE1 PHE B 366 15.373 -0.702 25.229 1.00 16.78 C
ATOM 5237 CZ PHE B 366 16.025 -0.376 24.078 1.00 16.52 C
ATOM 5239 CE2 PHE B 366 16.899 -1.322 23.444 1.00 15.87 C
ATOM 5241 CD2 PHE B 366 17.121 -2.554 24.083 1.00 15.60 C
ATOM 5243 C PHE B 366 15.875 -6.502 26.202 1.00 13.03 C
ATOM 5244 O PHE B 366 15.700 -6.682 27.407 1.00 13.72 O
ATOM 5245 N VAL B 367 16.319 -7.448 25.407 1.00 13.72 N
ATOM 5247 CA VAL B 367 16.457 -8.824 25.906 1.00 14.35 C
ATOM 5249 CB VAL B 367 15.408 -9.719 25.263 1.00 15.42 C
ATOM 5251 CG1 VAL B 367 13.988 -9.325 25.626 1.00 17.97 C
ATOM 5255 CG2 VAL B 367 15.608 -9.853 23.736 1.00 13.87 C
ATOM 5259 C VAL B 367 17.829 -9.418 25.654 1.00 14.47 C
ATOM 5260 O VAL B 367 18.508 -9.099 24.686 1.00 13.82 O
ATOM 5261 N ASP B 368 18.186 -10.385 26.500 1.00 15.21 N
ATOM 5263 CA ASP B 368 19.421 -11.145 26.337 1.00 14.26 C
ATOM 5265 CB ASP B 368 20.020 -11.526 27.668 1.00 12.83 C
ATOM 5268 CG ASP B 368 19.168 -12.492 28.461 1.00 13.78 C
ATOM 5269 OD1 ASP B 368 18.383 -13.277 27.864 1.00 15.03 O
ATOM 5270 OD2 ASP B 368 19.284 -12.487 29.687 1.00 14.11 O
ATOM 5271 C ASP B 368 19.197 -12.347 25.438 1.00 15.37 C
ATOM 5272 O ASP B 368 18.090 -12.572 24.940 1.00 13.77 O
ATOM 5273 N LYS B 369 20.201 -13.219 25.295 1.00 15.53 N
ATOM 5275 CA LYS B 369 20.096 -14.274 24.320 1.00 16.17 C
ATOM 5277 CB LYS B 369 21.492 -14.913 24.031 1.00 18.57 C
ATOM 5280 CG LYS B 369 22.335 -14.040 23.132 1.00 23.43 C
ATOM 5283 CD LYS B 369 21.692 -13.930 21.723 1.00 33.33 C
ATOM 5286 CE LYS B 369 21.825 -15.245 20.863 1.00 37.24 C
ATOM 5289 NZ LYS B 369 20.834 -15.304 19.703 1.00 39.15 N
ATOM 5293 C LYS B 369 19.120 -15.342 24.746 1.00 17.09 C
ATOM 5294 O LYS B 369 18.736 -16.166 23.914 1.00 16.83 O
ATOM 5295 N LEU B 370 18.744 -15.352 26.029 1.00 15.51 N
ATOM 5297 CA LEU B 370 17.739 -16.298 26.509 1.00 15.40 C
ATOM 5299 CB LEU B 370 18.053 -16.814 27.899 1.00 15.53 C
ATOM 5302 CG LEU B 370 19.358 -17.657 28.054 1.00 17.89 C
ATOM 5304 CD1 LEU B 370 19.624 -17.980 29.490 1.00 16.28 C
ATOM 5308 CD2 LEU B 370 19.237 -18.944 27.314 1.00 17.77 C
ATOM 5312 C LEU B 370 16.346 -15.711 26.481 1.00 17.02 C
ATOM 5313 O LEU B 370 15.426 -16.340 27.005 1.00 16.78 O
ATOM 5314 N ASP B 371 16.191 -14.538 25.884 1.00 15.62 N
ATOM 5316 CA ASP B 371 14.909 -13.828 25.822 1.00 17.82 C
ATOM 5318 CB ASP B 371 13.844 -14.610 25.070 1.00 16.70 C
ATOM 5321 CG ASP B 371 13.943 -14.455 23.561 1.00 26.05 C
ATOM 5322 OD1 ASP B 371 14.579 -13.492 23.026 1.00 26.78 O
ATOM 5323 OD2 ASP B 371 13.333 -15.252 22.835 1.00 35.44 O
ATOM 5324 C ASP B 371 14.392 -13.390 27.197 1.00 16.31 C
ATOM 5325 O ASP B 371 13.179 -13.251 27.432 1.00 15.98 O
ATOM 5326 N ASN B 372 15.334 -13.152 28.115 1.00 14.12 N
ATOM 5328 CA ASN B 372 15.057 -12.509 29.380 1.00 13.45 C
ATOM 5330 CB ASN B 372 15.846 -13.137 30.518 1.00 14.25 C
ATOM 5333 CG ASN B 372 15.359 -14.530 30.868 1.00 17.78 C
ATOM 5334 OD1 ASN B 372 14.170 -14.830 30.726 1.00 15.50 O
ATOM 5335 ND2 ASN B 372 16.280 -15.394 31.268 1.00 15.27 N
ATOM 5338 C ASN B 372 15.328 -11.025 29.328 1.00 13.56 C
ATOM 5339 O ASN B 372 16.185 -10.535 28.526 1.00 12.51 O
ATOM 5340 N ILE B 373 14.521 -10.271 30.078 1.00 12.00 N
ATOM 5342 CA ILE B 373 14.595 -8.793 30.098 1.00 12.80 C
ATOM 5344 CB ILE B 373 13.409 -8.177 30.868 1.00 12.48 C
ATOM 5346 CG1 ILE B 373 12.115 -8.624 30.263 1.00 14.38 C
ATOM 5349 CD1 ILE B 373 12.021 -8.386 28.913 1.00 13.59 C
ATOM 5353 CG2 ILE B 373 13.467 -6.685 30.862 1.00 13.18 C
ATOM 5357 C ILE B 373 15.888 -8.319 30.716 1.00 12.70 C
ATOM 5358 O ILE B 373 16.217 -8.667 31.872 1.00 13.25 O
ATOM 5359 N ALA B 374 16.619 -7.490 29.940 1.00 12.49 N
ATOM 5361 CA ALA B 374 17.962 -7.065 30.334 1.00 11.98 C
ATOM 5363 CB ALA B 374 18.894 -6.974 29.099 1.00 11.19 C
ATOM 5367 C ALA B 374 18.005 -5.723 31.031 1.00 12.88 C
ATOM 5368 O ALA B 374 19.017 -5.394 31.640 1.00 13.61 O
ATOM 5369 N GLU B 375 16.957 -4.922 30.954 1.00 12.63 N
ATOM 5371 CA GLU B 375 16.927 -3.628 31.592 1.00 11.71 C
ATOM 5373 CB GLU B 375 17.669 -2.571 30.740 1.00 13.04 C
ATOM 5376 CG GLU B 375 17.020 -2.247 29.443 1.00 13.36 C
ATOM 5379 CD GLU B 375 17.854 -1.238 28.611 1.00 16.47 C
ATOM 5380 OE1 GLU B 375 18.961 -1.591 28.279 1.00 19.52 O
ATOM 5381 OE2 GLU B 375 17.355 -0.152 28.242 1.00 18.89 O
ATOM 5382 C GLU B 375 15.464 -3.195 31.858 1.00 12.84 C
ATOM 5383 O GLU B 375 14.563 -3.750 31.276 1.00 12.27 O
ATOM 5384 N VAL B 376 15.277 -2.235 32.747 1.00 12.90 N
ATOM 5386 CA VAL B 376 13.918 -1.872 33.175 1.00 13.25 C
ATOM 5388 CB VAL B 376 13.941 -0.719 34.173 1.00 13.63 C
ATOM 5390 CG1 VAL B 376 12.515 -0.240 34.514 1.00 15.72 C
ATOM 5394 CG2 VAL B 376 14.681 -1.129 35.424 1.00 19.49 C
ATOM 5398 C VAL B 376 13.110 -1.441 32.018 1.00 12.36 C
ATOM 5399 O VAL B 376 13.458 -0.494 31.358 1.00 12.35 O
ATOM 5400 N PRO B 377 12.016 -2.117 31.700 1.00 13.27 N
ATOM 5401 CA PRO B 377 11.169 -1.588 30.649 1.00 14.34 C
ATOM 5403 CB PRO B 377 10.141 -2.697 30.437 1.00 15.95 C
ATOM 5406 CG PRO B 377 10.777 -3.950 31.039 1.00 13.76 C
ATOM 5409 CD PRO B 377 11.585 -3.453 32.170 1.00 13.52 C
ATOM 5412 C PRO B 377 10.472 -0.302 31.046 1.00 14.46 C
ATOM 5413 O PRO B 377 10.078 -0.158 32.190 1.00 14.50 O
ATOM 5414 N ARG B 378 10.291 0.603 30.087 1.00 14.99 N
ATOM 5416 CA ARG B 378 9.687 1.912 30.298 1.00 14.79 C
ATOM 5418 CB ARG B 378 10.756 3.004 30.386 1.00 14.41 C
ATOM 5421 CG ARG B 378 11.717 2.809 31.542 1.00 16.49 C
ATOM 5424 CD ARG B 378 12.848 3.892 31.600 1.00 17.97 C
ATOM 5427 NE ARG B 378 13.805 3.569 32.642 1.00 15.14 N
ATOM 5429 CZ ARG B 378 13.602 3.673 33.949 1.00 19.35 C
ATOM 5430 NH1 ARG B 378 12.452 4.173 34.445 1.00 21.30 N
ATOM 5433 NH2 ARG B 378 14.548 3.250 34.752 1.00 20.05 N
ATOM 5436 C ARG B 378 8.797 2.263 29.129 1.00 14.34 C
ATOM 5437 O ARG B 378 8.974 1.810 28.013 1.00 14.31 O
ATOM 5438 N VAL B 379 7.801 3.052 29.411 1.00 13.60 N
ATOM 5440 CA VAL B 379 7.028 3.650 28.358 1.00 14.99 C
ATOM 5442 CB VAL B 379 5.847 4.399 28.967 1.00 16.05 C
ATOM 5444 CG1 VAL B 379 5.148 5.163 27.928 1.00 17.97 C
ATOM 5448 CG2 VAL B 379 4.863 3.410 29.606 1.00 19.07 C
ATOM 5452 C VAL B 379 7.899 4.629 27.551 1.00 13.40 C
ATOM 5453 O VAL B 379 8.683 5.397 28.127 1.00 13.64 O
ATOM 5454 N GLY B 380 7.742 4.666 26.241 1.00 13.02 N
ATOM 5456 CA GLY B 380 8.480 5.637 25.459 1.00 14.94 C
ATOM 5459 C GLY B 380 8.968 5.181 24.107 1.00 13.89 C
ATOM 5460 O GLY B 380 8.939 3.974 23.839 1.00 13.82 O
ATOM 5461 OXT GLY B 380 9.391 6.068 23.366 1.00 15.44 O
ATOM 5462 O HOH W 1 26.337 16.956 29.710 1.00 8.65 O
ATOM 5465 O HOH W 2 9.939 2.105 25.538 1.00 12.99 O
ATOM 5468 O HOH W 3 22.328 10.101 24.400 1.00 12.55 O
ATOM 5471 O HOH W 4 30.572 18.292 23.118 1.00 9.33 O
ATOM 5474 O HOH W 5 8.147 23.150 18.782 1.0O 14.00 O
ATOM 5477 O HOH W 6 11.956 29.794 31.575 1.00 15.66 O
ATOM 5480 O HOH W 7 36.742 23.674 17.265 1.00 14.06 O
ATOM 5483 O HOH W 8 26.462 19.745 37.226 1.00 12.03 O
ATOM 5486 O HOH W 9 23.101 0.721 12.656 1.00 12.19 O
ATOM 5489 O HOH W 10 20.065 -2.650 26.156 1.00 20.32 O
ATOM 5492 O HOH W 11 18.435 36.223 15.049 1.00 20.55 O
ATOM 5495 O HOH W 12 18.961 -14.287 31.415 1.00 12.28 O
ATOM 5498 O HOH W 13 13.655 -3.630 28.503 1.00 11.25 O
ATOM 5501 O HOH W 14 6.772 28.494 24.564 1.00 16.02 O
ATOM 5504 O HOH W 15 25.827 -0.949 23.096 1.00 13.13 O
ATOM 5507 O HOH W 16 10.548 23.630 17.206 1.00 15.05 O
ATOM 5510 O HOH W 17 21.366 -0.008 27.896 1.00 14.00 O
ATOM 5513 O HOH W 18 6.571 29.390 22.100 1.00 18.38 O
ATOM 5516 O HOH W 19 25.418 4.779 24.010 1.00 11.22 O
ATOM 5519 O HOH W 20 15.446 15.813 32.417 1.00 13.39 O
ATOM 5522 O HOH W 21 5.625 22.360 17.718 1.00 14.91 O
ATOM 5525 O HOH W 22 27.953 5.617 25.060 1.00 12.69 O
ATOM 5528 O HOH W 23 13.200 17.441 16.128 1.00 12.98 O
ATOM 5531 O HOH W 24 42.359 19.143 18.719 1.00 14.71 O
ATOM 5534 O HOH W 25 24.537 -2.025 19.216 1.00 12.97 O
ATOM 5537 O HOH W 26 27.926 25.732 6.249 1.00 17.25 O
ATOM 5540 O HOH W 27 39.025 23.474 22.653 1.00 12.82 O
ATOM 5543 O HOH W 28 23.815 15.465 37.744 1.00 13.10 O
ATOM 5546 O HOH W 29 18.367 -9.817 33.092 1.00 17.61 O
ATOM 5549 O HOH W 30 20.380 12.554 15.652 1.00 10.66 O
ATOM 5552 O HOH W 31 18.651 1.596 26.271 1.00 14.85 O
ATOM 5555 O HOH W 32 35.209 6.007 10.838 1.00 15.93 O
ATOM 5558 O HOH W 33 18.465 24.874 35.632 1.00 11.70 O
ATOM 5561 O HOH W 34 20.815 27.470 36.539 1.00 14.90 O
ATOM 5564 O HOH W 35 20.733 10.911 9.565 1.00 14.64 O
ATOM 5567 O HOH W 36 4.788 27.744 28.587 1.00 16.40 O
ATOM 5570 O HOH W 37 8.972 17.007 35.207 1.00 15.88 O
ATOM 5573 O HOH W 38 33.433 11.882 27.279 1.00 15.71 O
ATOM 5576 O HOH W 39 11.974 0.247 27.662 1.00 14.69 O
ATOM 5579 O HOH W 40 11.026 22.081 14.883 1.00 14.23 O
ATOM 5582 O HOH W 41 26.884 -0.716 26.776 1.00 14.35 O
ATOM 5585 O HOH W 42 41.266 13.179 18.993 1.00 17.71 O
ATOM 5588 O HOH W 43 27.981 -2.861 17.044 1.00 20.05 O
ATOM 5591 O HOH W 44 2.212 -4.670 21.196 1.00 17.41 O
ATOM 5594 O HOH W 45 5.416 16.195 31.844 1.00 15.02 O
ATOM 5597 O HOH W 46 20.229 32.354 26.988 1.00 15.42 O
ATOM 5600 O HOH W 47 27.214 14.437 31.277 1.00 10.24 O
ATOM 5603 O HOH W 48 24.332 32.917 12.832 1.00 16.80 O
ATOM 5606 O HOH W 49 9.986 5.426 33.075 1.00 16.06 O
ATOM 5609 O HOH W 50 21.134 30.372 36.728 1.00 15.50 O
ATOM 5612 O HOH W 51 4.815 20.991 24.941 1.00 17.09 O
ATOM 5615 O HOH W 52 39.195 8.284 21.866 1.00 17.72 O
ATOM 5618 O HOH W 53 24.661 0.260 25.378 1.00 13.02 O
ATOM 5621 O HOH W 54 6.599 11.219 19.732 1.00 15.01 O
ATOM 5624 O HOH W 55 -1.402 -3.742 22.540 1.00 17.94 O
ATOM 5627 O HOH W 56 23.967 19.287 36.011 1.00 12.16 O
ATOM 5630 O HOH W 57 32.403 10.495 30.395 1.00 18.72 O
ATOM 5633 O HOH W 58 30.411 20.433 3.925 1.00 19.29 O
ATOM 5636 O HOH W 59 14.110 5.986 23.754 1.00 21.44 O
ATOM 5639 O HOH W 60 9.502 31.255 31.238 1.00 19.33 O
ATOM 5642 O HOH W 61 17.881 7.531 29.614 1.00 18.16 O
ATOM 5645 O HOH W 62 35.920 21.100 27.416 1.00 18.14 O
ATOM 5648 O HOH W 63 21.184 17.585 43.689 1.00 19.63 O
ATOM 5651 O HOH W 64 11.422 6.357 17.386 1.00 17.47 O
ATOM 5654 O HOH W 65 7.568 24.486 1.717 1.00 26.99 O
ATOM 5657 O HOH W 66 11.835 23.396 12.551 1.00 17.33 O
ATOM 5660 O HOH W 67 15.674 -0.267 13.102 1.00 28.14 O
ATOM 5663 O HOH W 68 35.246 4.205 18.695 1.00 18.92 O
ATOM 5666 O HOH W 69 12.071 7.219 35.891 1.00 17.95 O
ATOM 5669 O HOH W 70 33.151 1.122 14.747 1.00 19.80 O
ATOM 5672 O HOH W 71 22.406 17.015 36.075 1.00 12.42 O
ATOM 5675 O HOH W 72 20.744 5.444 32.336 1.00 24.35 O
ATOM 5678 O HOH W 73 20.988 -0.601 11.337 1.00 17.02 O
ATOM 5681 O HOH W 74 32.168 21.857 32.986 1.00 16.30 O
ATOM 5684 O HOH W 75 28.340 34.388 18.531 1.00 14.67 O
ATOM 5687 O HOH W 76 27.395 34.930 22.269 1.00 15.72 O
ATOM 5690 O HOH W 77 -2.881 1.257 27.203 1.00 24.36 O
ATOM 5693 O HOH W 78 1.320 22.974 26.514 1.00 16.10 O
ATOM 5696 O HOH W 79 20.014 2.049 4.590 1.00 18.49 O
ATOM 5699 O HOH W 80 20.131 -10.521 22.803 1.00 16.67 O
ATOM 5702 O HOH W 81 2.801 -12.938 26.738 1.00 21.33 O
ATOM 5705 O HOH W 82 13.524 14.422 42.122 1.00 22.70 O
ATOM 5708 O HOH W 83 41.288 13.787 8.384 1.00 21.34 O
ATOM 5711 O HOH W 84 33.383 31.044 25.382 1.00 20.83 O
ATOM 5714 O HOH W 85 39.402 29.928 19.487 1.00 19.25 O
ATOM 5717 O HOH W 86 14.181 -0.702 28.733 1.00 20.17 O
ATOM 5720 O HOH W 87 11.217 5.903 27.361 1.00 18.74 O
ATOM 5723 O HOH W 88 28.627 31.304 33.345 1.00 18.56 O
ATOM 5726 O HOH W 89 25.546 35.322 19.001 1.00 21.03 O
ATOM 5729 O HOH W 90 17.693 -0.865 33.818 1.00 23.45 O
ATOM 5732 O HOH W 91 16.853 2.781 26.050 1.00 20.34 O
ATOM 5735 O HOH W 92 34.612 21.168 14.066 1.00 15.33 O
ATOM 5738 O HOH W 93 19.619 19.119 0.936 1.00 29.35 O
ATOM 5741 O HOH W 94 20.721 21.727 42.621 1.00 20.03 O
ATOM 5744 O HOH W 95 17.040 19.477 42.629 1.00 20.78 O
ATOM 5747 O HOH W 96 20.111 -0.122 24.735 1.00 19.14 O
ATOM 5750 O HOH W 97 3.609 25.498 17.596 1.00 22.36 O
ATOM 5753 O HOH W 98 22.201 34.610 13.464 1.00 19.68 O
ATOM 5756 O HOH W 99 1.306 27.285 34.611 1.00 28.89 O
ATOM 5759 O HOH W 100 1.618 26.901 31.789 1.00 16.56 O
ATOM 5762 O HOH W 101 34.765 7.143 28.884 1.00 25.03 O
ATOM 5765 O HOH W 102 39.459 5.374 23.644 1.00 21.05 O
ATOM 5768 O HOH W 103 7.666 6.005 10.390 1.00 23.68 O
ATOM 5771 O HOH W 104 25.629 6.850 39.327 1.00 25.93 O
ATOM 5774 O HOH W 105 4.516 10.592 22.714 1.00 16.32 O
ATOM 5777 O HOH W 106 23.065 -8.147 22.078 1.00 22.91 O
ATOM 5780 O HOH W 107 15.215 5.229 8.027 1.00 18.64 O
ATOM 5783 O HOH W 108 9.120 -7.084 18.432 1.00 24.86 O
ATOM 5786 O HOH W 109 9.059 32.376 26.670 1.00 22.20 O
ATOM 5789 O HOH W 110 28.414 12.755 0.995 1.00 20.29 O
ATOM 5792 O HOH W 111 14.310 19.153 -3.544 1.00 25.42 O
ATOM 5795 O HOH W 112 18.007 -11.145 20.744 1.00 25.31 O
ATOM 5798 O HOH W 113 38.102 21.625 11.695 1.00 21.89 O
ATOM 5801 O HOH W 114 6.120 13.736 30.142 1.00 24.46 O
ATOM 5804 O HOH W 115 15.906 -18.386 31.627 1.00 22.15 O
ATOM 5807 O HOH W 116 22.389 33.907 19.142 1.00 22.92 O
ATOM 5810 O HOH W 117 32.200 35.724 21.334 1.00 26.32 O
ATOM 5813 O HOH W 118 2.190 17.510 6.678 1.00 25.22 O
ATOM 5816 O HOH W 119 1.118 4.704 29.359 1.00 25.72 O
ATOM 5819 O HOH W 120 9.611 1.556 17.312 1.00 23.94 O
ATOM 5822 O HOH W 121 3.629 23.370 16.136 1.00 22.93 O
ATOM 5825 O HOH W 122 32.907 25.232 8.564 1.00 22.34 O
ATOM 5828 O HOH W 123 -1.806 -9.230 29.885 1.00 26.14 O
ATOM 5831 O HOH W 124 32.230 21.567 30.291 1.00 23.29 O
ATOM 5834 O HOH W 125 37.450 14.678 29.329 1.00 25.24 O
ATOM 5837 O HOH W 126 15.339 36.760 18.883 1.00 20.61 O
ATOM 5840 O HOH W 127 10.235 7.567 31.063 1.00 21.51 O
ATOM 5843 O HOH W 128 24.897 37.442 19.549 1.00 24.86 O
ATOM 5846 O HOH W 129 17.030 -13.244 22.390 1.00 21.48 O
ATOM 5849 O HOH W 130 9.040 8.412 14.673 1.00 27.72 O
ATOM 5852 O HOH W 131 14.720 31.661 34.320 1.00 22.71 O
ATOM 5855 O HOH W 132 19.535 8.925 0.482 1.00 21.18 O
ATOM 5858 O HOH W 133 12.077 0.962 18.542 1.00 22.23 O
ATOM 5861 O HOH W 134 3.441 12.279 24.403 1.00 21.97 O
ATOM 5864 O HOH W 135 13.235 21.344 -4.722 1.00 25.46 O
ATOM 5867 O HOH W 136 4.989 14.655 27.582 1.00 28.75 O
ATOM 5870 O HOH W 137 -0.388 24.768 31.623 1.00 23.62 O
ATOM 5873 O HOH W 138 9.733 10.653 39.989 1.00 28.29 O
ATOM 5876 O HOH W 139 5.022 2.800 18.295 1.00 34.14 O
ATOM 5879 O HOH W 140 26.430 -3.864 19.091 1.00 26.57 O
ATOM 5882 O HOH W 141 33.127 12.459 35.197 1.00 24.55 O
ATOM 5885 O HOH W 142 4.529 14.653 24.602 1.00 27.79 O
ATOM 5888 O HOH W 143 34.889 3.006 29.679 1.00 26.45 O
ATOM 5891 O HOH W 144 26.472 27.781 5.265 1.00 24.30 O
ATOM 5894 O HOH W 145 9.844 1.973 10.352 1.00 30.48 O
ATOM 5897 O HOH W 146 23.113 35.988 15.667 1.00 24.26 O
ATOM 5900 O HOH W 147 3.506 18.934 26.329 1.00 23.36 O
ATOM 5903 O HOH W 148 41.932 12.669 10.942 1.00 26.60 O
ATOM 5906 O HOH W 149 40.619 12.671 22.354 1.00 26.08 O
ATOM 5909 O HOH W 150 33.062 38.217 15.479 1.00 37.76 O
ATOM 5912 O HOH W 151 3.554 31.071 10.635 1.00 26.96 O
ATOM 5915 O HOH W 152 14.084 8.928 41.767 1.00 28.97 O
ATOM 5918 O HOH W 153 29.827 1.222 9.591 1.00 30.85 O
ATOM 5921 O HOH W 154 23.088 -1.722 26.918 1.00 27.80 O
ATOM 5924 O HOH W 155 8.435 8.580 36.298 1.00 27.72 O
ATOM 5927 O HOH W 156 42.926 15.621 8.285 1.00 29.85 O
ATOM 5930 O HOH W 157 6.654 11.279 36.797 1.00 28.44 O
ATOM 5933 O HOH W 158 15.300 6.642 27.237 1.00 23.08 O
ATOM 5936 O HOH W 159 14.085 -11.817 20.799 1.00 27.86 O
ATOM 5939 O HOH W 160 -1.521 -6.774 36.408 1.00 31.93 O
ATOM 5942 O HOH W 161 15.519 1.708 31.201 1.00 27.02 O
ATOM 5945 O HOH W 162 0.621 -5.366 35.349 1.00 28.46 O
ATOM 5948 O HOH W 163 18.036 -12.751 33.648 1.00 22.09 O
ATOM 5951 O HOH W 164 32.843 18.669 30.344 1.00 28.48 O
ATOM 5954 O HOH W 165 27.765 11.874 38.295 1.00 18.10 O
ATOM 5957 O HOH W 166 1.781 17.606 13.084 1.00 28.85 O
ATOM 5960 O HOH W 167 20.211 0.158 6.249 1.00 29.98 O
ATOM 5963 O HOH W 168 2.759 19.112 32.488 1.00 24.07 O
ATOM 5966 O HOH W 169 33.968 18.793 32.524 1.00 23.54 O
ATOM 5969 O HOH W 170 -1.571 -13.592 26.165 1.00 34.45 O
ATOM 5972 O HOH W 171 39.370 28.627 17.071 1.00 26.29 O
ATOM 5975 O HOH W 172 17.376 32.794 35.436 1.00 23.98 O
ATOM 5978 O HOH W 173 9.391 6.761 35.029 1.00 21.74 O
ATOM 5981 O HOH W 174 16.352 11.687 43.877 1.00 31.51 O
ATOM 5984 O HOH W 175 36.018 4.292 25.853 1.00 21.19 O
ATOM 5987 O HOH W 176 24.899 -2.518 10.289 1.00 21.66 O
ATOM 5990 O HOH W 177 -1.286 2.934 25.647 1.00 31.88 O
ATOM 5993 O HOH W 178 13.449 -16.540 28.665 1.00 26.26 O
ATOM 5996 O HOH W 179 13.301 -0.613 16.357 1.00 27.05 O
ATOM 5999 O HOH W 180 24.842 17.585 44.930 1.00 26.85 O
ATOM 6002 O HOH W 181 5.856 18.874 39.008 1.00 29.19 O
ATOM 6005 O HOH W 182 -1.630 2.543 31.697 1.00 33.70 O
ATOM 6008 O HOH W 183 38.130 17.164 1.491 1.00 33.90 O
ATOM 6011 O HOH W 184 38.533 33.710 21.252 1.00 23.89 O
ATOM 6014 O HOH W 185 8.687 18.331 1.042 1.00 28.46 O
ATOM 6017 O HOH W 186 13.162 5.211 37.558 1.00 29.88 O
ATOM 6020 O HOH W 187 13.148 -16.170 33.001 1.00 24.01 O
ATOM 6023 O HOH W 188 17.877 11.059 1.344 1.00 30.31 O
ATOM 6026 O HOH W 189 1.036 -11.099 25.828 1.00 27.54 O
ATOM 6029 O HOH W 190 19.608 24.676 5.693 1.00 30.78 O
ATOM 6032 O HOH W 191 19.946 19.409 42.111 1.00 26.14 O
ATOM 6035 O HOH W 192 3.476 10.629 29.248 1.00 33.62 O
ATOM 6038 O HOH W 193 30.257 27.659 31.979 1.00 37.42 O
ATOM 6041 O HOH W 194 16.442 32.431 6.611 1.00 24.66 O
ATOM 6044 O HOH W 195 34.073 12.318 2.203 1.00 35.07 O
ATOM 6047 O HOH W 196 4.395 17.038 28.248 1.00 26.36 O
ATOM 6050 O HOH W 197 33.318 3.825 31.828 1.00 23.35 O
ATOM 6053 O HOH W 198 18.983 33.274 37.816 1.00 19.94 O
ATOM 6056 O HOH W 199 13.726 12.394 40.361 1.00 26.01 O
ATOM 6059 O HOH W 200 12.010 7.108 2.281 1.00 28.49 O
ATOM 6062 O HOH W 201 17.870 4.803 31.837 1.00 28.97 O
ATOM 6065 O HOH W 202 27.323 19.119 43.497 1.00 31.89 O
ATOM 6068 O HOH W 203 24.085 33.024 8.818 1.00 27.59 O
ATOM 6071 O HOH W 204 19.302 -7.180 37.095 1.00 25.01 O
ATOM 6074 O HOH W 205 34.921 3.097 15.744 1.00 35.90 O
ATOM 6077 O HOH W 206 22.046 36.365 19.883 1.00 33.71 O
ATOM 6080 O HOH W 207 4.178 27.080 39.663 1.00 28.68 O
ATOM 6083 O HOH W 208 21.450 25.719 2.335 1.00 29.50 O
ATOM 6086 O HOH W 209 7.625 37.543 22.457 1.00 27.39 O
ATOM 6089 O HOH W 210 27.905 0.363 30.805 1.00 27.13 O
ATOM 6092 O HOH W 211 29.963 26.817 34.574 1.00 28.33 O
ATOM 6095 O HOH W 212 37.812 29.413 15.021 1.00 35.13 O
ATOM 6098 O HOH W 213 31.600 5.299 33.905 1.00 30.36 O
ATOM 6101 O HOH W 214 0.934 2.893 30.953 1.00 26.27 O
ATOM 6104 O HOH W 215 15.151 -19.091 27.503 1.00 36.44 O
ATOM 6107 O HOH W 216 31.891 29.580 32.140 1.00 23.31 O
ATOM 6110 O HOH W 217 13.828 -7.788 38.638 1.00 33.17 O
ATOM 6113 O HOH W 218 37.026 8.221 8.178 1.00 43.15 O
ATOM 6116 O HOH W 219 12.026 -5.374 16.938 1.00 29.86 O
ATOM 6119 O HOH W 220 -1.767 -3.163 19.781 1.00 23.61 O
ATOM 6122 O HOH W 221 5.748 3.990 37.161 1.00 34.03 O
ATOM 6125 O HOH W 222 15.126 10.026 2.394 1.00 29.52 O
ATOM 6128 O HOH W 223 28.930 25.732 2.063 1.00 32.92 O
ATOM 6131 O HOH W 224 17.834 38.165 18.660 1.00 32.25 O
ATOM 6134 O HOH W 225 15.576 -9.633 19.956 1.00 29.35 O
ATOM 6137 O HOH W 226 21.532 33.500 36.344 1.00 30.91 O
ATOM 6140 O HOH W 227 37.166 25.308 14.969 1.00 30.80 O
ATOM 6143 O HOH W 228 4.201 13.978 20.632 1.00 29.14 O
ATOM 6146 O HOH W 229 -8.921 0.073 20.951 1.00 29.35 O
ATOM 6149 O HOH W 230 30.930 14.280 0.673 1.00 42.54 O
ATOM 6152 O HOH W 231 0.993 -10.363 23.294 1.00 35.64 O
ATOM 6155 O HOH W 232 19.283 -9.456 35.875 1.00 21.72 O
ATOM 6158 O HOH W 233 29.715 33.139 9.438 1.00 28.66 O
ATOM 6161 O HOH W 234 2.904 -7.322 21.953 1.00 29.37 O
ATOM 6164 O HOH W 235 -0.395 23.877 34.029 1.00 37.81 O
ATOM 6167 O HOH W 236 15.054 -3.907 38.561 1.00 26.91 O
ATOM 6170 O HOH W 237 25.729 34.682 11.457 1.00 29.23 O
ATOM 6173 O HOH W 238 9.385 33.323 24.057 1.00 36.55 O
ATOM 6176 O HOH W 239 24.093 -5.021 21.077 1.00 26.10 O
ATOM 6179 O HOH W 240 34.767 17.185 37.911 1.00 29.03 O
ATOM 6182 O HOH W 241 18.069 25.299 24.326 1.00 23.95 O
ATOM 6185 O HOH W 242 25.539 23.840 -0.133 1.00 27.32 O
ATOM 6188 O HOH W 243 -8.581 -0.882 24.380 1.0O 32.46 O
ATOM 6191 O HOH W 244 37.140 34.955 20.025 1.00 39.20 O
ATOM 6194 O HOH W 245 25.828 -6.464 17.951 1.0O 35.90 O
ATOM 6197 O HOH W 246 20.526 5.042 2.568 1.00 23.17 O
ATOM 6200 O HOH W 247 16.909 37.789 30.355 1.00 24.49 O
ATOM 6203 O HOH W 248 4.170 -13.753 24.179 1.00 34.75 O
ATOM 6206 O HOH W 249 4.757 29.554 36.890 1.00 27.07 O
ATOM 6209 O HOH W 250 14.985 25.383 44.611 1.00 36.67 O
ATOM 6212 O HOH W 251 21.002 34.942 26.743 1.00 24.40 O
ATOM 6215 O HOH W 252 35.187 37.614 16.171 1.00 41.70 O
ATOM 6218 O HOH W 253 9.429 35.849 24.299 1.00 29.47 O
ATOM 6221 O HOH W 254 22.360 -8.508 14.886 1.00 39.42 O
ATOM 6224 O HOH W 255 27.125 28.229 2.829 1.00 36.93 O
ATOM 6227 O HOH W 256 7.686 9.225 33.089 1.00 35.16 O
ATOM 6230 O HOH W 257 4.744 8.641 8.479 1.00 31.36 O
ATOM 6233 O HOH W 258 43.322 15.064 19.229 1.00 34.65 O
ATOM 6236 O HOH W 259 12.158 34.202 31.572 1.00 22.62 O
ATOM 6239 O HOH W 260 40.415 22.262 16.091 1.00 26.05 O
ATOM 6242 O HOH W 261 7.689 33.643 34.608 1.00 27.52 O
ATOM 6245 O HOH W 262 -2.516 -11.500 29.608 1.00 27.56 O
ATOM 6248 O HOH W 263 23.197 30.603 38.577 1.00 30.81 O
ATOM 6251 O HOH W 264 1.669 -4.135 18.399 1.00 34.72 O
ATOM 6254 O HOH W 265 31.682 18.313 2.510 1.00 27.38 O
ATOM 6257 O HOH W 266 21.515 33.588 40.094 1.00 30.03 O
ATOM 6260 O HOH W 267 16.458 13.271 -0.901 1.00 38.54 O
ATOM 6263 O HOH W 268 40.177 32.128 16.843 1.00 41.26 O
ATOM 6266 O HOH W 269 12.143 -2.734 15.885 1.00 27.02 O
ATOM 6269 O HOH W 270 27.486 -3.196 12.318 1.00 30.88 O
ATOM 6272 O HOH W 271 15.668 6.307 39.384 1.00 31.07 O
ATOM 6275 O HOH W 272 7.819 6.715 30.569 1.00 22.48 O
ATOM 6278 O HOH W 273 29.983 17.529 41.917 1.00 33.57 O
ATOM 6281 O HOH W 274 2.674 6.648 20.688 1.00 34.77 O
ATOM 6284 O HOH W 275 16.983 2.502 33.738 1.00 29.85 O
ATOM 6287 O HOH W 276 18.800 36.320 34.162 1.00 30.58 O
ATOM 6290 O HOH W 277 12.363 24.605 -1.596 1.00 34.55 O
ATOM 6293 O HOH W 278 14.702 17.110 -5.593 1.00 27.29 O
ATOM 6296 O HOH W 279 40.591 12.389 6.204 1.00 33.96 O
ATOM 6299 O HOH W 280 31.608 16.687 1.057 1.00 38.88 O
ATOM 6302 O HOH W 281 23.897 -11.952 20.222 1.00 34.68 O
ATOM 6305 O HOH W 282 11.219 39.478 21.517 1.00 33.54 O
ATOM 6308 O HOH W 283 2.552 16.703 24.563 1.00 35.86 O
ATOM 6311 O HOH W 284 27.258 9.495 42.694 1.00 30.97 O
ATOM 6314 O HOH W 285 5.535 8.881 16.549 1.00 28.65 O
ATOM 6317 O HOH W 286 2.189 24.192 36.099 1.00 31.47 O
ATOM 6320 O HOH W 287 19.058 -1.798 12.329 1.00 34.23 O
ATOM 6323 O HOH W 288 10.635 34.933 33.408 1.00 30.86 O
ATOM 6326 O HOH W 289 4.333 -0.576 36.893 1.00 44.65 O
ATOM 6329 O HOH W 290 25.069 21.389 -1.195 1.00 37.85 O
ATOM 6332 O HOH W 291 28.073 7.826 39.103 1.00 28.63 O
ATOM 6335 O HOH W 292 14.225 35.260 33.101 1.00 43.65 O
ATOM 6338 O HOH W 293 18.965 -2.916 15.137 1.00 38.32 O
ATOM 6341 O HOH W 294 40.370 19.000 13.716 1.00 33.50 O
ATOM 6344 O HOH W 295 6.261 32.033 33.639 1.00 30.04 O
ATOM 6347 O HOH W 296 13.696 37.943 17.160 1.00 36.07 O
ATOM 6350 O HOH W 297 2.518 21.734 35.950 1.00 40.41 O
ATOM 6353 O HOH W 298 31.821 26.389 38.109 1.00 33.84 O
ATOM 6356 O HOH W 299 -1.406 2.015 20.824 1.00 32.14 O
ATOM 6359 O HOH W 300 27.841 5.928 34.623 1.00 31.37 O
ATOM 6362 O HOH W 301 33.128 25.346 29.949 1.00 26.11 O
ATOM 6365 O HOH W 302 16.952 35.715 12.956 1.00 35.08 O
ATOM 6368 O HOH W 303 19.607 39.276 19.928 1.00 43.31 O
ATOM 6371 O HOH W 304 31.667 24.286 33.803 1.00 31.06 O
ATOM 6374 O HOH W 305 9.682 34.631 35.657 1.00 36.70 O
ATOM 6377 O HOH W 306 24.913 37.958 16.991 1.00 33.31 O
ATOM 6380 O HOH W 307 27.526 -1.443 8.577 1.00 31.08 O
ATOM 6383 O HOH W 308 34.923 14.237 35.665 1.00 33.29 O
ATOM 6386 O HOH W 309 23.480 3.819 33.037 1.00 28.70 O
ATOM 6389 O HOH W 310 39.917 30.468 13.351 1.00 43.99 O
ATOM 6392 O HOH W 311 20.005 30.742 39.713 1.00 31.34 O
ATOM 6395 O HOH W 312 1.762 19.900 10.728 1.00 33.53 O
ATOM 6398 O HOH W 313 21.282 35.887 11.600 1.00 34.66 O
ATOM 6401 O HOH W 314 22.512 -2.583 9.740 1.00 30.42 O
ATOM 6404 O HOH W 315 19.079 3.993 34.105 1.00 40.61 O
ATOM 6407 O HOH W 316 2.068 20.663 16.198 1.00 29.05 O
ATOM 6410 O HOH W 317 2.691 6.046 36.126 1.00 41.50 O
ATOM 6413 O HOH W 318 34.645 5.648 8.339 1.00 37.23 O
ATOM 6416 O HOH W 319 23.607 9.100 43.132 1.00 28.98 O
ATOM 6419 O HOH W 320 32.041 25.470 4.056 1.00 37.21 O
ATOM 6422 O HOH W 321 20.362 8.689 26.048 1.00 25.83 O
ATOM 6425 O HOH W 322 11.708 6.948 24.652 1.00 11.83 O
ATOM 6428 O HOH W 323 27.069 1.261 5.299 1.00 22.09 O
ATOM 6431 O HOH W 324 23.654 25.543 41.612 1.00 22.43 O
ATOM 6434 O HOH W 325 23.776 33.886 17.441 1.00 26.34 O
ATOM 6437 O HOH W 326 34.498 18.045 27.924 1.00 26.83 O
ATOM 6440 O HOH W 327 34.129 9.041 28.001 1.00 29.40 O
ATOM 6443 O HOH W 328 22.398 -4.833 18.306 1.00 31.97 O
ATOM 6446 O HOH W 329 32.650 36.061 13.569 1.00 32.16 O
ATOM 6449 O HOH W 330 18.875 6.699 27.476 1.00 31.00 O
ATOM 6452 O HOH W 331 43.627 18.936 5.210 1.00 33.15 O
ATOM 6455 O HOH W 332 13.390 23.630 -3.991 1.00 34.31 O
ATOM 6458 O HOH W 333 -0.102 6.438 34.964 1.00 48.55 O
ATOM 6461 O HOH W 334 -0.118 6.687 37.269 1.00 35.34 O
ATOM 6464 O HOH W 335 37.771 7.069 11.352 1.00 32.60 O
ATOM 6467 O HOH W 336 31.257 24.829 41.652 1.00 34.05 O
ATOM 6470 O HOH W 337 10.129 21.939 40.735 1.00 34.24 O
ATOM 6473 O HOH W 338 6.286 34.026 36.723 1.00 34.35 O
ATOM 6476 O HOH W 339 10.691 33.573 28.674 1.00 35.22 O
ATOM 6479 O HOH W 340 12.399 2.285 25.575 1.00 35.31 O
ATOM 6482 O HOH W 341 34.307 9.058 2.642 1.00 42.37 O
ATOM 6485 O HOH W 342 15.597 2.822 28.675 1.00 34.26 O
ATOM 6488 O HOH W 343 11.007 37.789 24.517 1.00 39.01 O
ATOM 6491 O HOH W 344 6.436 -13.362 22.903 1.00 41.47 O
ATOM 6494 O HOH W 345 19.680 17.126 45.857 1.00 37.81 O
ATOM 6497 O HOH W 346 10.533 36.113 27.412 1.00 34.50 O
ATOM 6500 O HOH W 347 41.809 19.887 16.869 1.00 37.61 O
ATOM 6503 O HOH W 348 21.611 15.053 -0.998 1.00 45.55 O
ATOM 6506 O HOH W 349 22.337 -9.031 17.861 1.00 49.31 O
ATOM 6509 O HOH W 350 9.303 25.984 -1.560 1.00 39.69 O
ATOM 6512 O HOH W 351 13.153 3.923 27.389 1.00 35.74 O
ATOM 6515 O HOH W 352 20.365 4.572 37.533 1.00 43.93 O
ATOM 6518 O HOH W 353 -2.246 27.322 10.724 1.00 42.74 O
ATOM 6521 O HOH W 354 9.435 33.000 4.908 1.00 38.59 O
ATOM 6524 O HOH W 355 15.473 17.843 44.371 1.00 40.00 O
ATOM 6527 O HOH W 356 13.009 31.258 32.197 1.00 21.10 O
ATOM 6530 O HOH W 357 36.838 8.242 3.607 1.00 35.04 O
ATOM 6533 O HOH W 358 30.674 -0.077 10.899 1.00 34.69 O
ATOM 6536 O HOH W 359 31.146 37.498 19.980 1.00 36.95 O
ATOM 6539 O HOH W 360 16.880 -0.664 8.461 1.00 39.07 O
ATOM 6542 O HOH W 361 40.707 6.845 20.023 1.00 32.40 O
ATOM 6545 O HOH W 362 19.502 25.524 0.606 1.00 41.49 O
ATOM 6548 O HOH W 363 27.574 22.139 44.653 1.00 52.17 O
ATOM 6551 O HOH W 364 11.308 11.015 41.537 1.00 41.08 O
ATOM 6554 O HOH W 365 9.385 -15.147 33.423 1.00 33.24 O
ATOM 6557 O HOH W 366 8.340 36.413 6.953 1.00 46.38 O
ATOM 6560 O HOH W 367 1.749 16.224 29.518 1.00 42.28 O
ATOM 6563 O HOH W 368 21.762 29.936 41.718 1.00 39.52 O
ATOM 6566 O HOH W 369 5.916 6.084 8.101 1.00 42.08 O
ATOM 6569 O HOH W 370 22.021 34.841 24.376 1.00 41.54 O
ATOM 6572 O HOH W 371 21.487 -18.393 21.594 1.00 38.90 O
ATOM 6575 O HOH W 372 39.073 5.237 9.752 1.00 40.75 O
ATOM 6578 O HOH W 373 23.013 -4.111 6.967 1.00 39.88 O
ATOM 6581 O HOH W 374 14.536 36.281 12.246 1.00 37.61 O
ATOM 6584 O HOH W 375 29.859 34.515 20.996 1.00 28.10 O
ATOM 6587 O HOH W 376 28.570 38.564 14.823 1.00 51.95 O
ATOM 6590 O HOH W 377 33.330 21.383 4.315 1.00 36.55 O
ATOM 6593 O HOH W 378 44.550 14.418 11.401 1.00 45.79 O
ATOM 6596 O HOH W 379 20.051 17.411 -1.528 1.00 37.86 O
ATOM 6599 O HOH W 380 0.588 25.706 15.094 1.00 42.46 O
ATOM 6602 O HOH W 381 4.339 -3.887 18.462 1.00 42.68 O
ATOM 6605 O HOH W 382 15.219 38.779 25.987 1.00 45.72 O
ATOM 6608 O HOH W 383 26.263 -1.807 0.657 1.00 35.43 O
ATOM 6611 O HOH W 384 43.222 8.889 13.058 1.00 39.12 O
ATOM 6614 O HOH W 385 3.804 15.072 37.146 1.00 35.83 O
ATOM 6617 O HOH W 386 13.685 22.152 44.161 1.00 46.34 O
ATOM 6620 O HOH W 387 39.745 6.714 14.451 1.00 43.87 O
ATOM 6623 O HOH W 388 4.160 10.246 14.729 1.00 40.70 O
ATOM 6626 O HOH W 389 8.951 3.749 5.381 1.00 35.43 O
ATOM 6629 O HOH W 390 12.861 -18.451 24.960 1.00 37.73 O
ATOM 6632 O HOH W 391 2.829 15.459 20.671 1.00 39.80 O
ATOM 6635 O HOH W 392 13.542 1.619 37.956 1.00 42.36 O
ATOM 6638 O HOH W 393 16.727 31.361 39.312 1.00 38.23 O
ATOM 6641 O HOH W 394 36.063 3.510 12.324 1.00 41.15 O
ATOM 6644 O HOH W 395 5.800 1.387 38.322 1.00 38.68 O
ATOM 6647 O HOH W 396 12.445 36.715 28.596 1.00 36.10 O
ATOM 6650 O HOH W 397 2.782 12.760 27.641 1.00 47.29 O
ATOM 6653 O HOH W 398 -1.700 -3.625 37.395 1.00 36.77 O
ATOM 6656 O HOH W 399 41.093 10.367 21.318 1.00 46.59 O
ATOM 6659 O HOH W 400 21.734 -5.069 9.760 1.00 48.11 O
ATOM 6662 O HOH W 401 14.290 3.253 24.475 1.00 36.49 O
ATOM 6665 O HOH W 402 22.729 2.974 -0.954 1.00 40.03 O
ATOM 6668 O HOH W 403 4.597 11.469 0.380 1.00 42.88 O
ATOM 6671 O HOH W 404 17.898 4.552 -0.927 1.00 39.85 O
序列表
<110>A.斯文森、H.德拉伯格、N.廷德贝克
<120>枯草杆菌酶变体
<130>10203.204-WO
<160>47
<170>PatentIn版本3.1
<210>1
<211>311
<212>PRT
<213>TY145枯草杆菌酶
<220>
<221>肽
<222>(1)..(311)
<223>
<400>1
Ala Val Pro Ser Thr Gln Thr Pro Trp Gly Ile Lys Ser Ile Tyr Asn
1 5 10 15
Asp Gln Ser Ile Thr Lys Thr Thr Gly Gly Ser Gly Ile Lys Val Ala
20 25 30
Val Leu Asp Thr Gly Val Tyr Thr Ser His Leu Asp Leu Ala Gly Ser
35 40 45
Ala Glu Gln Cys Lys Asp Phe Thr Gln Ser Asn Pro Leu Val Asp Gly
50 55 60
Ser Cys Thr Asp Arg Gln Gly His Gly Thr His Val Ala Gly Thr Val
65 70 75 80
Leu Ala His Gly Gly Ser Asn Gly Gln Gly Val Tyr Gly Val Ala Pro
85 90 95
Gln Ala Lys Leu Trp Ala Tyr Lys Val Leu Gly Asp Asn Gly Ser Gly
100 105 110
Tyr Ser Asp Asp Ile Ala Ala Ala Ile Arg His Val Ala Asp Glu Ala
115 120 125
Ser Arg Thr Gly Ser Lys Val Val Ile Asn Met Ser Leu Gly Ser Ser
130 135 140
Ala Lys Asp Ser Leu Ile Ala Ser Ala Val Asp Tyr Ala Tyr Gly Lys
145 150 155 160
Gly Val Leu Ile Val Ala Ala Ala Gly Asn Ser Gly Ser Gly Ser Asn
165 170 175
Thr Ile Gly Phe Pro Gly Gly Leu Val Asn Ala Val Ala Val Ala Ala
180 185 190
Leu Glu Asn Val Gln Gln Asn Gly Thr Tyr Arg Val Ala Asp Phe Ser
195 200 205
Ser Arg Gly Asn Pro Ala Thr Ala Gly Asp Tyr Ile Ile Gln Glu Arg
210 215 220
Asp Ile Glu Val Ser Ala Pro Gly Ala Ser Val Glu Ser Thr Trp Tyr
225 230 235 240
Thr Gly Gly Tyr Asn Thr Ile Ser Gly Thr Ser Met Ala Thr Pro His
245 250 255
Val Ala Gly Leu Ala Ala Lys Ile Trp Ser Ala Asn Thr Ser Leu Ser
260 265 270
His Ser Gln Leu Arg Thr Glu Leu Gln Asn Arg Ala Lys Val Tyr Asp
275 280 285
Ile Lys Gly Gly Ile Gly Ala Gly Thr Gly Asp Asp Tyr Ala Ser Gly
290 295 300
Phe Gly Tyr Pro Arg Val Lys
305 310
<210>2
<211>420
<212>PRT
<213>TA39枯草杆菌酶
<220>
<221>肽
<222>(1)..(420)
<223>
<400>2
Met Lys Arg Ser Gly Lys Ile Phe Thr Thr Ala Met Leu Ala Val Thr
1 5 10 15
Leu Met Met Pro Ala Met Gly Val Ser Ala Asn Glu Gly Asn Ala Ala
20 25 30
Ala Glu Gly Asn Glu Lys Phe Arg Val Leu Val Asp Ser Val Asp Gln
35 40 45
Lys Asn Leu Lys Asn Ala Lys Gln Gln Tyr Gly Val His Trp Asp Phe
50 55 60
Ala Gly Glu Gly Phe Thr Thr Asp Met Asn Glu Lys Gln Phe Asn Ala
65 70 75 80
Leu Lys Lys Asn Lys Asn Leu Thr Val Glu Lys Val Pro Glu Leu Glu
85 90 95
Ile Ala Thr Ala Thr Asp Lys Pro Glu Ala Leu Tyr Asn Ala Met Ala
100 105 110
Ala Ser Gln Ser Thr Pro Trp Gly Ile Lys Ala Ile Tyr Asn Asn Ser
115 120 125
Ser Ile Thr Gln Thr Ser Gly Gly Gly Gly Ile Asn Ile Ala Val Leu
130 135 140
Asp Thr Gly Val Asn Thr Asn His Pro Asp Leu Arg Asn Asn Val Glu
145 150 155 160
Gln Cys Lys Asp Phe Thr Val Gly Thr Thr Tyr Thr Asn Asn Ser Cys
165 170 175
Thr Asp Arg Gln Gly His Gly Thr His Val Ala Gly Ser Ala Leu Ala
180 185 190
Asp Gly Gly Thr Gly Asn Gly Val Tyr Gly Val Ala Pro Asp Ala Asp
195 200 205
Leu Trp Ala Tyr Lys Val Leu Gly Asp Asp Gly Ser Gly Tyr Ala Asp
210 215 220
Asp Ile Ala Ala Ala Ile Arg His Ala Gly Asp Gln Ala Thr Ala Leu
225 230 235 240
Asn Thr Lys Val Val Ile Asn Met Ser Leu Gly Ser Ser Gly Glu Ser
245 250 255
Ser Leu Ile Thr Asn Ala Val Asn Tyr Ser Tyr Asn Lys Gly Val Leu
260 265 270
Ile Ile Ala Ala Ala Gly Asn Ser Gly Pro Tyr Gln Gly Ser Ile Gly
275 280 285
Tyr Pro Gly Ala Leu Val Asn Ala Val Ala Val Ala Ala Leu Glu Asn
290 295 300
Lys Val Glu Asn Gly Thr Tyr Arg Val Ala Asp Phe Ser Ser Arg Gly
305 310 315 320
Tyr Ser Trp Thr Asp Gly Asp Tyr Ala Ile Gln Lys Gly Asp Val Glu
325 330 335
Ile Ser Ala Pro Gly Ala Ala Ile Tyr Ser Thr Trp Phe Asp Gly Gly
340 345 350
Tyr Ala Thr Ile Ser Gly Thr Ser Met Ala Ser Pro His Ala Ala Gly
355 360 365
Leu Ala Ala Lys Ile Trp Ala Gln Tyr Pro Ser Ala Ser Asn Val Asp
370 375 380
Val Arg Gly Glu Leu Gln Tyr Arg Ala Tyr Glu Asn Asp Ile Leu Ser
385 390 395 400
Gly Tyr Tyr Ala Gly Tyr Gly Asp Asp Phe Ala Ser Gly Phe Gly Phe
405 410 415
Ala Thr Val Gln
420
<210>3
<211>419
<212>PRT
<213>TA41枯草杆菌酶
<220>
<221>肽
<222>(1)..(419)
<223>
<400>3
Met Lys Arg Ser Gly Lys Ile Phe Thr Thr Ala Met Leu Ala Val Thr
1 5 10 15
Leu Met Met Pro Ala Ile Gly Val Ser Ala Asn Arg Gly Asn Ala Ala
20 25 30
Asp Gly Asn Glu Lys Phe Arg Val Leu Val Asp Ser Ala Asn Gln Asn
35 40 45
Asn Leu Lys Asn Val Lys Glu Gln Tyr Gly Val His Trp Asp Phe Ala
50 55 60
Gly Glu Gly Phe Thr Thr Asn Met Asn Glu Lys Gln Phe Asn Ala Leu
65 70 75 80
Gln Asn Asn Lys Asn Leu Thr Val Glu Lys Val Pro Glu Leu Glu Ile
85 90 95
Ala Thr Ala Thr Asn Lys Pro Glu Ala Leu Tyr Asn Ala Met Ala Ala
100 105 110
Ser Gln Ser Thr Pro Trp Gly lle Lys Ala Ile Tyr Asn Asn Ser Asn
115 120 125
Leu Thr Ser Thr Ser Gly Gly Ala Gly Ile Asn Ile Ala Val Leu Asp
130 135 140
Thr Gly Val Asn Thr Asn His Pro Asp Leu Ser Asn Asn Val Glu Gln
145 150 155 160
Cys Lys Asp Phe Thr Val Gly Thr Asn Phe Thr Asp Asn Ser Cys Thr
165 170 175
Asp Arg Gln Gly His Gly Thr His Val Ala Gly Ser Ala Leu Ala Asn
180 185 190
Gly Gly Thr Gly Ser Gly Val Tyr Gly Val Ala Pro Glu Ala Asp Leu
195 200 205
Trp Ala Tyr Lys Val Leu Gly Asp Asp Gly Ser Gly Tyr Ala Asp Asp
210 215 220
Ile Ala Glu Ala Ile Arg His Ala Gly Asp Gln Ala Thr Ala Leu Asn
225 230 235 240
Thr Lys Val Val Ile Asn Met Ser Leu Gly Ser Ser Gly Glu Ser Ser
245 250 255
Leu Ile Thr Asn Ala Val Asp Tyr Ala Tyr Asp Lys Gly Val Leu Ile
260 265 270
Ile Ala Ala Ala Gly Asn Ser Gly Pro Lys Pro Gly Ser Ile Gly Tyr
275 280 285
Pro Gly Ala Leu Val Asn Ala Val Ala Val Ala Ala Leu Glu Asn Thr
290 295 300
Ile Gln Asn Gly Thr Tyr Arg Val Ala Asp Phe Ser Ser Arg Gly His
305 310 315 320
Lys Arg Thr Ala Gly Asp Tyr Val Ile Gln Lys Gly Asp Val Glu Ile
325 330 335
Ser Ala Pro Gly Ala Ala Val Tyr Ser Thr Trp Phe Asp Gly Gly Tyr
340 345 350
Ala Thr Ile Ser Gly Thr Ser Met Ala Ser Pro His Ala Ala Gly Leu
355 360 365
Ala Ala Lys Ile Trp Ala Gln Ser Pro Ala Ala Ser Asn Val Asp Val
370 375 380
Arg Gly Glu Leu Gln Thr Arg Ala Ser Val Asn Asp Ile Leu Ser Gly
385 390 395 400
Asn Ser Ala Gly Ser Gly Asp Asp Ile Ala Ser Gly Phe Gly Phe Ala
405 410 415
Lys Val Gln
<210>4
<211>310
<212>PRT
<213>球形芽孢杆菌sphericase
<220>
<221>肽
<222>(1)..(310)
<223>
<400>4
Arg Ala Ser Gln Gln Ile Pro Trp Gly Ile Lys Ala Ile Tyr Asn Asn
1 5 10 15
Asp Thr Leu Thr Ser Thr Thr Gly Gly Ser Gly Ile Asn Ile Ala Val
20 25 30
Leu Asp Thr Gly Val Asn Thr Ser His Pro Asp Leu Val Asn Asn Val
35 40 45
Glu Gln Cys Lys Asp Phe Thr Gly Ala Thr Thr Pro Ile Asn Asn Ser
50 55 60
Cys Thr Asp Arg Asn Gly His Gly Thr His Val Ala Gly Thr Ala Leu
65 70 75 80
Ala Asp Gly Gly Ser Asp Gln Ala Gly Ile Tyr Gly Val Ala Pro Asp
85 90 95
Ala Asp Leu Trp Ala Tyr Lys Val Leu Leu Asp Ser Gly Ser Gly Tyr
l00 105 110
Ser Asp Asp Ile Ala Ala Ala Ile Arg His Ala Ala Asp Gln Ala Thr
115 120 125
Ala Thr Gly Thr Lys Thr Ile Ile Ser Met Ser Leu Gly Ser Ser Ala
130 135 140
Asn Asn Ser Leu Ile Ser Ser Ala Val Asn Tyr Ala Tyr Ser Lys Gly
145 150 155 160
Val Leu Ile Val Ala Ala Ala Gly Asn Ser Gly Tyr Ser Gln Gly Thr
165 170 175
Ile Gly Tyr Pro Gly Ala Leu Pro Asn Ala Ile Ala Val Ala Ala Leu
180 185 190
Glu Asn Val Gln Gln Asn Gly Thr Tyr Arg Val Ala Asp Tyr Ser Ser
195 200 205
Arg Gly Tyr Ile Ser Thr Ala Gly Asp Tyr Val Ile Gln Glu Gly Asp
210 215 220
Ile Glu Ile Ser Ala Pro Gly Ser Ser Val Tyr Ser Thr Trp Tyr Asn
225 230 235 240
Gly Gly Tyr Asn Thr Ile Ser Gly Thr Ser Met Ala Thr Pro His Val
245 250 255
Ser Gly Leu Ala Ala Lys Ile Trp Ala Glu Asn Pro Ser Leu Ser Asn
260 265 270
Thr Gln Leu Arg Ser Asn Leu Gln Glu Arg Ala Lys Ser Val Asp Ile
275 280 285
Lys Gly Gly Tyr Gly Ala Ala Ile Gly Asp Asp Tyr Ala Ser Gly Phe
290 295 300
Gly Phe Ala Arg Val Gln
305 310
<210>5
<211>275
<212>PRT
<213>淀粉芽孢杆菌
<220>
<221>肽
<222>(1)..(275)
<223>BPN′
<400>5
Ala Gln Ser Val Pro Tyr Gly Val Ser Gln Ile Lys Ala Pro Ala Leu
1 5 10 15
His Ser Gln Gly Tyr Thr Gly Ser Asn Val Lys Val Ala Val Ile Asp
20 25 30
Ser Gly Ile Asp Ser Ser His Pro Asp Leu Lys Val Ala Gly Gly Ala
35 40 45
Ser Met Val Pro Ser Glu Thr Asn Pro Phe Gln Asp Asn Asn Ser His
50 55 60
Gly Thr His Val Ala Gly Thr Val Ala Ala Leu Asn Asn Ser Ile Gly
65 70 75 80
Val Leu Gly Val Ala Pro Ser Ala Ser Leu Tyr Ala Val Lys Val Leu
85 90 95
Gly Ala Asp Gly Ser Gly Gln Tyr Ser Trp Ile Ile Asn Gly Ile Glu
100 105 110
Trp Ala Ile Ala Asn Asn Met Asp Val Ile Asn Met Ser Leu Gly Gly
115 120 125
Pro Ser Gly Ser Ala Ala Leu Lys Ala Ala Val Asp Lys Ala Val Ala
130 135 140
Ser Gly Val Val Val Val Ala Ala Ala Gly Asn Glu Gly Thr Ser Gly
145 150 155 160
Ser Ser Ser Thr Val Gly Tyr Pro Gly Lys Tyr Pro Ser Val Ile Ala
165 170 175
Val Gly Ala Val Asp Ser Ser Asn Gln Arg Ala Ser Phe Ser Ser Val
180 185 190
Gly Pro Glu Leu Asp Val Met Ala Pro Gly Val Ser Ile Gln Ser Thr
195 200 205
Leu Pro Gly Asn Lys Tyr Gly Ala Tyr Asn Gly Thr Ser Met Ala Ser
210 215 220
Pro His Val Ala Gly Ala Ala Ala Leu Ile Leu Ser Lys His Pro Asn
225 230 235 240
Trp Thr Asn Thr Gln Val Arg Ser Ser Leu Glu Asn Thr Thr Thr Lys
245 250 255
Leu Gly Asp Ser Phe Tyr Tyr Gly Lys Gly Leu Ile Asn Val Gln Ala
260 265 270
Ala Ala Gln
275
<210>6
<211>269
<212>PRT
<213>迟缓芽孢杆菌
<220>
<221>肽
<222>(1)..(269)
<223>Savinase
<400>6
Ala Gln Ser Val Pro Trp Gly Ile Ser Arg Val Gln Ala Pro Ala Ala
1 5 10 15
His Asn Arg Gly Leu Thr Gly Ser Gly Val Lys Val Ala Val Leu Asp
20 25 30
Thr Gly Ile Ser Thr His Pro Asp Leu Asn Ile Arg Gly Gly Ala Ser
35 40 45
Phe Val Pro Gly Glu Pro Ser Thr Gln Asp Gly Asn Gly His Gly Thr
50 55 60
His Val Ala Gly Thr Ile Ala Ala Leu Asn Asn Ser Ile Gly Val Leu
65 70 75 80
Gly Val Ala Pro Ser Ala Glu Leu Tyr Ala Val Lys Val Leu Gly Ala
85 90 95
Ser Gly Ser Gly Ser Val Ser Ser Ile Ala Gln Gly Leu Glu Trp Ala
100 105 110
Gly Asn Asn Gly Met His Val Ala Asn Leu Ser Leu Gly Ser Pro Ser
115 120 125
Pro Ser Ala Thr Leu Glu Gln Ala Val Asn Ser Ala Thr Ser Arg Gly
130 135 140
Val Leu Val Val Ala Ala Ser Gly Asn Ser Gly Ala Gly Ser Ile Ser
145 150 155 160
Tyr Pro Ala Arg Tyr Ala Asn Ala Met Ala Val Gly Ala Thr Asp Gln
165 170 175
Asn Asn Asn Arg Ala Ser Phe Ser Gln Tyr Gly Ala Gly Leu Asp Ile
180 185 190
Val Ala Pro Gly Val Asn Val Gln Ser Thr Tyr Pro Gly Ser Thr Tyr
195 200 205
Ala Ser Leu Asn Gly Thr Ser Met Ala Thr Pro His Val Ala Gly Ala
210 215 220
Ala Ala Leu Val Lys Gln Lys Asn Pro Ser Trp Ser Asn Val Gln Ile
225 230 235 240
Arg Asn His Leu Lys Asn Thr Ala Thr Ser Leu Gly Ser Thr Asn Leu
245 250 255
Tyr Gly Ser Gly Leu Val Asn Ala Glu Ala Ala Thr Arg
260 265
<210>7
<211>60
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(60)
<223>引物28-35-CN
<400>7
tagatctgga tgagtggawv yccctgtatc gaggacagcw rbttttacac cagaacctgt 60
<210>8
<211>18
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(18)
<223>引物28-35.NC
<400>8
tccactcatc cagatcta 18
<210>9
<211>45
<212>DNA
<213>人工的
<220>
<221>misc_feature
<222>(1)..(45)
<223>引物71-72-73-CN(I)
<400>
aatcgaattg tttaaagcag cwvyygwccc ggccacatgc gtgcc 45
<210>10
<211>45
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(45)
<223>引物71-72-73-CN(II)
<400>10
aatcgaattg tttaaagcaa gwvyygwccc ggccacatgc gtgcc 45
<210>11
<211>45
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(45)
<223>引物71-72-73-CN(III)
<400>11
aatcgaattg tttaaagcgc cwvyygwccc ggccacatgc gtgcc 45
<210>12
<211>18
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(18)
<223>引物71-72-73-NC
<400>12
gctttaaaca attcgatt 18
<210>13
<211>24
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(24)
<223>引物139
<400>13
gattaacgcg ttgccgcttc tgcg 24
<210>14
<211>39
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(39)
<223>引物175-CN(I)
<400>14
atcagtagct ccgactgcca ytgcgttcgc atagcgcgc 39
<210>15
<211>39
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(39)
<223>引物175-CN(II)
<400>15
atcagtagct ccgactgccg ctgcgttcgc atagcgcgc 39
<210>16
<211>18
<2l2>DNA
<213>人工的
<220>
<221>misc_feature
<222>(1)..(18)
<223>引物175-NC
<400>16
gcagtcggag ctactgat 18
<210>17
<211>39
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(39)
<223>引物224-CN
<400>17
cgcacctgca acatgaggcg hagccatcga tgtaccgtt 39
<210>18
<211>18
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(18)
<223>引物224-NC
<400>18
cctcatgttg caggtgcg 18
<210>19
<211>22
<212>DNA
<213>人工序列
<220>
<223>合成寡肽
<220>
<221>misc_feature
<222>(1)..(22)
<223>引物317-CN
<400>19
tggcgcaatc ggtaccatgg gg 22
<210>20
<211>936
<212>DNA
<213>TY145枯草杆菌酶DNA
<400>20
gcggtaccaa gtacacaaac cccttggggc ataaagtcaa tttataatga tcaatcaatt 60
acaaaaacaa ctggaggcag cggaattaag gtagctgttt tagatacagg ggtttataca 120
agccatttag atttagctgg ttctgccgag caatgcaagg attttaccca atctaatcct 180
ttagtagatg gttcatgcac cgatcgccaa gggcatggta cacatgttgc cggaactgta 240
ttggcgcatg gaggcagtaa tggacaaggc gtttacgggg tggctccgca agcgaaacta 300
tgggcatata aagtattagg agataacggc agcggatact ctgatgatat tgcagcagct 360
atcagacatg tagctgatga agcttcacgt acaggttcca aagtagtaat taatatgtcg 420
ctaggttcat ctgccaagga ttcattgatt gctagtgcag tagattatgc atatggaaaa 480
ggtgtattaa tcgttgctgc ggctggtaat agtgggtcag gcagcaatac aatcggcttt 540
cctggcgggc ttgtaaatgc agtggcagta gcggcattgg agaatgttca gcaaaatgga 600
acttatcgag tagctgattt ctcatctaga gggaatccgg caactgctgg agattatatc 660
attcaagagc gtgatattga agtttcagct ccgggagcaa gtgtagagtc tacatggtac 720
actggcggtt ataatacgat cagcggtaca tcaatggcta cacctcatgt agctgggtta 780
gctgctaaaa tctggtcagc gaatacttca ttaagtcata gccaactgcg cacagaattg 840
caaaatcgcg ctaaagtata tgatattaaa ggtggtatcg gagccggaac aggtgacgat 900
tatgcatcag ggttcggata tccaagagta aaataa 936
<210>21
<211>1143
<212>DNA
<213>迟缓芽孢杆菌,Savinase
<400>21
atgaagaaac cgttggggaa aattgtcgca agcaccgcac tactcatttc tgttgctttt 60
agttcatcga tcgcatcggc tgctgaagaa gcaaaagaaa aatatttaat tggctttaat 120
gagcaggaag ctgtcagtga gtttgtagaa caagtagagg caaatgacga ggtcgccatt 180
ctctctgagg aagaggaagt cgaaattgaa ttgcttcatg aatttgaaac gattcctgtt 240
ttatccgttg agttaagccc agaagatgtg gacgcgcttg aactcgatcc agcgatttct 300
tatattgaag aggatgcaga agtaacgaca atggcgcaat cggtaccatg gggaattagc 360
cgtgtgcaag ccccagctgc ccataaccgt ggattgacag gttctggtgt aaaagttgct 420
gtcctcgata cagggatatc cactcatcca gatctaaata ttcgtggtgg cgcaagcttt 480
gtaccagggg aaccgtcgac tcaagatggg aatgggcatg gcacgcatgt ggccgggacg 540
atcgctgctt taaacaattc gattggcgtt cttggcgtag cgccgagcgc tgagctatac 600
gctgttaaag tcctaggggc gagcggttca ggttcggtca gctcgattgc ccaaggattg 660
gaatgggcag ggaacaatgg catgcacgtt gctaatttga gtttaggaag cccttcgcca 720
agtgccacac tcgagcaagc tgttaatagc gcgacttcta gaggcgttct tgttgtagcg 780
gcatctggga attcaggtgc aggctcaatc agctatccgg cgcgctatgc gaacgcaatg 840
gcagtcggag ctactgatca aaacaacaac cgcgctagct tttcacagta tggcgcaggc 900
cttgacattg tcgcacccgg ggtaaacgtg cagagcacat acccaggttc aacatatgcc 960
agcttaaacg gtacatcgat ggctactcct catgttgcag gtgcggccgc ccttgttaaa 1020
caaaagaacc catcttggtc taatgtacaa attcgaaatc atctaaagaa tacggcaact 1080
agtttaggaa gcacgaactt gtatggaagc ggacttgtta acgcagaagc ggcaacgcgt 1140
taa 1143
<210>22
<211>12
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>22
Ser Ala Lys Asp Ser Leu Ile Ala Ser Ala Val Asp
1 5 10
<210>23
<211>12
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>23
Pro Ser Pro Ser Ala Thr Leu Glu Gln Ala Val Asn
1 5 10
<210>24
<211>18
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>24
Ala Gly Asn Ser Gly Ser Gly Ser Asn Thr Ile Gly Phe Pro Gly Gly
1 5 10 15
Leu Val
<210>25
<211>16
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>25
Ser Gly Asn Ser Gly Ala Gly Ser Ile Ser Tyr Pro Ala Arg Tyr Ala
1 5 10 15
<210>26
<211>16
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>26
Ala Ser Val Glu Ser Thr Trp Tyr Thr Gly Gly Tyr Asn Thr Ile Ser
1 5 10 15
<210>27
<211>16
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>27
Val Asn Val Gln Ser Thr Tyr Pro Gly Ser Thr Tyr Ala Ser Leu Asn
1 5 10 15
<210>28
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>28
Met Ser Leu Gly Ser Ser Gly
1 5
<210>29
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>29
Leu Ser Leu Gly Ser Pro Ser
1 5
<210>30
<211>12
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>30
Met Ser Leu Gly Ser Ser Gly Glu Ser Ser Leu Ile
1 5 10
<210>31
<211>12
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>31
Leu Ser Leu Gly Ser Pro Ser Pro Ser Ala Thr Leu
1 5 10
<210>32
<211>8
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>32
Asn Asn Ser Ser Ile Thr Gln Thr
1 5
<210>33
<211>8
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>33
Val Gln Ala Pro Ala Ala His Asn
1 5
<210>34
<211>8
<212>PRT
<213>人工序列
<220>
<223>Sayinase的高变区
<400>34
Thr Val Gly Thr Thr Tyr Thr Asn
1 5
<210>35
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>35
Val Pro Gly Glu Pro Ser Thr
1 5
<210>36
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>36
Ser Gly Glu Ser Ser Leu Ile
1 5
<210>37
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>37
Pro Ser Pro Ser Ala Thr Leu
1 5
<210>38
<211>9
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>38
Trp Phe Asp Gly Gly Tyr Ala Thr Ile
1 5
<210>39
<211>9
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>39
Tyr Pro Gly Ser Thr Tyr Ala Ser Leu
1 5
<210>40
<211>8
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>40
Thr Val Gly Thr Asn Phe Thr Asp
1 5
<210>41
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>41
Val Pro Gly Glu Pro Ser Thr
1 5
<210>42
<211>6
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>42
Asn Gly Gly Thr Gly Ser
1 5
<210>43
<211>6
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>43
Ala Leu Asn Asn Ser Ile
1 5
<210>44
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>44
Asp Asp Gly Ser Gly Tyr Ala
1 5
<210>45
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>45
Ala Ser Gly Ser Gly Ser Val
1 5
<210>46
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>46
Trp Ala Gln Ser Pro Ala Ala
l 5
<210>47
<211>7
<212>PRT
<213>人工序列
<220>
<223>Savinase的高变区
<400>47
Lys Gln Lys Asn Pro Ser Trp
1 5
<210>48
<211>6
<212>PRT
<213>人工序列
<220>
<223>离子结合位点
<400>48
Leu Asn Asn Ser Ile Gly
1 5
<210>49
<211>3
<212>PRT
<213>人工序列
<220>
<223>离子结合位点
<400>49
Gly Asp Ser
1
<210>50
<211>3
<212>PRT
<213>人工序列
<220>
<223>离子结合位点
<400>50
Asp Ser Thr
1
<210>51
<211>5
<212>PRT
<213>人工序列
<220>
<223>离子结合位点
<400>51
Gly Gly Ser Asn Gly
1 5
Claims (47)
1.与SEQ ID NO:1至少有63%同源性的TY145样枯草杆菌酶,其包含全部枯草菌素折叠和以下结构特征:
a)7条链的β片层,
b)6个α螺旋,
c)至少3个离子结合位点,
其中不存在BPN’样枯草杆菌酶的强离子结合位点,且TY145枯草杆菌酶、TA39来源的S39枯草杆菌酶、TA41来源的S41枯草杆菌酶和球形芽孢杆菌来源的球形酶除外。
2.权利要求1的枯草杆菌酶,其中所述3个离子结合位点在枯草杆菌酶三维结构中的位置通过与枯草杆菌酶3个活性位点氨基酸残基c-α原子,即丝氨酸、组氨酸和天冬氨酸,以及与紧随活性位点丝氨酸残基之后(紧随丝氨酸之后)的氨基酸残基的c-α原子的距离定义,其中:
a)弱离子结合位点与i)天冬氨酸c-α原子的距离为17.50-19.50_,与ii)组氨酸c-α原子的距离为21-23_,iii)丝氨酸c-α原子的距离为13.80-15.80_,与iv)紧靠丝氨酸c-α原子的距离为15.80-17.80_,
b)远离子结合位点与i)天冬氨酸c-α原子的距离为28.70-30.70_,与ii)组氨酸c-α原子的距离为28-30_,与iii)丝氨酸c-α原子的距离为20-22_,与iv)紧靠丝氨酸c-α原子的距离为19.50-21.50_,
c)近离子结合位点与i)天冬氨酸c-α原子的距离为27-29_,与ii)组氨酸c-α原子的距离为29.50-31.50_,与iii)丝氨酸c-α原子的距离为is21.40-23.40_,与iv)紧靠丝氨酸c-α原子的距离为22.50-24.50_,
3.根据权利要求2的枯草杆菌酶,其中3个离子结合位点的位置通过与SEQ ID NO:1的氨基酸残基D35、H72、S251和M252的c-α原子的距离定义,或通过与符合权利要求1的其他本发明枯草杆菌酶中等效的氨基酸残基的距离定义,其中:
a)弱离子结合位点与i)D35c-α原子的距离为18.55_,与ii)H72c-α原子的距离为21.98_,与iii)S251c-α原子的距离为14.71_,与iv)M252c-α原子的距离为16.75_,
b)远离子结合位点与i)D35c-α原子的距离为29.68_,与ii)H72c-α原子的距离为29.10_,与iii)S251c-α原子的距离为20.96_,与iv)M252c-α原子的距离为20.35_,
c)近离子结合位点与i)D35c-α原子的距离为28.04_,与ii)H72c-α原子的距离为30.43_,与iii)S251c-α原子的距离为22.28_,与iv)M252c-α原子的距离为23.58_,
其中上述距离的变化范围为±0.8_,优选±0.7_,更优选±0.6_,更优选±0.5_,更优选±0.4_,或最优选±0.3_。
4.产生亲本TY145样枯草杆菌酶变体的方法,其变体与亲本TY145样枯草杆菌酶相比至少具有一种改变的特性,该方法包括:
a)在TY145枯草杆菌酶三维结构上建立亲本TY145样枯草杆菌酶模型,以产生亲本TY145样枯草杆菌酶的三维结构;
b)将步骤a)中得到的三维结构与TY145枯草杆菌酶三维结构进行比较;
c)在步骤b)的比较基础上鉴定出亲本TY145枯草杆菌酶的至少一个结构部分,其所述部分中的改变预计导致改变的特性;
d)修饰编码亲本TY145枯草杆菌酶的核酸序列,以产生核酸序列,其核酸序列编码所述结构部分相应位置一个或多个氨基酸的缺失或替换,或所述结构部分相应位置一个或多个氨基酸的插入,并
e)在宿主细胞中表达修饰的核酸序列以产生变体TY145枯草杆菌酶。
5.根据权利要求4的方法,其中步骤a)中亲本TY145枯草杆菌酶赖以建模的TY145枯草杆菌酶与SEQ ID NO:1有至少63%的同源性,优选至少65%的同源性,更优选至少70%、更优选至少74%、更优选至少80%、更优选至少83%、更优选至少90%、更优选至少91%、更优选至少92%、更优选至少93%、更优选至少94%、更优选至少95%、更优选至少96%、更优选至少97%、更优选至少98%或甚至更优选与SEQ ID NO:1序列有至少99%的同源性。
6.根据权利要求4或5的方法,其中根据权利要求3定义步骤a)中亲本TY145枯草杆菌酶赖以建模的TY145枯草杆菌酶。
7.产生亲本枯草菌素家族枯草杆菌酶变体的方法,其变体与亲本枯草菌素家族枯草杆菌酶相比具有至少一种改变的特性,其方法包括:
a)在枯草菌素家族枯草杆菌酶三维结构上建立亲本枯草菌素家族枯草杆菌酶模型以产生亲本枯草菌素家族枯草杆菌酶的三维结构;
b)将步骤a)中得到的三维结构与TY145样枯草杆菌酶三维结构进行比较;
c)在步骤b)的比较基础上鉴定出亲本枯草菌素家族枯草杆菌酶的至少一个结构部分,其所述部分中的改变预计导致改变的特性;
d)修饰编码亲本枯草菌素家族枯草杆菌酶的核酸序列以产生核酸序列,其核酸序列编码所述结构部分相应位置一个或多个氨基酸的缺失或替换,或所述结构部分相应位置一个或多个氨基酸的插入,并
e)在宿主细胞中表达修饰的核酸序列以产生变体枯草菌素家族枯草杆菌酶。
8.根据权利要求7的方法,其中步骤a)中亲本枯草菌素家族枯草杆菌酶赖以建模的枯草菌素家族枯草杆菌酶与SEQ ID NO:5有至少61%的同源性,优选至少63%的同源性,优选至少65%的同源性,更优选至少70%、更优选至少74%、更优选至少80%、更优选至少83%、更优选至少90%、更优选至少91%、更优选至少92%、更优选至少93%、更优选至少94%、更优选至少95%、更优选至少96%、更优选至少97%、更优选至少98%或甚至更优选与SEQ ID NO:5序列有至少99%的同源性。
9.根据权利要求7或8的方法,其中步骤b)的TY145枯草杆菌酶的定义与权利要求3一致。
10.根据权利要求7-9中任一项的方法,其中步骤b)的TY145枯草杆菌酶与SEQ ID NO:1有至少63%的同源性,优选至少65%的同源性,更优选至少70%、更优选至少74%、更优选至少80%、更优选至少83%、更优选至少90%、更优选至少91%、更优选至少92%、更优选至少93%、更优选至少94%、更优选至少95%、更优选至少96%、更优选至少97%、更优选至少98%或甚至更优选与SEQ ID NO:1序列有至少99%的同源性。
11.产生亲本TY145样枯草杆菌酶变体的方法,其变体与亲本TY145样枯草杆菌酶相比至少具有一种改变的特性,方法包括:
a)在TY145样枯草杆菌酶三维结构上建立亲本TY145样枯草杆菌酶模型,以产生亲本TY145样枯草杆菌酶的三维结构;
b)将步骤a)中得到的三维结构与枯草菌素家族枯草杆菌酶三维结构进行比较;
c)在步骤b)的比较基础上鉴定出亲本TY145样枯草杆菌酶的至少一个结构部分,其所述部分中的改变预计导致改变的特性;
d)修饰编码亲本TY145样枯草杆菌酶的核酸序列,以产生核酸序列,其核酸序列编码所述结构部分相应位置一个或多个氨基酸的缺失或替换,或所述结构部分相应位置一个或多个氨基酸的插入,并
e)在宿主细胞中表达修饰的核酸序列以产生变体TY145样枯草杆菌酶。
12.根据权利要求11的方法,其中步骤b)的枯草菌素家族枯草杆菌酶与SEQ ID NO:5有至少61%的同源性,优选至少63%的同源性,优选至少65%的同源性,更优选至少70%、更优选至少74%、更优选至少80%、更优选至少83%、更优选至少90%、更优选至少91%、更优选至少92%、更优选至少93%、更优选至少94%、更优选至少95%、更优选至少96%、更优选至少97%、更优选至少98%或甚至更优选与SEQ ID NO:5序列有至少99%的同源性。
13.根据权利要求11或12的方法,其中亲本TY145样枯草杆菌酶的定义与权利要求3一致。
14.根据权利要求11-13中任一项的方法,其中亲本TY145样枯草杆菌酶与SEQ ID NO:1有至少63%的同源性,优选至少65%的同源性,更优选至少70%、更优选至少74%、更优选至少80%、更优选至少83%、更优选至少90%、更优选至少91%、更优选至少92%、更优选至少93%、更优选至少94%、更优选至少95%、更优选至少96%、更优选至少97%、更优选至少98%或甚至更优选与SEQ ID NO:1序列有至少99%的同源性。
15.枯草杆菌酶变体,其包含位于与TY145的离子结合位点之一距离不大于10_的一个或多个位置的改变,其中如SEQ ID NO:1所说明,位于与以下位置不大于10_的位置:
a)弱离子结合位点为:154、155、158、164、165、166、167、168、178、179、180、181、182、183、184、185、186、187、188、189、190、191、211、220、221、222、223、224、225、226、227、228、277、281和305,
b)近离子结合位点为:185、211、212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、227、277、281、299、300、301、304、305,
c)远离子结合位点为:193、198、199、201、202、204、216、217、219、226、227、228、229、284、285、286、287、288、289、290、291、292、293、294、295、296、297、298、299、300、301、302、303、304、305、306和307,
16.根据权利要求15的枯草杆菌酶变体,其中改变为以下替换中的一个或多个:I220S、T、D、E;T215S、D、E;G298A、S、T、D、E;G296A、S、T、D、E;V185T、D、E;I221N、D、T、E。
17.含有引入相应于枯草菌素家族枯草杆菌酶的强离子结合位点的离子结合位点的枯草杆菌酶变体,其中所述变体缺失了SEQ ID NO:1中H83-G90区域或H83-G90区域中至少一个氨基酸残基,并继而在A82和V91残基间插入一个或多个氨基酸残基,优选插入序列LNNSIG(SEQ IDNO:48)。
18.去除了一个或多个离子结合位点的TY145样枯草杆菌酶变体,其中所述变体含有以下改变中的一个或全部:
a)缺失SEQ ID NO:1中K290-D300区域或K290-D300区域中至少一个氨基酸残基,并继而在I289和Y301之间插入一个或多个氨基酸残基,优选插入序列GDS(SEQ ID NO:49)或DST(SEQ ID NO:50),并优选另外含有S303Y替换,
b)缺失SEQ ID NO:1中N212-R224区域或N212-R224区域中至少一个氨基酸残基,并继而在G211和D225之间插入一个或多个氨基酸残基,优选插入脯氨酸残基或丙氨酸残基。
19.TY145样枯草杆菌酶变体,其含有的一个或多个改变所在的一个或多个位置含于以下高活动区:
84、85、86、87和88,
108、109、110、111、112、113、114、115、116和117,
141、142、143、144、145和146,
150、151和152,
169、170和171,
200和201,
211、212、213、214、215、216、217、218、219和220,
242和243、
268、269和270.
20.TY145样枯草杆菌酶变体,其含有的一个或多个改变所在的一个或多个位置含于以下高活动区:
1、2、3、4、5、6和7,
17、18、19、20、21、22和23,
38、39、40、41、42、43、44、45、46、47、48、49和50,
57、58、59、60、61、62、63、64、65、66、67、68和69,
84、85、86、87、88、89、90、91和92,
107、108、109和110,
239、240、241、242和243
265和266,
其中所述改变优选在57-69区域或84-92区域中的一个或二者引入。
21.含有通过一个或多个以下修饰引入的一个或多个二硫键的TY145样枯草杆菌酶变体,所述修饰为:G26C+A95C;A167C+T254C;R203C+G292C;V228C+A284C,其中位置对应于SEQ ID NO:1中的位置。
22.含有D116H、K、R替换的TY145样枯草杆菌酶变体。
23.含有在SEQ ID NO:1的18、115、185、269和293中一个或多个位置的改变的TY145样枯草杆菌酶变体,其中优选的改变为Q18P、D115P、V185P、T269P和I293P。
24.TY145样枯草杆菌酶变体,其含有以下区域包含的一个或多个位置的改变:
16、17、18、19、20、21和22,
40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72和73,
118、119、120、121、122、123、124、125、126、127、128、129、130和131,
140、141、142、143、144、145、146、147、148、149、150、151、152、153、154、155、156、157,158、159、160和161,
275、276、277、278、279、280、281、282、283、284、285、286、287、288、289、290、291、292、293和294,
其中这类改变优选位于40-73和140-161区域的一个或二者中,优选在65-73和140-150亚区域中。
25.含有位于以下一个或多个位置的改变的TY145样枯草杆菌酶变体:SEQ ID NO:1的35、36、70、72、106、109、110、111、112、113、114、117、139、140、141、142、143、144、145、147、150、167、168、169、170、171、172、173、174、177、180、207、239、247、148、149、150、151和252。
26.含有位于以下一个或多个位置的改变的TY145样枯草杆菌酶变体:V31、V38、T79、V80、L81、V188、T254,其中优选变体含有V31I、T79S和V80A中的一个或多个。
27.含有天冬酰胺-甘氨酸序列的改变的TY145样枯草杆菌酶变体,其改变通过缺失或替换天冬酰胺或甘氨酸残基中至少一个实现,优选为天冬酰胺。
28.权利要求27的变体,其含有用选自A、Q、S、P、T和Y的氨基酸残基对天冬氨酸和/或甘氨酸的替换。
29.权利要求28的变体,其中替换在一个或多个以下位置进行:
球形芽孢杆菌:198-199,240-241;
TY145:87-88,109-110,199-200;
TA41:83-84,198-199;
TA39:88-89,198-199。
30.含有酪氨酸残基改变的TY145样枯草杆菌酶变体,其改变通过缺失或替换实现,优选替换为苯丙氨酸。
31.权利要求30的变体,其中替换在一个或多个以下位置进行:
球形芽孢杆菌:14、91、102、112、155、157、172、179、201、206、211、218、235、239、243、292、300;
TY145:15、39、92、103、113、156、158、202、219、240、244、287、301、307;
TA41:15、91、102、112、155、157、179、201、218、235、243;
TA39:15、61、91、102、112、155、157、173、179、201、211、218、235、243、267、281、284、292、293、296。
32.含有甲硫氨酸残基改变的TY145样枯草杆菌酶变体,其改变通过缺失或替换实现,优选替换为丝氨酸或丙氨酸残基。
33.权利要求32的变体,其中替换在一个或多个以下位置进行:
球形芽孢杆菌:138、251;
TY145:139、252;
TA41:1、138、251;
TA39:1、138、251。
34.已去除强离子结合位点的枯草菌素家族枯草杆菌酶变体,其中所述变体含有L75-G80(BPN′编号)区域或其他枯草菌素家族枯草杆菌酶相应区域的缺失,或L75-G80(BPN′编号)区域或其他枯草菌素家族枯草杆菌酶相应区域中至少一个氨基酸残基的缺失,并继而含有在A74和V81之间插入一个或多个氨基酸残基,优选插入TY145(SEQ ID NO:1)位置84-88的GGSNG(SEQ ID NO:51)序列,并优选另外含有替换L80Y和Q2A、N中的一个或二者。
35.含有V28I、A、L;I35V、A、L;T71S;I72A、G、V;A73L、G;M175V、A和T224S、A中一个或多个改变的BPN’样枯草杆菌酶变体,其中优选的Savinase变体含有替换V28I、I35V、T71S、I72A、A73L、M175V和T224S(BPN′编号)中的一个或多个,特别是含有组合V28I+I35V、V28I+T71S、V28I+I72A、V28I+A73L、V28I+M175V、I35V+T71S、I35V+I72A、I35V+A73L、I35V+A73L、I35V+M175V、T71S+I72A、T71S+A73L、T71S+A73L、T71S+M175V、I72A+A73L、I72A+A73L、I72A+M175V、A73L+M175V的变体。
36.含有一个或多个以下改变的BPN′样枯草杆菌酶变体:
a)缺失Savinase(BPN′编号)中的残基PSPSATLEQAVN(SEQ IDNO:23)(位置129-140)并继而在Savinase S128和S141之间插入TY145来源的残基SAKDSLIASAVD(SEQ ID NO:22)(位置144-155),
b)缺失Savinase(BPN′编号)中的残基SGNSGAGSISYPARYA(SEQ ID NO:25)(位置153-172)并继而在Savinase A152和N173之间插入TY145来源的残基AGNSGSGSNTIGFPGGLV(SEQ ID NO:24)(位置168-185),
c)缺失Savinase(BPN′编号)中的残基VNVQSTYPGSTYASLN(SEQ ID NO:27)(位置203-218)并继而在Savinase G202和G219之间插入TY145来源的残基ASVESTWYTGGYNTIS(SEQ ID NO:26)(位置233-248)。
37.含有一个或全部以下改变的BPN’样枯草杆菌酶变体:
a)缺失Savinase(BPN′编号)中的残基LSLGSPS(SEQ ID NO:29)(位置124-130)并继而在Savinase N123和P131之间插入TA39枯草杆菌酶来源的残基MSLGSSG(SEQ ID NO:28)(位置138-144),
b)缺失Savinase变体V104S(BPN′编号)中的残基LSLGSPSPSATL(SEQ ID NO:31)(位置124-135)并继而在Savinase变体V104S N123和E136之间插入TA39枯草杆菌酶来源的残基MSLGSSGESSLI(SEQ IDNO:30)(位置138-149)。
38.含有一个或多个以下改变的BPN’样枯草杆菌酶变体:
a)缺失Savinase(BPN′编号)中的残基VQAPAAHN(SEQ ID NO:33)(位置11-18)并继而在Savinase R10和R19之间插入TA39枯草杆菌酶来源的残基NNSSITQT(SEQ ID NO:32)(位置16-23),
b)缺失Savinase(BPN′编号)中的残基VPG*EPST(SEQ ID NO:35)(位置51-58)并继而在Savinase F50和Q59之间插入TA39枯草杆菌酶来源的残基TVGTTYTN(SEQ ID NO:34位置56-63),
c)缺失Savinase(BPN′编号)中的残基GN(位置61-62)并继而在Savinase D60和G63之间插入TA39枯草杆菌酶来源的残基RQ(位置69-70),
d)缺失Savinase(BPN′编号)中的残基PSPSATL(SEQ ID NO:37)(位置129-135)并继而在Savinase S128和E136之间插入TA39枯草杆菌酶来源的残基SGESSLI(SEQ ID NO:36)(位置143-149),
e)缺失Savinase(BPN′编号)中的残基YPGSTYASL(SEQ ID NO:39)(位置209-217)并继而在Savinase T208和N218之间插入TA39枯草杆菌酶来源的残基WFDGGYATI(SEQ ID NO:38)(位置238-246)。
39.含有一个或多个以下改变的BPN’样枯草杆菌酶变体:
a)缺失Savinase(BPN′编号)中的残基VPG*EPST(SEQ ID NO:41)(位置51-58)并继而在Savinase F50和Q59之间插入TA41枯草杆菌酶来源的残基TVGTNFTD(SEQ ID NO:40)(位置56-63),
b)缺失Savinase(BPN′编号)中的残基ALNNSI(SEQ ID NO:43)(位置74-79)并继而在Savinase A73和G80之间插入TA41枯草杆菌酶来源的残基TVGTNFTD(SEQ ID NO:40)(位置56-63)NGGTGS(SEQ ID NO:42)(位置83-88),
c)缺失Savinase(BPN′编号)中的残基ASGSGSV(SEQ ID NO:45)(位置98-104)并继而在Savinase G97和S10之间插入TA41枯草杆菌酶来源的残基DDGSGYA(SEQ ID NO:44)(位置107-113),
d)缺失Savinase(BPN′编号)中的残基KQKNPSW(SEQ ID NO:47)(位置235-241)并继而在Savinase V234和S242之间插入TA41枯草杆菌酶来源的残基WAQSPAA(SEQ ID NO:46)(位置264-270)。
40.分离的核酸序列,其含有编码前述权利要求中任一项定义或产生的枯草杆菌酶或枯草杆菌酶变体的核酸序列。
41.根据权利要求40的分离的的核酸序列,其核酸序列选自:
a)与SEQ ID NO:20或SEQ ID NO:21中展示的核酸序列具有至少40%同源性的核酸序列,和
b)在低严谨条件下,优选在中严谨条件下,特别是在高严谨条件下,与c)杂交的核酸序列,
c)SEQ ID NO:20或SEQ ID NO:21中展示的核酸序列的互补链,或
d)a)或b)或c)中任一序列的至少100个核苷酸的亚序列。
42.根据权利要求41的分离的核酸序列,其中核酸序列与SEQ IDNO:20或SEQ ID NO:21中展示的核酸序列具有至少45%、至少50%、至少55%、至少60%、至少65%、至少70%、至少75%、至少80%、至少85%、至少90%、至少91%、至少92%、至少93%、至少94%、至少95%、至少96%、至少97%、至少98%,或至少99%的同源性。
43.含有权利要求40-42中任一项所定义的核酸序列的分离的核酸构建体,该构建体与一个或多个能指导多肽在适当的表达宿主中表达的控制序列有效连接。
44.含有权利要求43的核酸构建体的重组宿主细胞。
45.产生权利要求1-39中任一项定义或产生的枯草杆菌酶或枯草杆菌酶变体的方法,其方法包括:
a)在有利于产生枯草杆菌酶变体的条件下培养权利要求41的重组宿主细胞,并
b)回收变体。
46.含有权利要求1-39中任一项定义或产生的枯草杆菌酶或枯草杆菌酶变体的洗涤剂组合物。
47.权利要求1-39中任一项定义或产生的枯草杆菌酶或枯草杆菌酶变体在清洁或洗涤应用中的用途。
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