白眉蝮蛇降纤酶的同源模建及B细胞抗原表位预测  

Homology Modeling and B Cell Antigenic Epitopes Predicition of Defibrase from Agkistrodon hadys ussuriensis Snake Venom

作　　者：贾秋磊 王林[1] 陈鹏[1] 杨青[1] 姜秀萍[1] 

机构地区：[1]大连理工大学生命科学与技术学院,辽宁大连116023

出　　处：《华北农学报》2013年第S1期97-102,共6页Acta Agriculturae Boreali-Sinica

基　　金：国家自然科学基金项目(81102378);中央高校基本科研业务费专项资金(DUT11SM02)

摘　　要：白眉蝮蛇降纤酶是我国在临床上用来治疗血栓栓塞性疾病的国家基本药物。但该酶来源于蛇毒,是异源蛋白,且是大分子蛋白质,不可避免的存在免疫原性问题。另外该蛋白药物在我国使用规模很大,因此由免疫原性导致的安全性问题不容忽视。首先通过DNAStar软件和ABCpred、BCPREDS等服务器预测得到肽端AA27~35、44~50、66~72、79~98、101~109、117~127、134~142、151~164、179~188、194~206、221~233、247~260区域为白眉蝮蛇降纤酶的B细胞线性表位优势区域。然后以蝮蛇毒蛋白C激活剂蛋白的晶体结构为模板,利用MODELLER 9.10软件中的Pythonwin程序进行白眉蝮蛇降纤酶的同源模建,并利用PROCHECK、ERRAT及PROSA程序进行同源模建的合理化评价。根据白眉蝮蛇降纤酶的模建三维结构并结合DiscoTope和cons PPISP网络数据库预测B细胞构象型抗原表位。得到蛋白的N端45~51、81~90、95~106、134~141、153~159、177~182、225~232、251~257区段为白眉蝮蛇降纤酶的B细胞构象型表位区域。本项目的预期成果将为降纤酶药物的安全化应用提供新思路,为蛋白质药物免疫原性机制研究提供技术基础。Defibrase from Agkistrodon halys ussuriensis snake venom is essential medicine to be used in the clinical treatment of thromboembilic disease in our country .However,this enzyme derived from snake venom ,is a heterologous protein and is a macromolecular protein ,and therefore ,it's immunogenicity problem is inevitable .More-over,this protein drug was used in large scale in our country ,and therefore,the security issues caused by immunoge-nicity cannot be ignored .In this work,B cell linear epitopes were predicted using DNAStar soft ware and ABCpred , BCPREDS,BcePred,BepiPred 1.0 and Ellipro web servers.B-cell linear epitopes in defibrase were predicted to lo-cate in the regions of 27-35,44-50,66-72,79-98,101-109,117-127,134-142,151-164,179-188,194-206,221-233 and 247-260.Using protein C activator from Agkistrodon contortrix venom(ACC-C) as template,a 3D structure model of defibrase was constructed by Pythonwin program using modeling package MODELLER 9 .10 .Ste-reochemical quality of the selected model was evaluated using PROCHECK ,Errat and PROSA programs .The confor-mational epitopes of defibrase was predicted by 3D structure of homology modeling combined with Discotope 1.2 server and cons PPISP online tools .B-cell conformational epitopes in defibrase were predicted to locate in the re-gions of 45-51 ,81-90 ,95-106 ,134-141 ,153-159 ,177-182 ,225-232 and 251-257 .The expected results of the project are useful for providing new ideas for the safety applications of defibrase drugs ,and providing the tech-nical basis for immunogenicity mechanism of protein drugs .

关 键 词：降纤酶 免疫原性 线性表位 构象型表位 同源模建 长白山白眉蝮蛇 

分 类 号：R392.1[医药卫生—免疫学]