Abstract: Defibrase from Agkistrodou halys ussurieusis 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. Moreover this protein drug was used in large scale in our country and therefore,the security issues caused by immunogenicity cannot be ignored. In this work B cell linear epitopes were predicted using DNAStar soft ware and ABCpred,BCPREDS BcePred,B epiPred 1 .0 and Ellipro web servers. Bell linear epitopes in defibrase were predicted to locate in the regions of 27一35,44一50,66一72,79一98,101一109,117一127,134一142 151一164,179一188,194-206,221一233 and 247一260. Using protein C activator from Agkistrodou coutortrix venom (ACCT) as template,a 3D structure model of defibrase was constructed by Pythonwin program using modeling package MODELLER 9. 10. Stereochemical quality of the selected model was evaluated using PROCHECK, Errat and PROSA programs. The conformational epitopes of defibrase was predicted by 3 D structure of homology modeling combined with Discotope 1.2 server and cons PPISP online tools. Bell conformational epitopes in defibrase were predicted to locate in the regions of 45一51,81一90,95一106,134一141,153一159,177一182 225一232 and 251一257. The expected results of the project are useful for providing new ideas for the safety applications of defibrase drugs and providing the technical basis for immunogenicity mechanism of protein drugs.

Key words: Defibrase, Immunogenicity, Linear epitopes, Conformational eptiopes, Homology modeling, Agkistroddon halys ussuriensis

CLC Number: 

• R34