白眉蝮蛇降纤酶的同源模建及B细胞抗原表位预测

被引:3
作者
贾秋磊
王林
陈鹏
杨青
姜秀萍
机构
[1] 大连理工大学生命科学与技术学院
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;
D O I
暂无
中图分类号
R392.1 [免疫生物学];
学科分类号
100102 ;
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。
引用
收藏
页码:97 / 102
页数:6
相关论文
共 10 条
[1]  
Molecular mechanism analysis of Gloydius shedaoensis venom gloshedobin interaction with inhibitors by homology modeling.[J].Xiuping Jiang;Lei Chen;Jianqiang Xu;Qing Yang.International Journal of Biological Macromolecules.2010, 1
[2]   Removal of B cell epitopes as a practical approach for reducing the immunogenicity of foreign protein-based therapeutics [J].
Nagata, Satoshi ;
Pastan, Ira .
ADVANCED DRUG DELIVERY REVIEWS, 2009, 61 (11) :977-985
[3]  
Snake venom components and their applications in biomedicine.[J].D. C. I. Koh;A. Armugam;K. Jeyaseelan.Cellular and molecular life sciences : CMLS.2007, 24
[4]   Stepwise prediction of conformational discontinuous B-Cell Epitopes using the mapitope algorithm [J].
Bublil, Erez M. ;
Freund, Natalia Tarnovitski ;
Mayrose, Itay ;
Penn, Osnat ;
Roitburd-Berman, Anna ;
Rubinstein, Nimrod D. ;
Pupko, Tal ;
Gershoni, Jonathan M. .
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 2007, 68 (01) :294-304
[5]   Practical applications of snake venom toxins in haemostasis [J].
Marsh, N ;
Williams, V .
TOXICON, 2005, 45 (08) :1171-1181
[6]   Therapeutic choices for patients with hemophilia and high-titer inhibitors [J].
Kulkarni, R ;
Aledort, LM ;
Berntorp, E ;
Brackman, HH ;
Brown, D ;
Cohen, AR ;
Ewing, NP ;
Gringeri, A ;
Gruppo, R ;
Hoots, K ;
Leissenger, C ;
Peerlinck, K ;
Poon, MC ;
Wong, WY .
AMERICAN JOURNAL OF HEMATOLOGY, 2001, 67 (04) :240-246
[7]   Structural features of a snake venom thrombin-like enzyme: thrombin and trypsin on a single catalytic platform? [J].
Castro, HC ;
Silva, DM ;
Craik, C ;
Zingali, RB .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2001, 1547 (02) :183-195
[8]   The crystal structure of the novel snake venom plasminogen activator TSV-PA: a prototype structure for snake venom serine proteinases [J].
Parry, MAA ;
Jacob, U ;
Huber, R ;
Wisner, A ;
Bon, C ;
Bode, W .
STRUCTURE WITH FOLDING & DESIGN, 1998, 6 (09) :1195-1206
[9]  
Recombinant Staphylokinase Variants With Altered Immunoreactivity: IV: Identification of Variants With Reduced Antibody Induction but Intact Potency.[J].Desire Collen;Luc Stockx;Henri Lacroix;Raphael Suy;Steven Vanderschueren.Circulation.1997, 2
[10]   降纤酶致过敏反应1例报告 [J].
郎素芹 ;
孙兆丽 ;
祝玮 .
齐鲁护理杂志, 2006, (03) :194-194