文献类型：期刊文献

英文题名：Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking

作者：Li, Weihua[1];Tang, Yun[1];Liu, Hong[2];Cheng, Jiagao[1];Zhu, Weiliang[2];Jiang, Hualiang[1,2]

机构：[1]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Discovery & Design, Shanghai 201203, Peoples R China

年份：2008

卷号：71

期号：2

起止页码：938

外文期刊名：PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000254263400036)】；

语种：英文

外文关键词：cytochrome P450 2J2; homology modeling; molecular dynamics; molecular docking

摘要：Cytochrome P450 (P450) 2J2 catalyzes epoxidation of arachidonic acid to eicosatrienoic acids, which are related to a variety of diseases such as coronary artery disease, hypertension, and carcinogenesis. Recent experimental data also suggest that P450 2J2 could be a novel biomarker and a potential target for cancer therapy. However, the active site topology and substrate specificity of this enzyme remain unclear. In this study, a three-dimensional model of human P450 2J2 was first constructed on the basis of the crystal structure of human P450 2 9 in complex with a substrate using homology modeling method, an refined by molecular dynamics simulation. Flexible docking approaches were then employed to dock four ligands into the active site of P450 2J2 in order to probe the ligand-binding modes. By analyzing the results, active site architecture and certain key residues responsible for substrate specificity were identified on the enzyme, which might be very helpful for understanding the enzyme's biological role and providing insights for designing novel inhibitors of P450 2J2.