The metabolism of CYP2C9 and CYP2C19 for gliclazide by homology modeling and docking study
文献类型：期刊论文
| 作者 | Yao, Yuan2; Han, Wei-Wei2; Zhou, Yi-Han2; Li, Ze-Sheng2; Li, Qiang1; Chen, Xiao-Yan1 ; Zhong, Da-Fang1
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| 刊名 | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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| 出版日期 | 2009-02 |
| 卷号 | 44期号:2页码:854-861 |
| 关键词 | Cytochrome P450 protein Gliclazide Molecular docking Substrate inhibition |
| ISSN号 | 0223-5234 |
| DOI | 10.1016/j.ejmech.2008.04.015 |
| 文献子类 | Article |
| 英文摘要 | With homology modeling techniques, a 3D structure model of CYP2C19 was built and refined with molecular mechanics and molecular dynamics simulations. The refined model was assessed to be reasonable by Profile-3D and PROCHECK programs. With the aid of the automatic molecular docking, one substrate and two inhibitors were docked to CYP2C19 by InsightII/Affinity program. The docking results, which are in well agreement with the reported results, demonstrate that the refined model of CYP2C19 is reliable. Then, with the refined model of CYP2C19 and the crystal structure of CYP2C9, the metabolisms of them for gliclazide in two different metabolic pathways were studied and the results show that both enzymes have more favorable interaction energies and stronger affinity with gliclazide in methylhydroxylation pathway than in 6 beta-hydroxylation pathway. It is exciting that substrate inhibition phenomenon can be found in metabolisms of CYP2C9 and CYP2C19 for gliclazide in two metabolic pathways. Gliclazide can change the conformation of the active sites and decrease obviously the affinities between gliclazide in the active site and enzymes when it is docked in the second active sites in CYP2C9 and CYP2C19. These results are in well agreement with the kinetic experimental results. (c) 2008 Elsevier Masson SAS. All rights reserved. |
| WOS关键词 | TYPE-2 DIABETES-MELLITUS ; HUMAN CYTOCHROME P4502C9 ; ANTIDIABETIC AGENTS ; METFORMIN ; PHARMACOKINETICS ; SELECTIVITY ; INHIBITORS ; PROFILES ; KINETICS ; UPDATE |
| 资助项目 | National Science Foundation of China[20333050] ; National Science Foundation of China[20673044] ; Doctor Foundation by the Ministry of Education, Foundation[00000000] ; Ministry of Education[00000000] ; Ministry of Education of China[00000000] ; Jilin Province[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000264407800044 |
| 出版者 | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279331]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Li, Ze-Sheng |
| 作者单位 | 1.Chinese Acad Sci, Ctr Drug Metab Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Jilin Univ, Inst Theoret Chem, State Key Lab Theoret & Computat Chem, Changchun 130023, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Yao, Yuan,Han, Wei-Wei,Zhou, Yi-Han,et al. The metabolism of CYP2C9 and CYP2C19 for gliclazide by homology modeling and docking study[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2009,44(2):854-861. |
| APA | Yao, Yuan.,Han, Wei-Wei.,Zhou, Yi-Han.,Li, Ze-Sheng.,Li, Qiang.,...&Zhong, Da-Fang.(2009).The metabolism of CYP2C9 and CYP2C19 for gliclazide by homology modeling and docking study.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,44(2),854-861. |
| MLA | Yao, Yuan,et al."The metabolism of CYP2C9 and CYP2C19 for gliclazide by homology modeling and docking study".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 44.2(2009):854-861. |
入库方式： OAI收割
来源：上海药物研究所
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