Molecular modeling of purinergic receptor P2Y12 and interaction with its antagonists
文献类型：期刊论文
| 作者 | Zhan, C; Yang, J; Dong, XC; Wang, YL |
| 刊名 | JOURNAL OF MOLECULAR GRAPHICS & MODELLING
 |
| 出版日期 | 2007 |
| 卷号 | 26期号:1页码:20-31 |
| 关键词 | P2Y12 ADP receptor antagonists ATP platelets aggregation |
| 通讯作者 | Yang, J (reprint author), Nanjing Univ, Dept Biochem, State Key Lab Pharmaceut Biotechnol, Life Coll, Nanjing 210093, Peoples R China.,luckyjyj@sina.com.cn |
| 英文摘要 | Purinergic receptors are a class of cell surface receptors for purines that prefer ATP or ADP over adenosine. The surface receptors for extracellular nucleotides are called P2 receptors. They are activated by both pyrimidine and purine nucleotides. ADP initiates platelet aggregation by 'simultaneous activation of two G protein-coupled receptors, P2Y1 and P2Y12. P2Y12 has been shown to be the target of the thienopyridine drugs, ticlopidine and clopidogrel. Here, the active sites of P2Y12 for ATP as well as ADP are predicted by bioinformatics and molecular modeling. First, the three-dimensional (3D) structure of P2Y12 was constructed by InsightII/Homology module using the corresponding bovine rhodopsin (PDB code: 1HZX) as the template. Then the primary structures were optimized by energy minimization that has been successfully accepted by the Protein Data Bank (PDB code: 1VZ1). Second, a simple scoring matrix was built up based on the analysis of 13 known ATP-binding proteins. And the most probable active sites of P2Y12 were predicted using the scoring matrix, which include three distant areas: "head area" (LGTGPLRTFV, 87-96), "middle area" (VGLITNGLAM, 38-47, and LGAKILSVVI, 139-148), and "bottom area" (RTRGVGKVPR, 222-231). Subsequently the structural model of P2Y12 was docked with ATP/ADP in comparison with P2Y1 (PDB code I ddd). As a comparison, we docked its antagonists, such as ticlopidine and clopidogrel, to the most probable sites and calculated their intermolecular energy. Our results imply that P2Y12 has the potential to be inhibited by ADP/ATP analogs, and it suggests that P2Y12 acts as a target of new drugs that inhibit platelet aggregation. (C) 2006 Elsevier Inc. All rights reserved. |
| 学科主题 | Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology |
| 类目[WOS] | Biochemical Research Methods ; Biochemistry & Molecular Biology ; Computer Science, Interdisciplinary Applications ; Crystallography ; Mathematical & Computational Biology |
| 关键词[WOS] | CRYSTAL-STRUCTURE ; PROTEIN-KINASE ; PLATELET-AGGREGATION ; P2 RECEPTORS ; ATP ; ADP ; INHIBITION ; ACTIVATION ; RESOLUTION ; COMPLEX |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000248646500003 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1503]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhan, C,Yang, J,Dong, XC,et al. Molecular modeling of purinergic receptor P2Y12 and interaction with its antagonists[J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING,2007,26(1):20-31. |
| APA | Zhan, C,Yang, J,Dong, XC,&Wang, YL.(2007).Molecular modeling of purinergic receptor P2Y12 and interaction with its antagonists.JOURNAL OF MOLECULAR GRAPHICS & MODELLING,26(1),20-31. |
| MLA | Zhan, C,et al."Molecular modeling of purinergic receptor P2Y12 and interaction with its antagonists".JOURNAL OF MOLECULAR GRAPHICS & MODELLING 26.1(2007):20-31. |
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