Three-Dimensional Structure of Dopamine 3-Subtype Receptor with the Active Site Residues for the Binding of Dopamine
文献类型：期刊论文
| 作者 | Jin Yi1; Wang Yue1; Bian Fu-Yong1; Shi Qiang2; Ge Mao-Fa2; Wang Shu3; Zhang Xing-Kang2; Xu Si-Chuan1,2 |
| 刊名 | ACTA PHYSICO-CHIMICA SINICA
 |
| 出版日期 | 2011-10-01 |
| 卷号 | 27期号:10页码:2432-2446 |
| 关键词 | Ab Initio Dopamine 3-subtype Receptor 3pbl Active Site Molecular Dynamics Simulation Homology Modeling |
| ISSN号 | 1000-6818 |
| DOI | 10.3866/PKU.WHXB20111001 |
| 英文摘要 | The dopamine 3-subtype receptor (D3R) is a promising therapeutic target for the development of new drugs. Using rhodopsin as a template protein, we report homology modeling of a complete D3R structure including dopamine (Dop) in an environment of a 1-palmitoyl-2-oleoylsn-glycero-3-phospha-tidyl-choline (POPC) explicit lipid bilayer and water. A 300 ns molecular dynamics (MD) simulation was performed to obtain a stable three-dimensional structure for D3R (2B08-D3R) based on five residues (Asp117, His272, Phe269, Ser208, and Thr276), and these were validated as active sites for the binding of dopamine to the D3R protein by the binding energies (E-b) calculated using MP2/6-31G(d,p) between Dop and each of the residues within 0.6 nm of Dop. The five key residues are locating on TM3, TM5, and TM6 within the D3R helical regions, respectively, forming an active pocket for the binding of Dop to the D3R protein. The phenyl plane of Dop is parallel to the cylinder space formed by the TM2-TM7 helical regions when it bonds non-covalently to the D3R protein. The value of E-b between the Dop and D3R protein is -97.8 kJ.mol(-1), which explains why dopamine is easily assimilated into the D3R protein and departs from it as a nerve material and a signal transducer. Using the crystal protein structure of mutated D3R (code: 3PBL) we built another D3R protein structure including dopamine (designated Dop-3PBL-D3R) and identified five residues (Asp83, His272, Phe269, Phe268, and Trp265) as the active sites for the binding of Dop. The phenyl plane of Dop is also parallel to the cylinder space that is formed by the TM2-TM7 helical regions when it binds non-covalently to the Dop-3PBL-D3R protein with an E-b of -80.5 kJ.mol(-1) between them. |
| 语种 | 英语 |
| WOS记录号 | WOS:000295380300028 |
| 出版者 | PEKING UNIV PRESS |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/72331]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Xu Si-Chuan |
| 作者单位 | 1.Yunnan Univ, Key Lab, Coll Chem Sci & Technol, Educ Minist Med Chem Nat Resource, Kunming 650091, Peoples R China 2.Chinese Acad Sci, State Key Lab Struct Chem Unstable & Stable Speci, Beijing Natl Lab Mol Sci, Inst Chem, Beijing 100190, Peoples R China 3.Chinese Acad Sci, Inst Chem, CAS Key Lab Organ Solids, Beijing 100190, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jin Yi,Wang Yue,Bian Fu-Yong,et al. Three-Dimensional Structure of Dopamine 3-Subtype Receptor with the Active Site Residues for the Binding of Dopamine[J]. ACTA PHYSICO-CHIMICA SINICA,2011,27(10):2432-2446. |
| APA | Jin Yi.,Wang Yue.,Bian Fu-Yong.,Shi Qiang.,Ge Mao-Fa.,...&Xu Si-Chuan.(2011).Three-Dimensional Structure of Dopamine 3-Subtype Receptor with the Active Site Residues for the Binding of Dopamine.ACTA PHYSICO-CHIMICA SINICA,27(10),2432-2446. |
| MLA | Jin Yi,et al."Three-Dimensional Structure of Dopamine 3-Subtype Receptor with the Active Site Residues for the Binding of Dopamine".ACTA PHYSICO-CHIMICA SINICA 27.10(2011):2432-2446. |
入库方式： OAI收割
来源：化学研究所
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