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Three-Dimensional Structure of Dopamine 3-Subtype Receptor with the Active Site Residues for the Binding of Dopamine
Jin Yi1; Wang Yue1; Bian Fu-Yong1; Shi Qiang2; Ge Mao-Fa2; Wang Shu3; Zhang Xing-Kang2; Xu Si-Chuan1,2
2011-10-01
Source PublicationACTA PHYSICO-CHIMICA SINICA
ISSN1000-6818
Volume27Issue:10Pages:2432-2446
AbstractThe 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.
KeywordAb Initio Dopamine 3-subtype Receptor 3pbl Active Site Molecular Dynamics Simulation Homology Modeling
DOI10.3866/PKU.WHXB20111001
Indexed BySCI
Language英语
WOS IDWOS:000295380300028
PublisherPEKING UNIV PRESS
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/72332
Collection中国科学院化学研究所
Corresponding AuthorXu Si-Chuan
Affiliation1.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
Recommended Citation
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.
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