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Structural Basis for Molecular Recognition at Serotonin Receptors
文献类型：期刊论文
| 作者 | Wang, Chong2; Jiang, Yi2,3 ; Ma, Jinming2,4; Wu, Huixian2; Wacker, Daniel2; Katritch, Vsevolod2; Han, Gye Won2; Liu, Wei2; Huang, Xi-Ping5,6; Vardy, Eyal5,6
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| 刊名 | SCIENCE
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| 出版日期 | 2013-05-03 |
| 卷号 | 340期号:6132页码:610-614 |
| ISSN号 | 0036-8075 |
| DOI | 10.1126/science.1232807 |
| 文献子类 | Article |
| 英文摘要 | Serotonin or 5-hydroxytryptamine (5-HT) regulates a wide spectrum of human physiology through the 5-HT receptor family. We report the crystal structures of the human 5-HT1B G protein-coupled receptor bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures reveal similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family, clarifying the family-wide agonist activity of 5-HT. Compared with the structure of the 5-HT2B receptor, the 5-HT1B receptor displays a 3 angstrom outward shift at the extracellular end of helix V, resulting in a more open extended pocket that explains subtype selectivity. Together with docking and mutagenesis studies, these structures provide a comprehensive structural basis for understanding receptor-ligand interactions and designing subtype-selective serotonergic drugs. |
| WOS关键词 | PROTEIN-COUPLED RECEPTOR ; VALVULAR HEART-DISEASE ; CARDIAC VALVULOPATHY ; AGONIST ; SCHIZOPHRENIA ; FENFLURAMINE ; PHARMACOLOGY ; DISORDERS ; MUTATION ; LIGANDS |
| 资助项目 | National Institute of General Medical Sciences (NIGMS) PSI: Biology grant[U54 GM094618] ; National Institute of General Medical Sciences (NIGMS) PSI: Biology grant[GPCR-118] ; NIH Common Fund in Structural Biology grant[P50 GM073197] ; Jay and Betty Van Andel Foundation[R01 DK071662] ; Ministry of Science and Technology (China)[2012ZX09301001-005] ; Ministry of Science and Technology (China)[2012CB910403] ; Amway (China)[R01 MH61887] ; Amway (China)[U19 MH82441] ; Amway (China)[R01 DA27170] ; National Institute of Mental Health Psychoactive Drug Screening Program[00000000] ; Michael Hooker Chair of Pharmacology[00000000] ; Boehringer Ingelheim Fonds Ph.D. Fellowship[00000000] ; National Cancer Institute[Y1-CO-1020] ; NIGMS[Y1-GM-1104] ; Michigan Economic Development Corporation[00000000] ; Michigan Technology Tri-Corridor Grant[085P1000817] ; Office of Science of the U.S. Department of Energy[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000318268900048 |
| 出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277624]  |
| 专题 | 药物靶标结构与功能中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物发现与设计中心 |
| 通讯作者 | Stevens, Raymond C. |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Mat Med Ctr, Van Andel Res Inst,CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA; 5.Univ N Carolina, Sch Med, Dept Pharmacol, NIMH,Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA; 6.Univ N Carolina, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA; 7.Dalian Univ Technol, Fac Chem Environm & Biol Sci & Technol, State Key Lab Technol, Dept Engn Mech, Dalian 116023, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Wang, Chong,Jiang, Yi,Ma, Jinming,et al. Structural Basis for Molecular Recognition at Serotonin Receptors[J]. SCIENCE,2013,340(6132):610-614. |
| APA | Wang, Chong.,Jiang, Yi.,Ma, Jinming.,Wu, Huixian.,Wacker, Daniel.,...&Xu, H. Eric.(2013).Structural Basis for Molecular Recognition at Serotonin Receptors.SCIENCE,340(6132),610-614. |
| MLA | Wang, Chong,et al."Structural Basis for Molecular Recognition at Serotonin Receptors".SCIENCE 340.6132(2013):610-614. |
入库方式： OAI收割
来源：上海药物研究所
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