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DOI | 10.1126/science.aan5468 |
D-4 dopamine receptor high-resolution structures enable the discovery of selective agonists | |
Wang, Sheng1; Wacker, Daniel1; Levit, Anat2; Che, Tao1; Betz, Robin M.3,4,5,6; McCorvy, John D.1; Venkatakrishnan, A. J.3,4,5; Huang, Xi-Ping1; Dror, Ron O.3,4,5,6; Shoichet, Brian K.2; Roth, Bryan L.1,7,8 | |
2017-10-20 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2017 |
卷号 | 358期号:6361页码:381-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D-4 dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D-4 dopamine receptor. The ability to efficiently exploit structure for specific probe discovery-rapidly moving from elucidating receptor structure to discovering previously unrecognized, selective agonists-testifies to the power of structure-based approaches. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000413251000046 |
WOS关键词 | CRYSTAL-STRUCTURE ; MOLECULAR DETERMINANTS ; D3 RECEPTORS ; PROTEIN ; SODIUM ; D2 ; COMPLEX ; 2ND |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/197152 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ North Carolina Chapel Hill, Dept Pharmacol, Chapel Hill, NC 27599 USA; 2.Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA; 3.Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA; 4.Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA; 5.Stanford Univ, Inst Computat & Math Engn, Stanford, CA 94305 USA; 6.Stanford Univ, Biophys Program, Stanford, CA 94305 USA; 7.Univ North Carolina Chapel Hill, Div Chem Biol & Med Chem, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA; 8.Univ North Carolina Chapel Hill, NIMH, Psychoact Drug Screening Program, Sch Med, Chapel Hill, NC 27599 USA |
推荐引用方式 GB/T 7714 | Wang, Sheng,Wacker, Daniel,Levit, Anat,et al. D-4 dopamine receptor high-resolution structures enable the discovery of selective agonists[J]. SCIENCE,2017,358(6361):381-+. |
APA | Wang, Sheng.,Wacker, Daniel.,Levit, Anat.,Che, Tao.,Betz, Robin M..,...&Roth, Bryan L..(2017).D-4 dopamine receptor high-resolution structures enable the discovery of selective agonists.SCIENCE,358(6361),381-+. |
MLA | Wang, Sheng,et al."D-4 dopamine receptor high-resolution structures enable the discovery of selective agonists".SCIENCE 358.6361(2017):381-+. |
条目包含的文件 | 条目无相关文件。 |
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