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Structural Features for Functional Selectivity at Serotonin Receptors

文献类型：期刊论文

作者Wacker, Daniel3; Wang, Chong3; Katritch, Vsevolod3; Han, Gye Won3; Huang, Xi-Ping2,4; Vardy, Eyal2,4; McCorvy, John D.2,4; Jiang, Yi3,5; Chu, Meihua3; Siu, Fai Yiu3
刊名SCIENCE
出版日期2013-05-03
卷号340期号:6132页码:615-619
ISSN号0036-8075
DOI10.1126/science.1232808
文献子类Article
英文摘要Drugs active at G protein-coupled receptors (GPCRs) can differentially modulate either canonical or noncanonical signaling pathways via a phenomenon known as functional selectivity or biased signaling. We report biochemical studies showing that the hallucinogen lysergic acid diethylamide, its precursor ergotamine (ERG), and related ergolines display strong functional selectivity for beta-arrestin signaling at the 5-HT2B 5-hydroxytryptamine (5-HT) receptor, whereas they are relatively unbiased at the 5-HT1B receptor. To investigate the structural basis for biased signaling, we determined the crystal structure of the human 5-HT2B receptor bound to ERG and compared it with the 5-HT1B/ERG structure. Given the relatively poor understanding of GPCR structure and function to date, insight into different GPCR signaling pathways is important to better understand both adverse and favorable therapeutic activities.
WOS关键词PROTEIN-COUPLED RECEPTOR ; CRYSTAL-STRUCTURE ; PATHWAYS ; AGONISTS
资助项目National Institute of General Medical Sciences (NIGMS) Protein Structure Initiative[U54 GM094618] ; NIH[P50 GM073197] ; Jay and Betty Van Andel Foundation, Amway (China)[R01 DK071662] ; Ministry of Science and Technology (China)[2012ZX09301001-005] ; Ministry of Science and Technology (China)[2012CB910403] ; Ministry of Science and Technology (China)[U19 MH82441] ; Ministry of Science and Technology (China)[R01 MH61887] ; National Institute of Mental Health Psychoactive Drug Screening Program[00000000] ; Michael Hooker Chair of Pharmacology[00000000] ; Boehringer Ingelheim Fonds Ph.D. Fellowship[00000000] ; Receptos[00000000] ; GPCR structure-based drug discovery company[00000000] ; National Cancer Institute[Y1-CO-1020] ; NIGMS[Y1-GM-1104] ; 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:000318268900049
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/277625]  
专题药物靶标结构与功能中心
通讯作者Roth, Bryan L.
作者单位1.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA
2.Univ N Carolina, Sch Med, Dept Pharmacol, NIMH,Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA;
3.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA;
4.Univ N Carolina, Sch Med, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 USA;
5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Mat Med Ctr, Van Andel Res Inst,CAS Key Lab Receptor Res, Shanghai 200031, Peoples R China;
推荐引用方式
GB/T 7714		 Wacker, Daniel,Wang, Chong,Katritch, Vsevolod,et al. Structural Features for Functional Selectivity at Serotonin Receptors[J]. SCIENCE,2013,340(6132):615-619.
APA Wacker, Daniel.,Wang, Chong.,Katritch, Vsevolod.,Han, Gye Won.,Huang, Xi-Ping.,...&Stevens, Raymond C..(2013).Structural Features for Functional Selectivity at Serotonin Receptors.SCIENCE,340(6132),615-619.
MLA Wacker, Daniel,et al."Structural Features for Functional Selectivity at Serotonin Receptors".SCIENCE 340.6132(2013):615-619.

入库方式： OAI收割

来源：上海药物研究所

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