Crystal Structure of the Human Cannabinoid Receptor CB1

doi:10.1016/j.cell.2016.10.004

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	Crystal Structure of the Human Cannabinoid Receptor CB1
	Hua, Tian 6,7; Vemuri, Kiran 8,9; Pu, Mengchen 6; Qu, Lu 6,7; Han, Gye Won 1,10; Wu, Yiran 7; Zhao, Suwen 7; Shui, Wenqing 7; Li, Shanshan 7; Korde, Anisha 8,9
刊名	CELL
	2016-10-20
卷号	167 期号:3 页码:750-+
ISSN号	0092-8674
DOI	10.1016/j.cell.2016.10.004
文献子类	Article
英文摘要	Cannabinoid receptor 1 (CB1) is the principal target of Delta(9)-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 angstrom crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding. In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.
资助项目	Ministry of Science and Technology of China[2014CB910400] ; Ministry of Science and Technology of China[2015CB910104] ; National Nature Science Foundation of China[31330019] ; National Institutes of Health[P01DA009158] ; National Institutes of Health[R37DA023142] ; National Institutes of Health[R01AI118985] ; NSF[00000000] ; Shanghai Municipal Government[00000000] ; ShanghaiTech University[00000000] ; GPCR Consortium[00000000] ; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences[DE-AC02-06CH11357] ; Cloning, Cell Expression, and Protein Purification Core Facilities of iHuman Institute[00000000]
WOS关键词	PROTEIN-COUPLED RECEPTORS ; MOLECULAR-DYNAMICS SIMULATIONS ; MEMBRANE-PROTEINS ; INVERSE AGONIST ; SYNTHETIC CANNABINOIDS ; CYSTEINE RESIDUES ; ACCURATE DOCKING ; LIGAND AFFINITY ; BINDING ; ANTAGONIST
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000386344100021
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275852]
专题	药物靶标结构与功能中心
通讯作者	Liu, Zhi-Jie
作者单位	1.Univ Southern Calif, Dept Chem, Bridge Inst, Los Angeles, CA 90089 USA; 2.Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA; 3.Univ Calif San Diego, La Jolla, CA 92093 USA; 4.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 5.GPCR Consortium, San Marcos, CA 92078 USA 6.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China; 7.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China; 8.Northeastern Univ, Dept Pharmaceut Sci, Ctr Drug Discovery, Boston, MA 02115 USA; 9.Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA; 10.Univ Southern Calif, Dept Biol Sci, Bridge Inst, Los Angeles, CA 90089 USA;
推荐引用方式 GB/T 7714	Hua, Tian,Vemuri, Kiran,Pu, Mengchen,et al. Crystal Structure of the Human Cannabinoid Receptor CB1[J]. CELL,2016,167(3):750-+.
APA	Hua, Tian.,Vemuri, Kiran.,Pu, Mengchen.,Qu, Lu.,Han, Gye Won.,...&Liu, Zhi-Jie.(2016).Crystal Structure of the Human Cannabinoid Receptor CB1.CELL,167(3),750-+.
MLA	Hua, Tian,et al."Crystal Structure of the Human Cannabinoid Receptor CB1".CELL 167.3(2016):750-+.