Crystal Structure of the Human Cannabinoid Receptor CB1
2016
Source PublicationCELL
ISSN0092-8674
Volume167Issue:3Pages:750-762
Status已发表
DOI10.1016/j.cell.2016.10.004
Abstract

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.

Indexed BySCI
Funding ProjectU.S. Department of Energy, Office of Science, Office of Basic Energy Sciences[DE-AC02-06CH11357]
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000386344100021
PublisherCELL PRESS
WOS KeywordPROTEIN-COUPLED RECEPTORS ; MOLECULAR-DYNAMICS SIMULATIONS ; MEMBRANE-PROTEINS ; INVERSE AGONIST ; SYNTHETIC CANNABINOIDS ; CYSTEINE RESIDUES ; ACCURATE DOCKING ; LIGAND AFFINITY ; BINDING ; ANTAGONIST
Original Document TypeArticle
Citation statistics
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1060
CollectioniHuman研究所
iHuman研究所_特聘教授组_Raymond Stevens组
iHuman研究所_PI研究组_刘志杰组
iHuman研究所_PI研究组_赵素文组
iHuman研究所_PI研究组_水雯箐组
iHuman研究所_PI研究组_华甜组
Corresponding AuthorLiu, Zhi-Jie
Affiliation
1.ShanghaiTech Univ, iHuman Inst, Shanghai 201210, Peoples R China
2.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
3.Northeastern Univ, Dept Pharmaceut Sci, Ctr Drug Discovery, Boston, MA 02115 USA
4.Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA
5.Univ Southern Calif, Dept Biol Sci, Bridge Inst, Los Angeles, CA 90089 USA
6.Univ Southern Calif, Dept Chem, Bridge Inst, Los Angeles, CA 90089 USA
7.Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA
8.Scripps Res Inst, Dept Neurosci, Jupiter, FL 33458 USA
9.Univ Calif San Diego, La Jolla, CA 92093 USA
10.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
11.GPCR Consortium, San Marcos, CA 92078 USA
First Author AffilicationiHuman Institute
Corresponding Author AffilicationiHuman Institute
First Signature AffilicationiHuman Institute
Recommended Citation
GB/T 7714
Hua, Tian,Vemuri, Kiran,Pu, Mengchen,et al. Crystal Structure of the Human Cannabinoid Receptor CB1[J]. CELL,2016,167(3):750-762.
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),750-762.
MLA Hua, Tian,et al."Crystal Structure of the Human Cannabinoid Receptor CB1".CELL 167.3(2016):750-762.
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