5TGZ

Crystal Structure of the Human Cannabinoid Receptor CB1

Summary for 5TGZ

• Entry DOI: 10.2210/pdb5tgz/pdb
• Descriptor: Cannabinoid receptor 1,Flavodoxin,Cannabinoid receptor 1, 4-[4-[2-(2,4-dichlorophenyl)-4-methyl-5-(piperidin-1-ylcarbamoyl)pyrazol-3-yl]phenyl]but-3-ynyl nitrate, FLAVIN MONONUCLEOTIDE, ... (7 entities in total)
• Functional Keywords: membrane protein, g protein-coupled receptor, human cannabinoid receptor cb1, marijuana, stabilizing antagonist am6538, lipidic cubic phase, cb1-flavodoxin chimera, signaling protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 52646.18

Authors

Hua, T.,Vemuri, K.,Pu, M.,Qu, L.,Han, G.W.,Wu, Y.,Zhao, S.,Shui, W.,Li, S.,Korde, A.,Laprairie, R.B.,Stahl, E.L.,Ho, J.H.,Zvonok, N.,Zhou, H.,Kufareva, I.,Wu, B.,Zhao, Q.,Hanson, M.A.,Bohn, L.M.,Makriyannis, A.,Stevens, R.C.,Liu, Z.J. (deposition date: 2016-09-28, release date: 2016-11-02, Last modification date: 2024-10-30)

Primary citation

Hua, T.,Vemuri, K.,Pu, M.,Qu, L.,Han, G.W.,Wu, Y.,Zhao, S.,Shui, W.,Li, S.,Korde, A.,Laprairie, R.B.,Stahl, E.L.,Ho, J.H.,Zvonok, N.,Zhou, H.,Kufareva, I.,Wu, B.,Zhao, Q.,Hanson, M.A.,Bohn, L.M.,Makriyannis, A.,Stevens, R.C.,Liu, Z.J.
Crystal Structure of the Human Cannabinoid Receptor CB1.
Cell, 167:750-762.e14, 2016

PubMed Abstract: Cannabinoid receptor 1 (CB) is the principal target of Δ-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB 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 Å crystal structure of human CB in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB-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 CB ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB and provides new opportunities for the design of next-generation CB-targeting pharmaceuticals.

PubMed: 27768894
DOI: 10.1016/j.cell.2016.10.004

Experimental method

X-RAY DIFFRACTION (2.8 Å)