5u09

High-resolution crystal structure of the human CB1 cannabinoid receptor

spinqualitylabelsall models 5u09, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5u09 is a 1 chain structure with sequence from Homo sapiens and Pyrococcus abyssi GE5. This structure supersedes the now removed PDB entry 5tjv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.6Å Ligands: 7DY, PEG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9V2J8_PYRAB CNR1_HUMAN Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding. Publication Abstract from PubMed The human cannabinoid G-protein-coupled receptors (GPCRs) CB1 and CB2 mediate the functional responses to the endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG), as well as the widely consumed plant (phyto)cannabinoid Delta9-tetrahydrocannabinol (THC)1. The cannabinoid receptors have been the targets of intensive drug discovery efforts owing to the therapeutic potential of modulators for controlling pain2, epilepsy3, obesity4, and other maladies. Although much progress has recently been made in understanding the biophysical properties of GPCRs, investigations of the molecular mechanisms of the cannabinoids and their receptors have lacked high-resolution structural data. We used GPCR engineering and lipidic cubic phase (LCP) crystallization to determine the structure of the human CB1 receptor bound to the inhibitor taranabant at 2.6 A resolution. The extracellular surface of CB1, including the highly conserved membrane-proximal amino-terminal (N-terminal) region, is distinct from other lipid-activated GPCRs and forms a critical part of the ligand binding pocket. Docking studies further demonstrate how this same pocket may accommodate the cannabinoid agonist THC. Our CB1 structure provides an atomic framework for studying cannabinoid receptor function, and will aid the design and optimization of cannabinoid system modulators for therapeutic ends. High-resolution crystal structure of the human CB1 cannabinoid receptor.,Shao Z, Yin J, Chapman K, Grzemska M, Clark L, Wang J, Rosenbaum DM Nature. 2016 Nov 16. doi: 10.1038/nature20613. PMID:27851727 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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