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5xr8

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Revision as of 16:29, 22 January 2020

Crystal structure of the human CB1 in complex with agonist AM841

Structural highlights

5xr8 is a 1 chain structure with sequence from Desvh. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Gene:	CNR1, CNR (DESVH)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

Publication Abstract from PubMed

The cannabinoid receptor 1 (CB1) is the principal target of the psychoactive constituent of marijuana, the partial agonist Delta9-tetrahydrocannabinol (Delta9-THC). Here we report two agonist-bound crystal structures of human CB1 in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 A and 2.95 A resolution, respectively. The two CB1-agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region. In addition, a 'twin toggle switch' of Phe2003.36 and Trp3566.48 (superscripts denote Ballesteros-Weinstein numbering) is experimentally observed and appears to be essential for receptor activation. The structures reveal important insights into the activation mechanism of CB1 and provide a molecular basis for predicting the binding modes of Delta9-THC, and endogenous and synthetic cannabinoids. The plasticity of the binding pocket of CB1 seems to be a common feature among certain class A G-protein-coupled receptors. These findings should inspire the design of chemically diverse ligands with distinct pharmacological properties.

Crystal structures of agonist-bound human cannabinoid receptor CB1.,Hua T, Vemuri K, Nikas SP, Laprairie RB, Wu Y, Qu L, Pu M, Korde A, Jiang S, Ho JH, Han GW, Ding K, Li X, Liu H, Hanson MA, Zhao S, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ Nature. 2017 Jul 27;547(7664):468-471. doi: 10.1038/nature23272. Epub 2017 Jul 5. PMID:28678776^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ryberg E, Vu HK, Larsson N, Groblewski T, Hjorth S, Elebring T, Sjogren S, Greasley PJ. Identification and characterisation of a novel splice variant of the human CB1 receptor. FEBS Lett. 2005 Jan 3;579(1):259-64. PMID:15620723 doi:http://dx.doi.org/10.1016/j.febslet.2004.11.085
↑ Hua T, Vemuri K, Nikas SP, Laprairie RB, Wu Y, Qu L, Pu M, Korde A, Jiang S, Ho JH, Han GW, Ding K, Li X, Liu H, Hanson MA, Zhao S, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. Crystal structures of agonist-bound human cannabinoid receptor CB1. Nature. 2017 Jul 27;547(7664):468-471. doi: 10.1038/nature23272. Epub 2017 Jul 5. PMID:28678776 doi:http://dx.doi.org/10.1038/nature23272

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5xr8"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human CB1 in complex with agonist AM841==
-<StructureSection load='5xr8' size='340' side='right' caption='[[5xr8]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
+<StructureSection load='5xr8' size='340' side='right'caption='[[5xr8]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5xr8]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Desvh Desvh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XR8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XR8 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8D0:(6aR,9R,10aR)-3-(8-azanyl-2-methyl-octan-2-yl)-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-1-ol'>8D0</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8D0:(6~{a}~{R},9~{R},10~{a}~{R})-9-(hydroxymethyl)-3-(8-isothiocyanato-2-methyl-octan-2-yl)-6,6-dimethyl-6~{a},7,8,9,10,10~{a}-hexahydrobenzo[c]chromen-1-ol'>8D0</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNR1, CNR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=882 DESVH])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5xr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xr8 OCA], [http://pdbe.org/5xr8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xr8 RCSB], [http://www.ebi.ac.uk/pdbsum/5xr8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xr8 ProSAT]</span></td></tr>
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Desvh]]
+[[Category: Large Structures]]
 [[Category: Bohn, L M]]
 [[Category: Ding, K]]

5xr8

From Proteopedia

Revision as of 16:29, 22 January 2020

Crystal structure of the human CB1 in complex with agonist AM841

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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