5tgz: Difference between revisions

Latest revision as of 10:52, 30 October 2024

Crystal Structure of the Human Cannabinoid Receptor CB1

Structural highlights

5tgz is a 1 chain structure with sequence from Desulfovibrio vulgaris str. Hildenborough and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	FMN, OLA, OLC, PEG, ZDG
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] FLAV_NITV2 Low-potential electron donor to a number of redox enzymes.

Publication Abstract from PubMed

Cannabinoid receptor 1 (CB1) is the principal target of Delta9-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 A 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.

Crystal Structure of the Human Cannabinoid Receptor CB1.,Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Ho JH, Zvonok N, Zhou H, Kufareva I, Wu B, Zhao Q, Hanson MA, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ Cell. 2016 Oct 20;167(3):750-762.e14. doi: 10.1016/j.cell.2016.10.004. PMID:27768894^[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:https://dx.doi.org/10.1016/j.febslet.2004.11.085
↑ Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Ho JH, Zvonok N, Zhou H, Kufareva I, Wu B, Zhao Q, Hanson MA, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. Crystal Structure of the Human Cannabinoid Receptor CB1. Cell. 2016 Oct 20;167(3):750-762.e14. doi: 10.1016/j.cell.2016.10.004. PMID:27768894 doi:https://dx.doi.org/10.1016/j.cell.2016.10.004

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1016/j.febslet.2004.11.085

[2] Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Ho JH, Zvonok N, Zhou H, Kufareva I, Wu B, Zhao Q, Hanson MA, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. Crystal Structure of the Human Cannabinoid Receptor CB1. Cell. 2016 Oct 20;167(3):750-762.e14. doi: 10.1016/j.cell.2016.10.004. PMID:27768894 doi:https://dx.doi.org/10.1016/j.cell.2016.10.004

[1]

[2]

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the Human Cannabinoid Receptor CB1==
-<StructureSection load='5tgz' size='340' side='right' caption='[[5tgz]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='5tgz' size='340' side='right'caption='[[5tgz]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tgz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TGZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tgz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Desulfovibrio_vulgaris_str._Hildenborough Desulfovibrio vulgaris str. Hildenborough] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TGZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TGZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZDG:4-[4-[2-(2,4-DICHLOROPHENYL)-4-METHYL-5-(PIPERIDIN-1-YLCARBAMOYL)PYRAZOL-3-YL]PHENYL]BUT-3-YNYL+NITRATE'>ZDG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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=5tgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tgz OCA], [http://pdbe.org/5tgz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tgz RCSB], [http://www.ebi.ac.uk/pdbsum/5tgz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tgz ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=ZDG:4-[4-[2-(2,4-DICHLOROPHENYL)-4-METHYL-5-(PIPERIDIN-1-YLCARBAMOYL)PYRAZOL-3-YL]PHENYL]BUT-3-YNYL+NITRATE'>ZDG</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tgz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tgz OCA], [https://pdbe.org/5tgz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tgz RCSB], [https://www.ebi.ac.uk/pdbsum/5tgz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tgz ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CNR1_HUMAN 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.<ref>PMID:15620723</ref>
+[https://www.uniprot.org/uniprot/CNR1_HUMAN 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.<ref>PMID:15620723</ref> [https://www.uniprot.org/uniprot/FLAV_NITV2 FLAV_NITV2] Low-potential electron donor to a number of redox enzymes.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Bohn, L M]]
+[[Category: Desulfovibrio vulgaris str. Hildenborough]]
-[[Category: Han, G W]]
+[[Category: Homo sapiens]]
-[[Category: Hanson, M A]]
+[[Category: Large Structures]]
-[[Category: Ho, J-H]]
+[[Category: Bohn LM]]
-[[Category: Hua, T]]
+[[Category: Han GW]]
-[[Category: Korde, A]]
+[[Category: Hanson MA]]
-[[Category: Kufareva, I]]
+[[Category: Ho JH]]
-[[Category: Laprairie, R B]]
+[[Category: Hua T]]
-[[Category: Li, S]]
+[[Category: Korde A]]
-[[Category: Liu, Z-J]]
+[[Category: Kufareva I]]
-[[Category: Makriyannis, A]]
+[[Category: Laprairie RB]]
-[[Category: Pu, M]]
+[[Category: Li S]]
-[[Category: Qu, L]]
+[[Category: Liu ZJ]]
-[[Category: Shui, W]]
+[[Category: Makriyannis A]]
-[[Category: Stahl, E L]]
+[[Category: Pu M]]
-[[Category: Stevens, R C]]
+[[Category: Qu L]]
-[[Category: Vemuri, K]]
+[[Category: Shui W]]
-[[Category: Wu, B]]
+[[Category: Stahl EL]]
-[[Category: Wu, Y]]
+[[Category: Stevens RC]]
-[[Category: Zhao, Q]]
+[[Category: Vemuri K]]
-[[Category: Zhao, S]]
+[[Category: Wu B]]
-[[Category: Zhou, H]]
+[[Category: Wu Y]]
-[[Category: Zvonok, N]]
+[[Category: Zhao Q]]
-[[Category: Cb1-flavodoxin chimera]]
+[[Category: Zhao S]]
-[[Category: G protein-coupled receptor]]
+[[Category: Zhou H]]
-[[Category: Human cannabinoid receptor cb1]]
+[[Category: Zvonok N]]
-[[Category: Lipidic cubic phase]]
-[[Category: Marijuana]]
-[[Category: Membrane protein]]
-[[Category: Signaling protein]]
-[[Category: Stabilizing antagonist am6538]]

5tgz: Difference between revisions

Latest revision as of 10:52, 30 October 2024

Crystal Structure of the Human Cannabinoid Receptor CB1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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