5zty

From Proteopedia

(Difference between revisions)

Revision as of 08:12, 30 January 2019

Crystal structure of human G protein coupled receptor

Structural highlights

5zty is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , , , , ,
Activity:	Lysozyme, with EC number 3.2.1.17
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CNR2_HUMAN] Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 A resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257's unexpected opposing functional profile of CB2 antagonism versus CB1 agonism. Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system.

Crystal Structure of the Human Cannabinoid Receptor CB2.,Li X, Hua T, Vemuri K, Ho JH, Wu Y, Wu L, Popov P, Benchama O, Zvonok N, Locke K, Qu L, Han GW, Iyer MR, Cinar R, Coffey NJ, Wang J, Wu M, Katritch V, Zhao S, Kunos G, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ Cell. 2019 Jan 24;176(3):459-467.e13. doi: 10.1016/j.cell.2018.12.011. Epub 2019 , Jan 10. PMID:30639103^[5]

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

References

↑ Tao Q, McAllister SD, Andreassi J, Nowell KW, Cabral GA, Hurst DP, Bachtel K, Ekman MC, Reggio PH, Abood ME. Role of a conserved lysine residue in the peripheral cannabinoid receptor (CB2): evidence for subtype specificity. Mol Pharmacol. 1999 Mar;55(3):605-13. PMID:10051546
↑ Feng W, Song ZH. Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor. Biochem Pharmacol. 2003 Apr 1;65(7):1077-85. PMID:12663043
↑ Kishimoto S, Gokoh M, Oka S, Muramatsu M, Kajiwara T, Waku K, Sugiura T. 2-arachidonoylglycerol induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes through the cannabinoid CB2 receptor-dependent mechanism. J Biol Chem. 2003 Jul 4;278(27):24469-75. Epub 2003 Apr 23. PMID:12711605 doi:http://dx.doi.org/10.1074/jbc.M301359200
↑ Anand U, Otto WR, Sanchez-Herrera D, Facer P, Yiangou Y, Korchev Y, Birch R, Benham C, Bountra C, Chessell IP, Anand P. Cannabinoid receptor CB2 localisation and agonist-mediated inhibition of capsaicin responses in human sensory neurons. Pain. 2008 Sep 15;138(3):667-80. doi: 10.1016/j.pain.2008.06.007. Epub 2008 Aug, 9. PMID:18692962 doi:http://dx.doi.org/10.1016/j.pain.2008.06.007
↑ Li X, Hua T, Vemuri K, Ho JH, Wu Y, Wu L, Popov P, Benchama O, Zvonok N, Locke K, Qu L, Han GW, Iyer MR, Cinar R, Coffey NJ, Wang J, Wu M, Katritch V, Zhao S, Kunos G, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ. Crystal Structure of the Human Cannabinoid Receptor CB2. Cell. 2019 Jan 24;176(3):459-467.e13. doi: 10.1016/j.cell.2018.12.011. Epub 2019 , Jan 10. PMID:30639103 doi:http://dx.doi.org/10.1016/j.cell.2018.12.011

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/5zty"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5zty is ON HOLD  until Paper Publication
+==Crystal structure of human G protein coupled receptor==
+<StructureSection load='5zty' size='340' side='right' caption='[[5zty]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5zty]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZTY FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JU:N-(adamantan-1-yl)-1-(5-hydroxypentyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxamide'>9JU</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</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=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></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=5zty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zty OCA], [http://pdbe.org/5zty PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zty RCSB], [http://www.ebi.ac.uk/pdbsum/5zty PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zty ProSAT]</span></td></tr>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/CNR2_HUMAN CNR2_HUMAN]] Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.<ref>PMID:10051546</ref> <ref>PMID:12663043</ref> <ref>PMID:12711605</ref> <ref>PMID:18692962</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 A resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257's unexpected opposing functional profile of CB2 antagonism versus CB1 agonism. Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system.
-Authors:
+Crystal Structure of the Human Cannabinoid Receptor CB2.,Li X, Hua T, Vemuri K, Ho JH, Wu Y, Wu L, Popov P, Benchama O, Zvonok N, Locke K, Qu L, Han GW, Iyer MR, Cinar R, Coffey NJ, Wang J, Wu M, Katritch V, Zhao S, Kunos G, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ Cell. 2019 Jan 24;176(3):459-467.e13. doi: 10.1016/j.cell.2018.12.011. Epub 2019 , Jan 10. PMID:30639103<ref>PMID:30639103</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5zty" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Lysozyme]]
+[[Category: Hua, T]]
+[[Category: Li, X T]]
+[[Category: Liu, Z J]]
+[[Category: Wu, L J]]
+[[Category: Cell signaling]]
+[[Category: Gpcr]]
+[[Category: Ligand design]]
+[[Category: Membrane protein]]

5zty

From Proteopedia

Revision as of 08:12, 30 January 2019

Crystal structure of human G protein coupled receptor

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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