OCA at 06:25, 6 September 2023

OCA — Wed, 06 Sep 2023 06:25:55 GMT

←Older revision		Revision as of 06:25, 6 September 2023
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-	'''Unreleased structure'''

-	~~The entry~~ 8jim is ~~ON HOLD until Paper~~ Publication	+	==Cryo-EM structure of MMF bound ketone body receptor HCAR2-Gi signaling complex==
		+	<StructureSection load='8jim' size='340' side='right'caption='[[8jim]], [[Resolution\|resolution]] 2.98Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8jim]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8JIM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JIM FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.98Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AW9:(2Z)-4-methoxy-4-oxobut-2-enoic+acid'>AW9</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=8jim FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jim OCA], [https://pdbe.org/8jim PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jim RCSB], [https://www.ebi.ac.uk/pdbsum/8jim PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jim ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/GBB1_HUMAN GBB1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.<ref>PMID:18611381</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Hydroxycarboxylic acid receptor 2 (HCAR2), modulated by endogenous ketone body beta-hydroxybutyrate and exogenous niacin, is a promising therapeutic target for inflammation-related diseases. HCAR2 mediates distinct pathophysiological events by activating G(i/o) protein or beta-arrestin effectors. Here, we characterize compound 9n as a G(i)-biased allosteric modulator (BAM) of HCAR2 and exhibit anti-inflammatory efficacy in RAW264.7 macrophages via a specific HCAR2-G(i) pathway. Furthermore, four structures of HCAR2-G(i) complex bound to orthosteric agonists (niacin or monomethyl fumarate), compound 9n, and niacin together with compound 9n simultaneously reveal a common orthosteric site and a unique allosteric site. Combined with functional studies, we decipher the action framework of biased allosteric modulation of compound 9n on the orthosteric site. Moreover, co-administration of compound 9n with orthosteric agonists could enhance anti-inflammatory effects in the mouse model of colitis. Together, our study provides insight to understand the molecular pharmacology of the BAM and facilitates exploring the therapeutic potential of the BAM with orthosteric drugs.

-	~~Authors~~:	+	Biased allosteric activation of ketone body receptor HCAR2 suppresses inflammation.,Zhao C, Wang H, Liu Y, Cheng L, Wang B, Tian X, Fu H, Wu C, Li Z, Shen C, Yu J, Yang S, Hu H, Fu P, Ma L, Wang C, Yan W, Shao Z Mol Cell. 2023 Aug 11:S1097-2765(23)00605-6. doi: 10.1016/j.molcel.2023.07.030. PMID:37597514<ref>PMID:37597514</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8jim" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Mus musculus]]
		+	[[Category: Cheng L]]
		+	[[Category: Liu Y]]
		+	[[Category: Shao ZH]]
		+	[[Category: Tian XW]]
		+	[[Category: Yan W]]
		+	[[Category: Zhao C]]

OCA at 19:41, 28 June 2023

OCA — Wed, 28 Jun 2023 19:41:06 GMT

←Older revision		Revision as of 19:41, 28 June 2023
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8jim is ON HOLD	+	The entry 8jim is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8jim" [edit=sysop:move=sysop]

OCA — Wed, 07 Jun 2023 04:14:24 GMT

Protected "8jim" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:14, 7 June 2023

OCA: New page: '''Unreleased structure''' The entry 8jim is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 07 Jun 2023 04:14:23 GMT

New page: '''Unreleased structure''' The entry 8jim is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8jim is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8jim - Revision history

OCA at 06:25, 6 September 2023

OCA at 19:41, 28 June 2023

OCA: Protected "8jim" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8jim is ON HOLD Authors: Description: Category: Unreleased Structures