OCA at 15:57, 29 November 2023

OCA — Wed, 29 Nov 2023 15:57:58 GMT

←Older revision		Revision as of 15:57, 29 November 2023
Line 1:		Line 1:

-	====	+	==Novel natural PPARalpha agonist with a unique binding mode==
-	<StructureSection load='7c6q' size='340' side='right'caption='[[7c6q]]' scene=''>	+	<StructureSection load='7c6q' size='340' side='right'caption='[[7c6q]], [[Resolution\|resolution]] 2.76Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7c6q]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7C6Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C6Q FirstGlance]. <br>
-	</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=7c6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c6q OCA], [https://pdbe.org/7c6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c6q RCSB], [https://www.ebi.ac.uk/pdbsum/7c6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c6q ProSAT]</span></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]] 2.76Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAU:13-METHYL[1,3]BENZODIOXOLO[5,6-C][1,3]DIOXOLO[4,5-I]PHENANTHRIDIN-13-IUM'>SAU</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=7c6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c6q OCA], [https://pdbe.org/7c6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c6q RCSB], [https://www.ebi.ac.uk/pdbsum/7c6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c6q ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PPARA_HUMAN PPARA_HUMAN] Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.<ref>PMID:7684926</ref> <ref>PMID:7629123</ref> <ref>PMID:9556573</ref> <ref>PMID:10195690</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Peroxisome proliferator-activated receptors (PPARs) play crucial roles in glucose and lipid metabolism and inflammation. Sanguinarine is a natural product that is isolated from Sanguinaria Canadensis, a potential therapeutic agent for intervention in chronic diseases. In this study, biochemical and cell-based promoter-reporter gene assays revealed that sanguinarine activated both PPARalpha and PPARgamma, and enhanced their transcriptional activity; thus, sanguinarine was identified as a dual agonist of PPARalpha/gamma. Similar to fenofibrate, sanguinarine upregulates the expression of PPARalpha-target genes in hepatocytes. Sanguinarine also modulates the expression of key PPARgamma-target genes and promotes adipocyte differentiation, but with a lower adipogenic activity compared with rosiglitazone. We report the crystal structure of sanguinarine bound to PPARalpha, which reveals a unique ligand-binding mode of sanguinarine, dissimilar to the classic Y-shaped binding pocket, which may represent a new pharmacophore that can be optimized for selectively targeting PPARalpha. Further structural and functional studies uncover the molecular basis for the selectivity of sanguinarine toward PPARalpha/gamma among all three PPARs. In summary, our study identifies a PPARalpha/gamma dual agonist with a unique ligand-binding mode, and provides a promising and viable novel template for the design of dual-targeting PPARs ligands.
		+
		+	Structural Basis for PPARs Activation by The Dual PPARalpha/gamma Agonist Sanguinarine: A Unique Mode of Ligand Recognition.,Tian S, Wang R, Chen S, He J, Zheng W, Li Y Molecules. 2021 Oct 3;26(19):6012. doi: 10.3390/molecules26196012. PMID:34641558<ref>PMID:34641558</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7c6q" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Peroxisome proliferator-activated receptor 3D structures\|Peroxisome proliferator-activated receptor 3D structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Li Y]]
		+	[[Category: Tian SY]]
		+	[[Category: Wang R]]
		+	[[Category: Zheng WL]]

OCA at 09:18, 26 May 2021

OCA — Wed, 26 May 2021 09:18:39 GMT

←Older revision		Revision as of 09:18, 26 May 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7c6q ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='7c6q' size='340' side='right'caption='[[7c6q]]' scene=''>
-	~~Authors~~: ~~Tian, S~~.Y.~~, Wang, R~~.~~, Zheng, W~~.L.~~, Li, Y~~.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description~~: ~~Novel natural PPARalpha agonist with a unique binding mode~~	+	</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=7c6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c6q OCA], [https://pdbe.org/7c6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c6q RCSB], [https://www.ebi.ac.uk/pdbsum/7c6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c6q ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[~~[Category~~: ~~Zheng, W~~.L]]	+	__TOC__
-	[~~[Category~~: ~~Li, Y~~]]	+	</StructureSection>
-	[[Category: ~~Wang, R~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Tian, S.Y~~]]	+	[[Category: Z-disk]]

OCA at 05:16, 10 June 2020

OCA — Wed, 10 Jun 2020 05:16:41 GMT

←Older revision		Revision as of 05:16, 10 June 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7c6q is ON HOLD	+	The entry 7c6q is ON HOLD until Paper Publication

	Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y.		Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y.

OCA: Protected "7c6q" [edit=sysop:move=sysop]

OCA — Wed, 27 May 2020 05:20:35 GMT

Protected "7c6q" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:20, 27 May 2020

OCA: New page: '''Unreleased structure''' The entry 7c6q is ON HOLD Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y. Description: Novel natural PPARalpha agonist with a unique binding mode [[Catego...

OCA — Wed, 27 May 2020 05:20:33 GMT

New page: '''Unreleased structure''' The entry 7c6q is ON HOLD Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y. Description: Novel natural PPARalpha agonist with a unique binding mode [[Catego...

New page

'''Unreleased structure'''

The entry 7c6q is ON HOLD

Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y.

Description: Novel natural PPARalpha agonist with a unique binding mode
[[Category: Unreleased Structures]]
[[Category: Zheng, W.L]]
[[Category: Li, Y]]
[[Category: Wang, R]]
[[Category: Tian, S.Y]]

7c6q - Revision history

OCA at 15:57, 29 November 2023

OCA at 09:18, 26 May 2021

OCA at 05:16, 10 June 2020

OCA: Protected "7c6q" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7c6q is ON HOLD Authors: Tian, S.Y., Wang, R., Zheng, W.L., Li, Y. Description: Novel natural PPARalpha agonist with a unique binding mode [[Catego...