7e0a - Revision history

OCA at 16:44, 29 November 2023

OCA — Wed, 29 Nov 2023 16:44:05 GMT

←Older revision		Revision as of 16:44, 29 November 2023
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	<StructureSection load='7e0a' size='340' side='right'caption='[[7e0a]], [[Resolution\|resolution]] 1.77Å' scene=''>		<StructureSection load='7e0a' size='340' side='right'caption='[[7e0a]], [[Resolution\|resolution]] 1.77Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7e0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E0A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7e0a]] is a 1 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=7E0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E0A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EWR:(2S)-2-ethoxy-3-[4-[2-[2-methyl-5-(4-methylsulfanylphenyl)pyrrol-1-yl]ethoxy]phenyl]propanoic+acid'>EWR</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]] 1.771Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PPARG, NR1C3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EWR:(2S)-2-ethoxy-3-[4-[2-[2-methyl-5-(4-methylsulfanylphenyl)pyrrol-1-yl]ethoxy]phenyl]propanoic+acid'>EWR</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=7e0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e0a OCA], [https://pdbe.org/7e0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e0a RCSB], [https://www.ebi.ac.uk/pdbsum/7e0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e0a ProSAT]</span></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=7e0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e0a OCA], [https://pdbe.org/7e0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e0a RCSB], [https://www.ebi.ac.uk/pdbsum/7e0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e0a ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Note=Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:[https://omim.org/entry/601665 601665]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9753710</ref> Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:[https://omim.org/entry/604367 604367]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.<ref>PMID:12453919</ref> <ref>PMID:11788685</ref> Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:[https://omim.org/entry/137800 137800]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 7e0a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7e0a" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Peroxisome proliferator-activated receptor 3D structures\|Peroxisome proliferator-activated receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Honda, A]]	+	[[Category: Honda A]]
-	[[Category: Ishii, I]]	+	[[Category: Ishii I]]
-	[[Category: Kamata, S]]	+	[[Category: Kamata S]]
-	[[Category: Machida, Y]]	+	[[Category: Machida Y]]
-	[[Category: Oyama, T]]	+	[[Category: Oyama T]]
-	[[Category: Uchii, K]]	+	[[Category: Uchii K]]
-	~~[[Category: Nuclear receptor]]~~	+
-	~~[[Category: Ppar]]~~	+
-	~~[[Category: Protein-ligand complex]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 06:59, 22 September 2021

OCA — Wed, 22 Sep 2021 06:59:41 GMT

←Older revision		Revision as of 06:59, 22 September 2021
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	==X-ray structure of human PPARgamma ligand binding domain-saroglitazar co-crystals obtained by co-crystallization==		==X-ray structure of human PPARgamma ligand binding domain-saroglitazar co-crystals obtained by co-crystallization==
-	<StructureSection load='7e0a' size='340' side='right'caption='[[7e0a]]' scene=''>	+	<StructureSection load='7e0a' size='340' side='right'caption='[[7e0a]], [[Resolution\|resolution]] 1.77Å' 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=7E0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E0A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7e0a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E0A 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=7e0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e0a OCA], [https://pdbe.org/7e0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e0a RCSB], [https://www.ebi.ac.uk/pdbsum/7e0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e0a ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EWR:(2S)-2-ethoxy-3-[4-[2-[2-methyl-5-(4-methylsulfanylphenyl)pyrrol-1-yl]ethoxy]phenyl]propanoic+acid'>EWR</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PPARG, NR1C3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=7e0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e0a OCA], [https://pdbe.org/7e0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e0a RCSB], [https://www.ebi.ac.uk/pdbsum/7e0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e0a ProSAT]</span></td></tr>
	</table>		</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor-type transcription factors that consist of three subtypes (alpha, gamma, and beta/delta) with distinct functions and PPAR dual/pan agonists are expected to be the next generation of drugs for metabolic diseases. Saroglitazar is the first clinically approved PPARalpha/gamma dual agonist for treatment of diabetic dyslipidemia and is currently in clinical trials to treat non-alcoholic fatty liver disease (NAFLD); however, the structural information of its interaction with PPARalpha/gamma remains unknown. We recently revealed the high-resolution co-crystal structure of saroglitazar and the PPARalpha-ligand binding domain (LBD) through X-ray crystallography, and in this study, we report the structure of saroglitazar and the PPARgamma-LBD. Saroglitazar was located at the center of "Y"-shaped PPARgamma-ligand-binding pocket (LBP), just as it was in the respective region of PPARalpha-LBP. Its carboxylic acid was attached to four amino acids (Ser289/His323/His449/Thr473), which contributes to the stabilization of Activating Function-2 helix 12, and its phenylpyrrole moiety was rotated 121.8 degrees in PPARgamma-LBD from that in PPARalpha-LBD to interact with Phe264. PPARdelta-LBD has the consensus four amino acids (Thr253/His287/His413/Tyr437) towards the carboxylic acids of its ligands, but it seems to lack sufficient space to accept saroglitazar because of the steric hindrance between the Trp228 or Arg248 residue of PPARdelta-LBD and its methylthiophenyl moiety. Accordingly, in a coactivator recruitment assay, saroglitazar activated PPARalpha-LBD and PPARgamma-LBD but not PPARdelta-LBD, whereas glycine substitution of either Trp228, Arg248, or both of PPARdelta-LBD conferred saroglitazar concentration-dependent activation. Our findings may be valuable in the molecular design of PPARalpha/gamma dual or PPARalpha/gamma/delta pan agonists.
		+
		+	Structural Basis for Anti-non-alcoholic Fatty Liver Disease and Diabetic Dyslipidemia Drug Saroglitazar as a PPAR alpha/gamma Dual Agonist.,Honda A, Kamata S, Satta C, Machida Y, Uchii K, Terasawa K, Nemoto A, Oyama T, Ishii I Biol Pharm Bull. 2021;44(9):1210-1219. doi: 10.1248/bpb.b21-00232. PMID:34471049<ref>PMID:34471049</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7e0a" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Honda A]]	+	[[Category: Honda, A]]
-	[[Category: Ishii I]]	+	[[Category: Ishii, I]]
-	[[Category: Kamata S]]	+	[[Category: Kamata, S]]
-	[[Category: Machida Y]]	+	[[Category: Machida, Y]]
-	[[Category: Oyama T]]	+	[[Category: Oyama, T]]
-	[[Category: Uchii K]]	+	[[Category: Uchii, K]]
		+	[[Category: Nuclear receptor]]
		+	[[Category: Ppar]]
		+	[[Category: Protein-ligand complex]]
		+	[[Category: Transcription]]

OCA at 08:56, 8 September 2021

OCA — Wed, 08 Sep 2021 08:56:39 GMT

←Older revision		Revision as of 08:56, 8 September 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7e0a is ~~ON HOLD until Paper Publication~~	+	==X-ray structure of human PPARgamma ligand binding domain-saroglitazar co-crystals obtained by co-crystallization==
-		+	<StructureSection load='7e0a' size='340' side='right'caption='[[7e0a]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E0A FirstGlance]. <br>
-	~~Description~~:	+	</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=7e0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e0a OCA], [https://pdbe.org/7e0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e0a RCSB], [https://www.ebi.ac.uk/pdbsum/7e0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e0a ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Honda A]]
		+	[[Category: Ishii I]]
		+	[[Category: Kamata S]]
		+	[[Category: Machida Y]]
		+	[[Category: Oyama T]]
		+	[[Category: Uchii K]]

OCA at 05:32, 24 February 2021

OCA — Wed, 24 Feb 2021 05:32:09 GMT

←Older revision		Revision as of 05:32, 24 February 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7e0a is ON HOLD	+	The entry 7e0a is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7e0a" [edit=sysop:move=sysop]

OCA — Wed, 03 Feb 2021 09:22:13 GMT

Protected "7e0a" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:22, 3 February 2021

OCA: New page: '''Unreleased structure''' The entry 7e0a is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 03 Feb 2021 09:22:12 GMT

New page: '''Unreleased structure''' The entry 7e0a is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7e0a is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]