OCA at 16:45, 29 November 2023

OCA — Wed, 29 Nov 2023 16:45:11 GMT

←Older revision		Revision as of 16:45, 29 November 2023
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	==X-ray Crystal structure of PPARgamma R288H mutant.==		==X-ray Crystal structure of PPARgamma R288H mutant.==
-	<StructureSection load='7e2o' size='340' side='right'caption='[[7e2o]]' scene=''>	+	<StructureSection load='7e2o' size='340' side='right'caption='[[7e2o]], [[Resolution\|resolution]] 3.20Å' 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=7E2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E2O FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7e2o]] 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=7E2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E2O 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=7e2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e2o OCA], [https://pdbe.org/7e2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e2o RCSB], [https://www.ebi.ac.uk/pdbsum/7e2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e2o 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]] 3.2Å</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=7e2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e2o OCA], [https://pdbe.org/7e2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e2o RCSB], [https://www.ebi.ac.uk/pdbsum/7e2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e2o 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;">
		+	== Publication Abstract from PubMed ==
		+	Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor and the molecular target of thiazolidinedione-class antidiabetic drugs. It has been reported that the loss of function R288H mutation in the human PPARgamma ligand-binding domain (LBD) may be associated with the onset of colon cancer. A previous in vitro study showed that this mutation dampens 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2, a natural PPARgamma agonist)-dependent transcriptional activation; however, it is poorly understood why the function of the R288H mutant is impaired and what role this arginine (Arg) residue plays. In this study, we found that the apo-form of R288H PPARgamma mutant displays several altered conformational arrangements of the amino acid side chains in LBD: 1) the loss of a salt bridge between Arg288 and Glu295 leads to increased helix 3 movement; 2) closer proximity of Gln286 and His449 via a hydrogen bond, and closer proximity of Cys285 and Phe363 via hydrophobic interaction, stabilize the helix 3-helix 11 interaction; and 3) there is steric hindrance between Cys285/Gln286/Ser289/His449 and the flexible ligands 15d-PGJ2, 6-oxotetracosahexaenoic acid (6-oxoTHA), and 17-oxodocosahexaenoic acid (17-oxoDHA). These results suggest why Arg288 plays an important role in ligand binding and why the R288H mutation is disadvantageous for flexible ligand binding.
		+
		+	Structural Insights into the Loss-of-Function R288H Mutant of Human PPARgamma.,Egawa D, Ogiso T, Nishikata K, Yamamoto K, Itoh T Biol Pharm Bull. 2021;44(9):1196-1201. doi: 10.1248/bpb.b21-00253. PMID:34471047<ref>PMID:34471047</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7e2o" 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: Egawa D]]		[[Category: Egawa D]]
	[[Category: Itoh T]]		[[Category: Itoh T]]

OCA at 07:27, 19 January 2022

OCA — Wed, 19 Jan 2022 07:27:15 GMT

←Older revision		Revision as of 07:27, 19 January 2022
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-	'''Unreleased structure'''

-	~~The entry~~ 7e2o ~~is ON HOLD until Paper Publication~~	+	==X-ray Crystal structure of PPARgamma R288H mutant.==
-		+	<StructureSection load='7e2o' size='340' side='right'caption='[[7e2o]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E2O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E2O 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=7e2o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e2o OCA], [https://pdbe.org/7e2o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e2o RCSB], [https://www.ebi.ac.uk/pdbsum/7e2o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e2o ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Egawa D]]
		+	[[Category: Itoh T]]

OCA at 05:32, 24 February 2021

OCA — Wed, 24 Feb 2021 05:32:47 GMT

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

-	The entry 7e2o is ON HOLD	+	The entry 7e2o is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7e2o" [edit=sysop:move=sysop]

OCA — Wed, 17 Feb 2021 08:36:42 GMT

Protected "7e2o" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:36, 17 February 2021

OCA: New page: '''Unreleased structure''' The entry 7e2o is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 17 Feb 2021 08:36:41 GMT

New page: '''Unreleased structure''' The entry 7e2o is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7e2o is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7e2o - Revision history

OCA at 16:45, 29 November 2023

OCA at 07:27, 19 January 2022

OCA at 05:32, 24 February 2021

OCA: Protected "7e2o" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 7e2o is ON HOLD Authors: Description: Category: Unreleased Structures