OCA at 10:52, 22 November 2023

OCA — Wed, 22 Nov 2023 10:52:59 GMT

←Older revision		Revision as of 10:52, 22 November 2023
Line 1:		Line 1:

	==Human PPARgamma ligand binding domain complexed with Butyrolactone 1==		==Human PPARgamma ligand binding domain complexed with Butyrolactone 1==
-	<StructureSection load='6l89' size='340' side='right'caption='[[6l89]]' scene=''>	+	<StructureSection load='6l89' size='340' side='right'caption='[[6l89]], [[Resolution\|resolution]] 2.10Å' 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=6L89 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6L89 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6l89]] 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=6L89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L89 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6l89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l89 OCA], [~~http~~://pdbe.org/6l89 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6l89 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6l89 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6l89 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]] 2.1Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=E7C:methyl+(2R)-3-(4-hydroxyphenyl)-2-[[3-(3-methylbut-2-enyl)-4-oxidanyl-phenyl]methyl]-4-oxidanyl-5-oxidanylidene-furan-2-carboxylate'>E7C</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=6l89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l89 OCA], [https://pdbe.org/6l89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l89 RCSB], [https://www.ebi.ac.uk/pdbsum/6l89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l89 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 ==
		+	Adiponectin is an adipocyte-derived cytokine having an insulin-sensitizing activity. During the phenotypic screening of secondary metabolites derived from the marine fungus Aspergillus terreus, a poly cyclin-dependent kinase (CDK) inhibitor butyrolactone I affecting CDK1 and CDK5 was discovered as a potent adiponectin production-enhancing compound in the adipogenesis model of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). CDK5 inhibitors exhibit insulin-sensitizing activities by suppressing the phosphorylation of peroxisome proliferator-activated receptor gamma (PPARgamma). However, the adiponectin production-enhancing activities of butyrolactone I have not been correlated with the potency of CDK5 inhibitor activities. In a target identification study, butyrolactone I was found to directly bind to PPARgamma. In the crystal structure of the human PPARgamma, the ligand-binding domain (LBD) in complex with butyrolactone I interacted with the amino acid residues located in the hydrophobic binding pockets of the PPARgamma LBD, which is a typical binding mode of the PPARgamma partial agonists. Therefore, the adiponectin production-enhancing effect of butyrolactone I was mediated by its polypharmacological dual modulator activities as both a CDK5 inhibitor and a PPARgamma partial agonist.
		+
		+	Cyclin-Dependent Kinase 5 Inhibitor Butyrolactone I Elicits a Partial Agonist Activity of Peroxisome Proliferator-Activated Receptor gamma.,Ahn S, Jang DM, Park SC, An S, Shin J, Han BW, Noh M Biomolecules. 2020 Feb 11;10(2). pii: biom10020275. doi: 10.3390/biom10020275. PMID:32054125<ref>PMID:32054125</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6l89" 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: Han BW]]		[[Category: Han BW]]
	[[Category: Jang DM]]		[[Category: Jang DM]]

OCA at 09:45, 16 September 2020

OCA — Wed, 16 Sep 2020 09:45:33 GMT

←Older revision		Revision as of 09:45, 16 September 2020
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-	'''Unreleased structure'''

-	~~The entry~~ 6l89 ~~is ON HOLD until Paper Publication~~	+	==Human PPARgamma ligand binding domain complexed with Butyrolactone 1==
-		+	<StructureSection load='6l89' size='340' side='right'caption='[[6l89]]' scene=''>
-	~~Authors~~: ~~Jang~~, D.M., ~~Han~~, B.W.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L89 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6L89 FirstGlance]. <br>
-	~~Description: Human PPARgamma ligand binding domain complexed with Butyrolactone 1~~	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6l89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l89 OCA], [http://pdbe.org/6l89 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l89 RCSB], [http://www.ebi.ac.uk/pdbsum/6l89 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l89 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
-	[[Category: ~~Jang, D.M~~]]	+	__TOC__
-	[[Category: ~~Han, B.W~~]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Han BW]]
		+	[[Category: Jang DM]]

OCA at 13:24, 20 November 2019

OCA — Wed, 20 Nov 2019 13:24:26 GMT

←Older revision		Revision as of 13:24, 20 November 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6l89 is ON HOLD	+	The entry 6l89 is ON HOLD until Paper Publication

	Authors: Jang, D.M., Han, B.W.		Authors: Jang, D.M., Han, B.W.

OCA: Protected "6l89" [edit=sysop:move=sysop]

OCA — Wed, 13 Nov 2019 09:16:48 GMT

Protected "6l89" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:16, 13 November 2019

OCA: New page: '''Unreleased structure''' The entry 6l89 is ON HOLD Authors: Jang, D.M., Han, B.W. Description: Human PPARgamma ligand binding domain complexed with Butyrolactone 1 [[Category: Unrele...

OCA — Wed, 13 Nov 2019 09:16:47 GMT

New page: '''Unreleased structure''' The entry 6l89 is ON HOLD Authors: Jang, D.M., Han, B.W. Description: Human PPARgamma ligand binding domain complexed with Butyrolactone 1 [[Category: Unrele...

New page

'''Unreleased structure'''

The entry 6l89 is ON HOLD

Authors: Jang, D.M., Han, B.W.

Description: Human PPARgamma ligand binding domain complexed with Butyrolactone 1
[[Category: Unreleased Structures]]
[[Category: Jang, D.M]]
[[Category: Han, B.W]]

6l89 - Revision history

OCA at 10:52, 22 November 2023

OCA at 09:45, 16 September 2020

OCA at 13:24, 20 November 2019

OCA: Protected "6l89" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6l89 is ON HOLD Authors: Jang, D.M., Han, B.W. Description: Human PPARgamma ligand binding domain complexed with Butyrolactone 1 [[Category: Unrele...