6vzl - Revision history

OCA at 08:22, 11 October 2023

OCA — Wed, 11 Oct 2023 08:22:54 GMT

←Older revision		Revision as of 08:22, 11 October 2023
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	<StructureSection load='6vzl' size='340' side='right'caption='[[6vzl]], [[Resolution\|resolution]] 2.07Å' scene=''>		<StructureSection load='6vzl' size='340' side='right'caption='[[6vzl]], [[Resolution\|resolution]] 2.07Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6vzl]] is a 2 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=6VZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VZL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vzl]] 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=6VZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VZL FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDK:(2~{S})-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]-2-[[2-(phenylcarbonyl)phenyl]amino]propanoic+acid'>EDK</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]] 2.07Å</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=EDK:(2~{S})-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]-2-[[2-(phenylcarbonyl)phenyl]amino]propanoic+acid'>EDK</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=6vzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vzl OCA], [https://pdbe.org/6vzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vzl RCSB], [https://www.ebi.ac.uk/pdbsum/6vzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vzl 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=6vzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vzl OCA], [https://pdbe.org/6vzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vzl RCSB], [https://www.ebi.ac.uk/pdbsum/6vzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vzl ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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.	+	[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 ==		== 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>	+	[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 6vzl" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6vzl" 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: Kojetin~~, D J~~]]	+	[[Category: Kojetin DJ]]
-	[[Category: Shang, J]]	+	[[Category: Shang J]]
-	~~[[Category: Drug design]]~~	+
-	~~[[Category: Nuclear receptor]]~~	+
-	~~[[Category: Therapeutic target]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Tzd~~]]	+

OCA at 08:55, 29 September 2021

OCA — Wed, 29 Sep 2021 08:55:02 GMT

←Older revision		Revision as of 08:55, 29 September 2021
Line 1:		Line 1:

	==Crystal structure of human PPARgamma ligand binding domain in complex with GW1929==		==Crystal structure of human PPARgamma ligand binding domain in complex with GW1929==
-	<StructureSection load='6vzl' size='340' side='right'caption='[[6vzl]]' scene=''>	+	<StructureSection load='6vzl' size='340' side='right'caption='[[6vzl]], [[Resolution\|resolution]] 2.07Å' 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=6VZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VZL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6vzl]] is a 2 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=6VZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VZL 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=6vzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vzl OCA], [https://pdbe.org/6vzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vzl RCSB], [https://www.ebi.ac.uk/pdbsum/6vzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vzl 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=EDK:(2~{S})-3-[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]-2-[[2-(phenylcarbonyl)phenyl]amino]propanoic+acid'>EDK</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=6vzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vzl OCA], [https://pdbe.org/6vzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vzl RCSB], [https://www.ebi.ac.uk/pdbsum/6vzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vzl 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 ==
		+	Ligands bind to an occluded orthosteric ligand-binding pocket within the nuclear receptor ligand-binding domain. Molecular simulations have revealed theoretical ligand entry/exit pathways to the orthosteric pocket; however, it remains unclear whether ligand binding proceeds through induced fit or conformational selection mechanisms. Here, using nuclear magnetic resonance spectroscopy, isothermal titration calorimetry, and surface plasmon resonance analysis, we provide evidence that structurally distinct agonists bind peroxisome proliferator-activated receptor gamma (PPARgamma) via a two-step induced fit mechanism involving an initial fast kinetic step followed by a slow conformational change. The agonist encounter complex binding pose is suggested in crystal structures where ligands bind to a surface pore suggested as a ligand entry site in molecular simulations. Our findings suggest an activation mechanism for PPARgamma whereby agonist binding occurs through an initial encounter complex followed by a transition of the ligand into the final binding pose within the orthosteric pocket, inducing a transcriptionally active conformation.
		+
		+	Structural mechanism underlying ligand binding and activation of PPARgamma.,Shang J, Kojetin DJ Structure. 2021 Sep 2;29(9):940-950.e4. doi: 10.1016/j.str.2021.02.006. Epub 2021, Mar 12. PMID:33713599<ref>PMID:33713599</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6vzl" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Kojetin DJ]]	+	[[Category: Kojetin, D J]]
-	[[Category: Shang J]]	+	[[Category: Shang, J]]
		+	[[Category: Drug design]]
		+	[[Category: Nuclear receptor]]
		+	[[Category: Therapeutic target]]
		+	[[Category: Transcription]]
		+	[[Category: Tzd]]

OCA at 14:41, 3 March 2021

OCA — Wed, 03 Mar 2021 14:41:35 GMT

←Older revision		Revision as of 14:41, 3 March 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6vzl ~~is ON HOLD until Paper Publication~~	+	==Crystal structure of human PPARgamma ligand binding domain in complex with GW1929==
-		+	<StructureSection load='6vzl' size='340' side='right'caption='[[6vzl]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VZL 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=6vzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vzl OCA], [https://pdbe.org/6vzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vzl RCSB], [https://www.ebi.ac.uk/pdbsum/6vzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vzl ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Kojetin DJ]]
		+	[[Category: Shang J]]

OCA at 03:55, 13 May 2020

OCA — Wed, 13 May 2020 03:55:49 GMT

←Older revision		Revision as of 03:55, 13 May 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 11 Mar 2020 06:05:37 GMT

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

←Older revision

Revision as of 06:05, 11 March 2020

OCA: New page: '''Unreleased structure''' The entry 6vzl is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 11 Mar 2020 06:05:36 GMT

New page: '''Unreleased structure''' The entry 6vzl is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6vzl is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]