6aug - Revision history

OCA at 14:25, 4 October 2023

2023-10-04T14:25:16Z

←Older revision		Revision as of 14:25, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='6aug' size='340' side='right'caption='[[6aug]], [[Resolution\|resolution]] 2.73Å' scene=''>		<StructureSection load='6aug' size='340' side='right'caption='[[6aug]], [[Resolution\|resolution]] 2.73Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aug]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AUG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aug]] 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=6AUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AUG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BXG:2-chloro-N-(6-methoxyquinolin-4-yl)-5-nitrobenzamide'>BXG</scene>, <scene name='pdbligand=KNA:NONANOIC+ACID'>KNA</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]] 2.73Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PPARG, NR1C3 ([http://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=BXG:2-chloro-N-(6-methoxyquinolin-4-yl)-5-nitrobenzamide'>BXG</scene>, <scene name='pdbligand=KNA:NONANOIC+ACID'>KNA</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aug OCA], [~~http~~://pdbe.org/6aug PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6aug RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6aug PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6aug 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=6aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aug OCA], [https://pdbe.org/6aug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aug RCSB], [https://www.ebi.ac.uk/pdbsum/6aug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aug ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://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:[~~http~~://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:[~~http~~://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:[~~http~~://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 ==
-	[~~[http~~://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 ==
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[~~Phenylethanolamine N~~-~~methyltransferase~~ 3D structures\|~~Phenylethanolamine N~~-~~methyltransferase~~ 3D structures]]	+	*[[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 12:45, 25 December 2019

2019-12-25T12:45:07Z

←Older revision

Revision as of 12:45, 25 December 2019

OCA at 06:44, 9 January 2019

2019-01-09T06:44:34Z

←Older revision		Revision as of 06:44, 9 January 2019
Line 3:		Line 3:
	<StructureSection load='6aug' size='340' side='right' caption='[[6aug]], [[Resolution\|resolution]] 2.73Å' scene=''>		<StructureSection load='6aug' size='340' side='right' caption='[[6aug]], [[Resolution\|resolution]] 2.73Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6aug]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AUG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6aug]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AUG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BXG:2-chloro-N-(6-methoxyquinolin-4-yl)-5-nitrobenzamide'>BXG</scene>, <scene name='pdbligand=KNA:NONANOIC+ACID'>KNA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BXG:2-chloro-N-(6-methoxyquinolin-4-yl)-5-nitrobenzamide'>BXG</scene>, <scene name='pdbligand=KNA:NONANOIC+ACID'>KNA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PPARG, NR1C3 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aug OCA], [http://pdbe.org/6aug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aug RCSB], [http://www.ebi.ac.uk/pdbsum/6aug PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aug ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aug OCA], [http://pdbe.org/6aug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aug RCSB], [http://www.ebi.ac.uk/pdbsum/6aug PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aug ProSAT]</span></td></tr>
	</table>		</table>
Line 11:		Line 12:
	== Function ==		== Function ==
	[[http://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>		[[http://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 ==
		+	Crystal structures of peroxisome proliferator-activated receptor gamma (PPARgamma) have revealed overlapping binding modes for synthetic and natural/endogenous ligands, indicating competition for the orthosteric pocket. Here we show that cobinding of a synthetic ligand to the orthosteric pocket can push natural and endogenous PPARgamma ligands (fatty acids) out of the orthosteric pocket towards an alternate ligand-binding site near the functionally important omega (Omega)-loop. X-ray crystallography, NMR spectroscopy, all-atom molecular dynamics simulations, and mutagenesis coupled to quantitative biochemical functional and cellular assays reveal that synthetic ligand and fatty acid cobinding can form a 'ligand link' to the Omega-loop and synergistically affect the structure and function of PPARgamma. These findings contribute to a growing body of evidence indicating ligand binding to nuclear receptors can be more complex than the classical one-for-one orthosteric exchange of a natural or endogenous ligand with a synthetic ligand.
		+
		+	Cooperative cobinding of synthetic and natural ligands to the nuclear receptor PPARgamma.,Shang J, Brust R, Mosure SA, Bass J, Munoz-Tello P, Lin H, Hughes TS, Tang M, Ge Q, Kamenekca TM, Kojetin DJ Elife. 2018 Dec 21;7. pii: 43320. doi: 10.7554/eLife.43320. PMID:30575522<ref>PMID:30575522</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6aug" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Kojetin, D J]]		[[Category: Kojetin, D J]]
	[[Category: Shang, J]]		[[Category: Shang, J]]

OCA at 07:30, 12 September 2018

2018-09-12T07:30:53Z

←Older revision		Revision as of 07:30, 12 September 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6aug is ~~ON HOLD until Paper Publication~~	+	==Crystal Structure of Human PPARgamma Ligand Binding Domain in Complex with SR16832==
-		+	<StructureSection load='6aug' size='340' side='right' caption='[[6aug]], [[Resolution\|resolution]] 2.73Å' scene=''>
-	~~Authors~~: ~~Shang~~, J., ~~Kojetin~~, D.J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6aug]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AUG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AUG FirstGlance]. <br>
-	~~Description~~: ~~Crystal Structure~~ of ~~Human PPARgamma Ligand Binding Domain~~ in ~~Complex~~ with ~~SR16832~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BXG:2-chloro-N-(6-methoxyquinolin-4-yl)-5-nitrobenzamide'>BXG</scene>, <scene name='pdbligand=KNA:NONANOIC+ACID'>KNA</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6aug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aug OCA], [http://pdbe.org/6aug PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aug RCSB], [http://www.ebi.ac.uk/pdbsum/6aug PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aug ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://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:[http://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:[http://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:[http://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 ==
		+	[[http://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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Kojetin, D J]]
	[[Category: Shang, J]]		[[Category: Shang, J]]
-	[[Category: ~~Kojetin, D.J~~]]	+	[[Category: Drug design]]
		+	[[Category: Nuclear receptor]]
		+	[[Category: Therapeutic target]]
		+	[[Category: Transcription]]
		+	[[Category: Tzd]]

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

2017-09-27T16:48:24Z

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

←Older revision

Revision as of 16:48, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6aug is ON HOLD until Paper Publication Authors: Shang, J., Kojetin, D.J. Description: Crystal Structure of Human PPARgamma Ligand Binding Domain i...

2017-09-27T16:48:23Z

New page: '''Unreleased structure''' The entry 6aug is ON HOLD until Paper Publication Authors: Shang, J., Kojetin, D.J. Description: Crystal Structure of Human PPARgamma Ligand Binding Domain i...

New page

'''Unreleased structure'''

The entry 6aug is ON HOLD until Paper Publication

Authors: Shang, J., Kojetin, D.J.

Description: Crystal Structure of Human PPARgamma Ligand Binding Domain in Complex with SR16832
[[Category: Unreleased Structures]]
[[Category: Shang, J]]
[[Category: Kojetin, D.J]]