6dgo - Revision history

OCA at 06:05, 11 October 2023

2023-10-11T06:05:50Z

←Older revision		Revision as of 06:05, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6dgo' size='340' side='right'caption='[[6dgo]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='6dgo' size='340' side='right'caption='[[6dgo]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6dgo]] 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=6DGO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6DGO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6dgo]] 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=6DGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DGO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GD4:(5S)-5-[(4-{[(2R)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl]methoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione'>GD4</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]] 3.1Å</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=GD4:(5S)-5-[(4-{[(2R)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl]methoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione'>GD4</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=6dgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dgo OCA], [~~http~~://pdbe.org/6dgo PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6dgo RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6dgo PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6dgo 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=6dgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dgo OCA], [https://pdbe.org/6dgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dgo RCSB], [https://www.ebi.ac.uk/pdbsum/6dgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dgo 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 ==
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	==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-transcription inhibitor complex]]~~	+
-	~~[[Category: Tzd~~]]	+

OCA at 12:52, 25 December 2019

2019-12-25T12:52:59Z

←Older revision		Revision as of 12:52, 25 December 2019
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6dgo" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6dgo" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phenylethanolamine N-methyltransferase 3D structures\|Phenylethanolamine N-methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:46, 6 November 2019

2019-11-06T07:46:38Z

←Older revision		Revision as of 07:46, 6 November 2019
Line 3:		Line 3:
	<StructureSection load='6dgo' size='340' side='right'caption='[[6dgo]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='6dgo' size='340' side='right'caption='[[6dgo]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6dgo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DGO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DGO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6dgo]] 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=6DGO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DGO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GD4:(5S)-5-[(4-{[(2R)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl]methoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione'>GD4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GD4:(5S)-5-[(4-{[(2R)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl]methoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione'>GD4</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=6dgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dgo OCA], [http://pdbe.org/6dgo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dgo RCSB], [http://www.ebi.ac.uk/pdbsum/6dgo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dgo 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=6dgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dgo OCA], [http://pdbe.org/6dgo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dgo RCSB], [http://www.ebi.ac.uk/pdbsum/6dgo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dgo 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 ==
		+	Ligand-receptor interactions, which are ubiquitous in physiology, are described by theoretical models of receptor pharmacology. Structural evidence for graded efficacy receptor conformations predicted by receptor theory has been limited but is critical to fully validate theoretical models. We applied quantitative structure-function approaches to characterize the effects of structurally similar and structurally diverse agonists on the conformational ensemble of nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). For all ligands, agonist functional efficacy is correlated to a shift in the conformational ensemble equilibrium from a ground state toward an active state, which is detected by NMR spectroscopy but not observed in crystal structures. For the structurally similar ligands, ligand potency and affinity are also correlated to efficacy and conformation, indicating ligand residence times among related analogs may influence receptor conformation and function. Our results derived from quantitative graded activity-conformation correlations provide experimental evidence and a platform with which to extend and test theoretical models of receptor pharmacology to more accurately describe and predict ligand-dependent receptor activity.
		+
		+	Quantitative structural assessment of graded receptor agonism.,Shang J, Brust R, Griffin PR, Kamenecka TM, Kojetin DJ Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22179-22188. doi:, 10.1073/pnas.1909016116. Epub 2019 Oct 14. PMID:31611383<ref>PMID:31611383</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6dgo" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Kojetin, D J]]		[[Category: Kojetin, D J]]

OCA at 06:43, 23 May 2019

2019-05-23T06:43:13Z

←Older revision		Revision as of 06:43, 23 May 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6dgo is ~~ON HOLD until Paper Publication~~	+	==Crystal Structure of Human PPARgamma Ligand Binding Domain in Complex with Troglitazone==
-		+	<StructureSection load='6dgo' size='340' side='right'caption='[[6dgo]], [[Resolution\|resolution]] 3.10Å' scene=''>
-	~~Authors~~: ~~Shang~~, J., ~~Kojetin~~, D.J.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6dgo]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DGO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DGO FirstGlance]. <br>
-	~~Description~~: ~~Crystal Structure~~ of ~~Human PPARgamma Ligand Binding Domain~~ in ~~Complex~~ with ~~Troglitazone~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GD4:(5S)-5-[(4-{[(2R)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl]methoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione'>GD4</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=6dgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dgo OCA], [http://pdbe.org/6dgo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dgo RCSB], [http://www.ebi.ac.uk/pdbsum/6dgo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dgo 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: Large Structures]]
		+	[[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-transcription inhibitor complex]]
		+	[[Category: Tzd]]

OCA at 04:18, 6 June 2018

2018-06-06T04:18:02Z

←Older revision		Revision as of 04:18, 6 June 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

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

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

2018-05-23T06:06:13Z

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

←Older revision

Revision as of 06:06, 23 May 2018

OCA: New page: '''Unreleased structure''' The entry 6dgo is ON HOLD Authors: Shang, J., Kojetin, D.J. Description: Crystal Structure of Human PPARgamma Ligand Binding Domain in Complex with Troglitaz...

2018-05-23T06:06:12Z

New page: '''Unreleased structure''' The entry 6dgo is ON HOLD Authors: Shang, J., Kojetin, D.J. Description: Crystal Structure of Human PPARgamma Ligand Binding Domain in Complex with Troglitaz...

New page

'''Unreleased structure'''

The entry 6dgo is ON HOLD

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

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