5two - Revision history

OCA at 13:15, 4 October 2023

2023-10-04T13:15:02Z

← Older revision		Revision as of 13:15, 4 October 2023
Line 1:		Line 1:

	==Peroxisome proliferator-activated receptor gamma ligand binding domain in complex with a novel selectively PPAR gamma-modulating ligand VSP-51==		==Peroxisome proliferator-activated receptor gamma ligand binding domain in complex with a novel selectively PPAR gamma-modulating ligand VSP-51==
	<StructureSection load='5two' size='340' side='right' caption='[[5two]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='5two' size='340' side='right'caption='[[5two]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5two]] 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=5TWO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5TWO FirstGlance]. <br>		<table><tr><td colspan='2'>[[5two]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Unidentified Unidentified]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TWO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TWO FirstGlance]. <br>
	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=7MV:N-BENZYL-1~~-[~~(4-CHLORO-3-FLUOROPHENYL)METHYL~~]~~-1H-INDOLE-5-CARBOXAMIDE'>7MV</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]] 1.927Å</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=7MV:N-BENZYL-1-[(4-CHLORO-3-FLUOROPHENYL)METHYL]-1H-INDOLE-5-CARBOXAMIDE'>7MV</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=5two FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5two OCA], [~~http~~://pdbe.org/5two PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5two RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5two PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5two 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=5two FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5two OCA], [https://pdbe.org/5two PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5two RCSB], [https://www.ebi.ac.uk/pdbsum/5two PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5two 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==
	*[[Peroxisome ~~Proliferator~~-~~Activated Receptors~~\|Peroxisome ~~Proliferator~~-~~Activated Receptors~~]]		*[[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: ~~Melcher, K~~]]		[[Category: Large Structures]]
	[[Category: ~~Shi, J~~]]		[[Category: Unidentified]]
	[[Category: ~~Suino-Powell,~~ K]]		[[Category: Melcher K]]
	[[Category: ~~Xu, H E~~]]		[[Category: Shi J]]
	[[Category: ~~Yi, W~~]]		[[Category: Suino-Powell K]]
	[[Category: ~~Zhao, G~~]]		[[Category: Xu HE]]
	[[Category: ~~Zhou, X E~~]]		[[Category: Yi W]]
	[[Category: ~~Dna binding protein~~]]		[[Category: Zhao G]]
	[[Category: ~~Lignad binding domain]]~~		[[Category: Zhou XE]]
	~~[[Category: Peroxisome proliferator-activated receptor gamma]]~~
	~~[[Category: Selective ppar gamma ligand]]~~
	~~[[Category: Transcription]]~~
	~~[[Category: Vsp-51~~]]

OCA at 06:35, 24 October 2018

2018-10-24T06:35:02Z

← Older revision		Revision as of 06:35, 24 October 2018
Line 1:		Line 1:

	==Peroxisome proliferator-activated receptor gamma ~~lignad~~ binding domain in complex with a novel selectively PPAR gamma-modulating ligand VSP-51==		==Peroxisome proliferator-activated receptor gamma ligand binding domain in complex with a novel selectively PPAR gamma-modulating ligand VSP-51==
	<StructureSection load='5two' size='340' side='right' caption='[[5two]], [[Resolution\|resolution]] 1.93Å' scene=''>		<StructureSection load='5two' size='340' side='right' caption='[[5two]], [[Resolution\|resolution]] 1.93Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5two]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TWO FirstGlance]. <br>		<table><tr><td colspan='2'>[[5two]] 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=5TWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TWO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7MV:N-BENZYL-1-[(4-CHLORO-3-FLUOROPHENYL)METHYL]-1H-INDOLE-5-CARBOXAMIDE'>7MV</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7MV:N-BENZYL-1-[(4-CHLORO-3-FLUOROPHENYL)METHYL]-1H-INDOLE-5-CARBOXAMIDE'>7MV</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=5two FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5two OCA], [http://pdbe.org/5two PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5two RCSB], [http://www.ebi.ac.uk/pdbsum/5two PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5two 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=5two FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5two OCA], [http://pdbe.org/5two PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5two RCSB], [http://www.ebi.ac.uk/pdbsum/5two PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5two ProSAT]</span></td></tr>
	</table>		</table>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5two" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5two" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Peroxisome Proliferator-Activated Receptors\|Peroxisome Proliferator-Activated Receptors]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Human]]
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
	[[Category: Shi, J]]		[[Category: Shi, J]]

OCA at 09:28, 10 March 2017

2017-03-10T09:28:58Z

← Older revision		Revision as of 09:28, 10 March 2017
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The~~ entry ~~5two~~ is ~~ON HOLD~~ ~~until Paper~~ Publication		==Peroxisome proliferator-activated receptor gamma lignad binding domain in complex with a novel selectively PPAR gamma-modulating ligand VSP-51==
			<StructureSection load='5two' size='340' side='right' caption='[[5two]], [[Resolution\|resolution]] 1.93Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[5two]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TWO FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7MV:N-BENZYL-1-[(4-CHLORO-3-FLUOROPHENYL)METHYL]-1H-INDOLE-5-CARBOXAMIDE'>7MV</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=5two FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5two OCA], [http://pdbe.org/5two PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5two RCSB], [http://www.ebi.ac.uk/pdbsum/5two PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5two 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>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Thiazolidinediones (TZD) function as potent anti-diabetic drugs through their direct action on the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma), but their therapeutic benefits are compromised by severe side effects. To address this concern, here we developed a potent "hit" compound, VSP-51, which is a novel selective PPARgamma-modulating ligand with improved therapeutic profiles in vitro compared to the multi-billion dollar TZD drug rosiglitazone (Rosi). Unlike Rosi, VSP-51 is a partial agonist of PPARgamma with improved insulin sensitivity due to its ability to bind PPARgamma with high affinity without stimulating adipocyte differentiation and the expression of adipogenesis-related genes. We have determined the crystal structure of the PPARgamma ligand-binding domain (LBD) in complex with VSP-51, which revealed a unique mode of binding for VSP-51 and provides the molecular basis for the discrimination between VSP-51 from TZDs and other ligands such as telmisartan, SR1663 and SR1664. Taken together, our findings demonstrate that: a) VSP-51 can serve as a promising candidate for anti-diabetic drug discovery; and b) provide a rational basis for the development of future pharmacological agents targeting PPARgamma with advantages over current TZD drugs.

	~~Authors:~~ Yi, W., Shi, J., Zhao, G., Zhou~~, X.E.~~, Suino-Powell, K., Melcher, K., Xu~~, H~~.E.		Identification of a novel selective PPARgamma ligand with a unique binding mode and improved therapeutic profile in vitro.,Yi W, Shi J, Zhao G, Zhou XE, Suino-Powell K, Melcher K, Xu HE Sci Rep. 2017 Jan 27;7:41487. doi: 10.1038/srep41487. PMID:28128331<ref>PMID:28128331</ref>

	~~Description: Peroxisome proliferator-activated receptor gamma lignad binding domain in complex with~~ a ~~novel selectively PPAR gamma~~-~~modulating ligand VSP~~-51		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[Category: Unreleased Structures]]~~		</div>
	~~[[Category: Zhou, X.E]]~~		<div class="pdbe-citations 5two" style="background-color:#fffaf0;"></div>
	~~[[Category: Xu, H.E]]~~		== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Melcher, K]]		[[Category: Melcher, K]]
			[[Category: Shi, J]]
			[[Category: Suino-Powell, K]]
			[[Category: Xu, H E]]
	[[Category: Yi, W]]		[[Category: Yi, W]]
	~~[[Category: Shi, J]]~~
	[[Category: Zhao, G]]		[[Category: Zhao, G]]
	[[Category: ~~Suino~~-~~Powell, K~~]]		[[Category: Zhou, X E]]
			[[Category: Dna binding protein]]
			[[Category: Lignad binding domain]]
			[[Category: Peroxisome proliferator-activated receptor gamma]]
			[[Category: Selective ppar gamma ligand]]
			[[Category: Transcription]]
			[[Category: Vsp-51]]

OCA at 17:24, 15 December 2016

2016-12-15T17:24:26Z

← Older revision		Revision as of 17:24, 15 December 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 5two is ON HOLD		The entry 5two is ON HOLD until Paper Publication

	Authors: Yi, W., Shi, J., Zhao, G., Zhou, X.E., Suino-Powell, K., Melcher, K., Xu, H.E.		Authors: Yi, W., Shi, J., Zhao, G., Zhou, X.E., Suino-Powell, K., Melcher, K., Xu, H.E.

OCA: Protected "5two" [edit=sysop:move=sysop]

2016-12-09T17:58:57Z

Protected "5two" [edit=sysop:move=sysop]

← Older revision	Revision as of 17:58, 9 December 2016
(No difference)

OCA: New page: '''Unreleased structure''' The entry 5two is ON HOLD Authors: Yi, W., Shi, J., Zhao, G., Zhou, X.E., Suino-Powell, K., Melcher, K., Xu, H.E. Description: Peroxisome proliferator-activa...

2016-12-09T17:58:56Z

New page: '''Unreleased structure''' The entry 5two is ON HOLD Authors: Yi, W., Shi, J., Zhao, G., Zhou, X.E., Suino-Powell, K., Melcher, K., Xu, H.E. Description: Peroxisome proliferator-activa...

New page

'''Unreleased structure'''

The entry 5two is ON HOLD

Authors: Yi, W., Shi, J., Zhao, G., Zhou, X.E., Suino-Powell, K., Melcher, K., Xu, H.E.

Description: Peroxisome proliferator-activated receptor gamma lignad binding domain in complex with a novel selectively PPAR gamma-modulating ligand VSP-51
[[Category: Unreleased Structures]]
[[Category: Zhou, X.E]]
[[Category: Xu, H.E]]
[[Category: Melcher, K]]
[[Category: Yi, W]]
[[Category: Shi, J]]
[[Category: Zhao, G]]
[[Category: Suino-Powell, K]]