5gtp - Revision history

OCA at 11:42, 2 August 2023

2023-08-02T11:42:14Z

←Older revision		Revision as of 11:42, 2 August 2023
Line 3:		Line 3:
	<StructureSection load='5gtp' size='340' side='right'caption='[[5gtp]], [[Resolution\|resolution]] 2.35Å' scene=''>		<StructureSection load='5gtp' size='340' side='right'caption='[[5gtp]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5gtp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GTP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5GTP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5gtp]] 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=5GTP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GTP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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]] 2.35Å</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=5gtp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtp OCA], [~~http~~://pdbe.org/5gtp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5gtp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5gtp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtp ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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=5gtp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtp OCA], [https://pdbe.org/5gtp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gtp RCSB], [https://www.ebi.ac.uk/pdbsum/5gtp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtp 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 22:		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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Jang~~, J Y~~]]	+	[[Category: Jang JY]]
-	[[Category: Suh~~, S W]]~~	+	[[Category: Suh SW]]
-	~~[[Category: Ppargamma]]~~	+
-	~~[[Category: Src-1]]~~	+
-	~~[[Category: Transcription~~]]	+

OCA at 06:43, 20 May 2020

2020-05-20T06:43:15Z

←Older revision		Revision as of 06:43, 20 May 2020
Line 1:		Line 1:

	==The agonist-free structure of human PPARgamma ligand binding domain in the presence of the SRC-1 coactivator peptide==		==The agonist-free structure of human PPARgamma ligand binding domain in the presence of the SRC-1 coactivator peptide==
-	<StructureSection load='5gtp' size='340' side='right' caption='[[5gtp]], [[Resolution\|resolution]] 2.35Å' scene=''>	+	<StructureSection load='5gtp' size='340' side='right'caption='[[5gtp]], [[Resolution\|resolution]] 2.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5gtp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GTP OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5GTP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5gtp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GTP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GTP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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=5gtp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtp OCA], [http://pdbe.org/5gtp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gtp RCSB], [http://www.ebi.ac.uk/pdbsum/5gtp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtp ProSAT]</span></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=5gtp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtp OCA], [http://pdbe.org/5gtp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gtp RCSB], [http://www.ebi.ac.uk/pdbsum/5gtp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtp ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5gtp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5gtp" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Phenylethanolamine N-methyltransferase 3D structures\|Phenylethanolamine N-methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Jang, J Y]]		[[Category: Jang, J Y]]
	[[Category: Suh, S W]]		[[Category: Suh, S W]]

OCA at 03:53, 30 August 2017

2017-08-30T03:53:56Z

←Older revision		Revision as of 03:53, 30 August 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The ~~entry~~ 5gtp is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==The agonist-free structure of human PPARgamma ligand binding domain in the presence of the SRC-1 coactivator peptide==
		+	<StructureSection load='5gtp' size='340' side='right' caption='[[5gtp]], [[Resolution\|resolution]] 2.35Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5gtp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GTP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GTP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYR:MYRISTIC+ACID'>MYR</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=5gtp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtp OCA], [http://pdbe.org/5gtp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gtp RCSB], [http://www.ebi.ac.uk/pdbsum/5gtp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtp 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 ==
		+	Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPARgamma agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPARgamma LBD; it is located beside the Omega loop between the helices H2' and H3. We reported previously that the chirality of two optimized enantiomeric PPARgamma ligands (S35 and R35) differentiates their PPARgamma transcriptional activity, binding affinity, and inhibitory activity toward Cdk5 (cyclin-dependent kinase 5)-mediated phosphorylation of PPARgamma at Ser245 (in PPARgamma1 numbering; Ser273 in PPARgamma2 numbering). S35 is a PPARgamma phosphorylation inhibitor with promising glucose uptake potential, whereas R35 behaves as a potent conventional PPARgamma agonist. To provide a structural basis for understanding the differential activities of these enantiomeric ligands, we have determined crystal structures of the PPARgamma LBD in complex with either S35 or R35. S35 and R35 bind to the PPARgamma LBD in significantly different manners. The partial agonist S35 occupies the alternate site near the Omega loop, whereas the full agonist R35 binds entirely to the canonical LBP. Alternate site binding of S35 affects the PPARgamma transactivation and the inhibitory effect on PPARgamma Ser245 phosphorylation. This study provides a useful platform for the development of a new generation of PPARgamma ligands as anti-diabetic drug candidates.

-	~~Authors~~: Jang, J.Y., ~~Suh, S~~.W.	+	Structural basis for differential activities of enantiomeric PPARgamma agonists: Binding of S35 to the alternate site.,Jang JY, Koh M, Bae H, An DR, Im HN, Kim HS, Yoon JY, Yoon HJ, Han BW, Park SB, Suh SW Biochim Biophys Acta. 2017 Jun;1865(6):674-681. doi:, 10.1016/j.bbapap.2017.03.008. Epub 2017 Mar 22. PMID:28342850<ref>PMID:28342850</ref>

-	~~Description: The agonist-free structure~~ of ~~human PPARgamma ligand binding domain in~~ the ~~presence~~ of ~~the SRC~~-~~1 coactivator peptide~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Suh, S.W]]	+	<div class="pdbe-citations 5gtp" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Jang, J.Y~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Jang, J Y]]
		+	[[Category: Suh, S W]]
		+	[[Category: Ppargamma]]
		+	[[Category: Src-1]]
		+	[[Category: Transcription]]

OCA at 08:37, 21 September 2016

2016-09-21T08:37:17Z

←Older revision		Revision as of 08:37, 21 September 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5gtp is ON HOLD	+	The entry 5gtp is ON HOLD until Paper Publication

	Authors: Jang, J.Y., Suh, S.W.		Authors: Jang, J.Y., Suh, S.W.

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

2016-09-09T12:03:58Z

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

←Older revision

Revision as of 12:03, 9 September 2016

OCA: New page: '''Unreleased structure''' The entry 5gtp is ON HOLD Authors: Jang, J.Y., Suh, S.W. Description: The agonist-free structure of human PPARgamma ligand binding domain in the presence of ...

2016-09-09T12:03:57Z

New page: '''Unreleased structure''' The entry 5gtp is ON HOLD Authors: Jang, J.Y., Suh, S.W. Description: The agonist-free structure of human PPARgamma ligand binding domain in the presence of ...

New page

'''Unreleased structure'''

The entry 5gtp is ON HOLD

Authors: Jang, J.Y., Suh, S.W.

Description: The agonist-free structure of human PPARgamma ligand binding domain in the presence of the SRC-1 coactivator peptide
[[Category: Unreleased Structures]]
[[Category: Suh, S.W]]
[[Category: Jang, J.Y]]