6an1 - Revision history

OCA at 14:17, 13 March 2024

OCA — Wed, 13 Mar 2024 14:17:44 GMT

←Older revision		Revision as of 14:17, 13 March 2024
Line 3:		Line 3:
	<StructureSection load='6an1' size='340' side='right'caption='[[6an1]], [[Resolution\|resolution]] 2.69Å' scene=''>		<StructureSection load='6an1' size='340' side='right'caption='[[6an1]], [[Resolution\|resolution]] 2.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6an1]] 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=6AN1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6AN1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6an1]] 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=6AN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AN1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BKY:4-({2-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]phenoxy}methyl)benzoic+acid'>BKY</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]] 2.687Å</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=BKY:4-({2-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]phenoxy}methyl)benzoic+acid'>BKY</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=6an1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6an1 OCA], [~~http~~://pdbe.org/6an1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6an1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6an1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6an1 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=6an1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6an1 OCA], [https://pdbe.org/6an1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6an1 RCSB], [https://www.ebi.ac.uk/pdbsum/6an1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6an1 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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor, playing key roles in maintenance of adipose tissue and in regulation of glucose and lipid homeostasis. This receptor is the target of thiazolidinediones, a class of antidiabetic drugs, which improve insulin sensitization and regulate glycemia in type 2 diabetes. Despite the beneficial effects of drugs, such as rosiglitazone and pioglitazone, their use is associated with several side effects, including weight gain, heart failure, and liver disease, since these drugs induce full activation of the receptor. By contrast, a promising activation-independent mechanism that involves the inhibition of cyclin-dependent kinase 5 (CDK5)-mediated PPARgamma phosphorylation has been related to the insulin-sensitizing effects induced by these drugs. Thus, we aimed to identify novel PPARgamma ligands that do not possess agonist properties by conducting a mini-trial with 80 compounds using the sequential steps of thermal shift assay, 8-anilino-1-naphthalenesulfonic acid fluorescence quenching, and a cell-based transactivation assay. We identified two non-agonist PPARgamma ligands, AM-879 and P11, and one partial-agonist, R32. Using fluorescence anisotropy, we show that AM-879 does not dissociate the NCOR corepressor in vitro, and it has only a small effect on TRAP coactivator recruitment. In cells, AM-879 could not induce adipocyte differentiation or positively regulate the expression of genes associated with adipogenesis. In addition, AM-879 inhibited CDK5-mediated phosphorylation of PPARgamma in vitro. Taken together, these findings supported an interaction between AM-879 and PPARgamma; this interaction was identified by the analysis of the crystal structure of the PPARgamma:AM-879 complex and evidenced by AM-879's mechanism of action as a putative PPARgamma non-agonist with antidiabetic properties. Moreover, we present an optimized assay pipeline capable of detecting ligands that physically bind to PPARgamma but do not cause its activation as a new strategy to identify ligands for this nuclear receptor.	+
-		+
-	Screening for PPAR Non-Agonist Ligands Followed by Characterization of a Hit, AM-879, with Additional No-Adipogenic and cdk5-Mediated Phosphorylation Inhibition Properties.,Ribeiro Filho HV, Bernardi Videira N, Bridi AV, Tittanegro TH, Helena Batista FA, de Carvalho Pereira JG, de Oliveira PSL, Bajgelman MC, Le Maire A, Figueira ACM Front Endocrinol (Lausanne). 2018 Feb 1;9:11. doi: 10.3389/fendo.2018.00011., eCollection 2018. PMID:29449830<ref>PMID:29449830</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6an1" style="background-color:#fffaf0;"></div~~>	+

	==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: Figueira~~, A C]]~~	+	[[Category: Figueira AC]]
-	~~[[Category: Maire, A le~~]]	+	[[Category: Veras H]]
-	[[Category: Veras, H]]	+	[[Category: Le Maire A]]
-	[[Category: ~~Ligand binding domain]]~~	+
-	~~[[Category: Nuclear protein]]~~	+
-	~~[[Category: Nuclear receptor~~]]	+

OCA at 10:04, 1 January 2020

OCA — Wed, 01 Jan 2020 10:04:05 GMT

←Older revision		Revision as of 10:04, 1 January 2020
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[~~Peroxisome Proliferator~~-~~Activated Receptors~~\|~~Peroxisome Proliferator~~-~~Activated Receptors~~]]	+	*[[Phenylethanolamine N-methyltransferase 3D structures\|Phenylethanolamine N-methyltransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 06:35, 17 April 2019

OCA — Wed, 17 Apr 2019 06:35:14 GMT

←Older revision		Revision as of 06:35, 17 April 2019
Line 1:		Line 1:

	==Crystal structure of the complex between PPARgamma LBD and the ligand AM-879==		==Crystal structure of the complex between PPARgamma LBD and the ligand AM-879==
-	<StructureSection load='6an1' size='340' side='right' caption='[[6an1]], [[Resolution\|resolution]] 2.69Å' scene=''>	+	<StructureSection load='6an1' size='340' side='right'caption='[[6an1]], [[Resolution\|resolution]] 2.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6an1]] 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=6AN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AN1 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6an1]] 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=6AN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AN1 FirstGlance]. <br>
Line 21:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6an1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6an1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Peroxisome Proliferator-Activated Receptors\|Peroxisome Proliferator-Activated Receptors]]
	== References ==		== References ==
	<references/>		<references/>
Line 26:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Figueira, A C]]		[[Category: Figueira, A C]]
	[[Category: Maire, A le]]		[[Category: Maire, A le]]

OCA at 06:42, 18 April 2018

OCA — Wed, 18 Apr 2018 06:42:26 GMT

←Older revision		Revision as of 06:42, 18 April 2018
Line 3:		Line 3:
	<StructureSection load='6an1' size='340' side='right' caption='[[6an1]], [[Resolution\|resolution]] 2.69Å' scene=''>		<StructureSection load='6an1' size='340' side='right' caption='[[6an1]], [[Resolution\|resolution]] 2.69Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6an1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AN1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6an1]] 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=6AN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AN1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BKY:4-({2-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]phenoxy}methyl)benzoic+acid'>BKY</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BKY:4-({2-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]phenoxy}methyl)benzoic+acid'>BKY</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=6an1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6an1 OCA], [http://pdbe.org/6an1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6an1 RCSB], [http://www.ebi.ac.uk/pdbsum/6an1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6an1 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=6an1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6an1 OCA], [http://pdbe.org/6an1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6an1 RCSB], [http://www.ebi.ac.uk/pdbsum/6an1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6an1 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 ==
		+	Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor, playing key roles in maintenance of adipose tissue and in regulation of glucose and lipid homeostasis. This receptor is the target of thiazolidinediones, a class of antidiabetic drugs, which improve insulin sensitization and regulate glycemia in type 2 diabetes. Despite the beneficial effects of drugs, such as rosiglitazone and pioglitazone, their use is associated with several side effects, including weight gain, heart failure, and liver disease, since these drugs induce full activation of the receptor. By contrast, a promising activation-independent mechanism that involves the inhibition of cyclin-dependent kinase 5 (CDK5)-mediated PPARgamma phosphorylation has been related to the insulin-sensitizing effects induced by these drugs. Thus, we aimed to identify novel PPARgamma ligands that do not possess agonist properties by conducting a mini-trial with 80 compounds using the sequential steps of thermal shift assay, 8-anilino-1-naphthalenesulfonic acid fluorescence quenching, and a cell-based transactivation assay. We identified two non-agonist PPARgamma ligands, AM-879 and P11, and one partial-agonist, R32. Using fluorescence anisotropy, we show that AM-879 does not dissociate the NCOR corepressor in vitro, and it has only a small effect on TRAP coactivator recruitment. In cells, AM-879 could not induce adipocyte differentiation or positively regulate the expression of genes associated with adipogenesis. In addition, AM-879 inhibited CDK5-mediated phosphorylation of PPARgamma in vitro. Taken together, these findings supported an interaction between AM-879 and PPARgamma; this interaction was identified by the analysis of the crystal structure of the PPARgamma:AM-879 complex and evidenced by AM-879's mechanism of action as a putative PPARgamma non-agonist with antidiabetic properties. Moreover, we present an optimized assay pipeline capable of detecting ligands that physically bind to PPARgamma but do not cause its activation as a new strategy to identify ligands for this nuclear receptor.
		+
		+	Screening for PPAR Non-Agonist Ligands Followed by Characterization of a Hit, AM-879, with Additional No-Adipogenic and cdk5-Mediated Phosphorylation Inhibition Properties.,Ribeiro Filho HV, Bernardi Videira N, Bridi AV, Tittanegro TH, Helena Batista FA, de Carvalho Pereira JG, de Oliveira PSL, Bajgelman MC, Le Maire A, Figueira ACM Front Endocrinol (Lausanne). 2018 Feb 1;9:11. doi: 10.3389/fendo.2018.00011., eCollection 2018. PMID:29449830<ref>PMID:29449830</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6an1" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Figueira, A C]]		[[Category: Figueira, A C]]
	[[Category: Maire, A le]]		[[Category: Maire, A le]]

OCA at 06:32, 15 February 2018

OCA — Thu, 15 Feb 2018 06:32:13 GMT

←Older revision		Revision as of 06:32, 15 February 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6an1 is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of the complex between PPARgamma LBD and the ligand AM-879==
-		+	<StructureSection load='6an1' size='340' side='right' caption='[[6an1]], [[Resolution\|resolution]] 2.69Å' scene=''>
-	~~Authors~~: ~~Veras~~, H., ~~Figueira~~, A.C., ~~le Maire~~, A.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6an1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AN1 FirstGlance]. <br>
-	~~Description~~: ~~Crystal structure~~ of the ~~complex between PPARgamma LBD~~ and the ligand AM-~~879~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BKY:4-({2-[(1,3-dioxo-1,3-dihydro-2H-inden-2-ylidene)methyl]phenoxy}methyl)benzoic+acid'>BKY</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=6an1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6an1 OCA], [http://pdbe.org/6an1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6an1 RCSB], [http://www.ebi.ac.uk/pdbsum/6an1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6an1 ProSAT]</span></td></tr>
-	[[Category: Le Maire, A]]	+	</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: Figueira, A C]]
		+	[[Category: Maire, A le]]
	[[Category: Veras, H]]		[[Category: Veras, H]]
-	[[Category: ~~Figueira, A.C~~]]	+	[[Category: Ligand binding domain]]
		+	[[Category: Nuclear protein]]
		+	[[Category: Nuclear receptor]]

OCA at 05:43, 25 October 2017

OCA — Wed, 25 Oct 2017 05:43:00 GMT

←Older revision		Revision as of 05:43, 25 October 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6an1 is ON HOLD	+	The entry 6an1 is ON HOLD until Paper Publication

	Authors: Veras, H., Figueira, A.C., le Maire, A.		Authors: Veras, H., Figueira, A.C., le Maire, A.

OCA: Protected "6an1" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 16:34:41 GMT

Protected "6an1" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:34, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 6an1 is ON HOLD Authors: Veras, H., Figueira, A.C., le Maire, A. Description: Crystal structure of the complex between PPARgamma LBD and the ligand...

OCA — Wed, 27 Sep 2017 16:34:40 GMT

New page: '''Unreleased structure''' The entry 6an1 is ON HOLD Authors: Veras, H., Figueira, A.C., le Maire, A. Description: Crystal structure of the complex between PPARgamma LBD and the ligand...

New page

'''Unreleased structure'''

The entry 6an1 is ON HOLD

Authors: Veras, H., Figueira, A.C., le Maire, A.

Description: Crystal structure of the complex between PPARgamma LBD and the ligand AM-879
[[Category: Unreleased Structures]]
[[Category: Le Maire, A]]
[[Category: Veras, H]]
[[Category: Figueira, A.C]]