4e4k - Revision history

OCA at 11:01, 1 March 2024

2024-03-01T11:01:42Z

← Older revision		Revision as of 11:01, 1 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4k]] 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=4E4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4K FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4k]] 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=4E4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4K FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RRG:(2S)-3-PHENYL-2-{[2-(PROPAN-2-YL)BIPHENYL-4-YL]OXY}PROPANOIC+ACID'>RRG</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]] 2.5Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RRG:(2S)-3-PHENYL-2-{[2-(PROPAN-2-YL)BIPHENYL-4-YL]OXY}PROPANOIC+ACID'>RRG</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=4e4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4k OCA], [https://pdbe.org/4e4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4k RCSB], [https://www.ebi.ac.uk/pdbsum/4e4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4k 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=4e4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4k OCA], [https://pdbe.org/4e4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4k RCSB], [https://www.ebi.ac.uk/pdbsum/4e4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4k ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[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.		[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 ==
	[[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>		[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 ==~~
	The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma) dual agonist 1, allowed the identification of new ligands with higher potency on PPARalpha and fine-tuned moderate PPARgamma activity. For the most promising stereoisomer (S)-16, X-ray and calorimetric studies in PPARgamma revealed, at high ligand concentration, the presence of two molecules simultaneously bound to the receptor. On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPARalpha and PPARgamma, respectively. The effects of (S)-16 on mitochondrial acylcarnitine carrier and carnitine-palmitoyl-transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPARalpha agonist fibrates currently used in therapy.

	New 2-(Aryloxy)-3-phenylpropanoic Acids as Peroxisome Proliferator-Activated Receptor alpha/gamma Dual Agonists Able To Upregulate Mitochondrial Carnitine Shuttle System Gene Expression.,Laghezza A, Pochetti G, Lavecchia A, Fracchiolla G, Faliti S, Piemontese L, Di Giovanni C, Iacobazzi V, Infantino V, Montanari R, Capelli D, Tortorella P, Loiodice F J Med Chem. 2013 Jan 10;56(1):60-72. doi: 10.1021/jm301018z. Epub 2012 Dec 18. PMID:23171045<ref>PMID:23171045</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e4k" style="background-color:#fffaf0;"></div~~>

	==See Also==		==See Also==

OCA at 06:49, 28 September 2022

2022-09-28T06:49:38Z

← Older revision		Revision as of 06:49, 28 September 2022
Line 1:		Line 1:

	==Crystal Structure of PPARgamma with the ligand JO21==		==Crystal Structure of PPARgamma with the ligand JO21==
	<StructureSection load='4e4k' size='340' side='right' caption='[[4e4k]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4e4k' size='340' side='right'caption='[[4e4k]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4k]] 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=4E4K OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E4K FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4k]] 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=4E4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4K FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RRG:(2S)-3-PHENYL-2-{[2-(PROPAN-2-YL)BIPHENYL-4-YL]OXY}PROPANOIC+ACID'>RRG</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=RRG:(2S)-3-PHENYL-2-{[2-(PROPAN-2-YL)BIPHENYL-4-YL]OXY}PROPANOIC+ACID'>RRG</scene></td></tr>
	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3b3k\|3b3k]], [[3k8s\|3k8s]], [[4e4q\|4e4q]]</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=4e4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4k OCA], [https://pdbe.org/4e4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4k RCSB], [https://www.ebi.ac.uk/pdbsum/4e4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4k ProSAT]</span></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=4e4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4k OCA], [~~http~~://pdbe.org/4e4k PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e4k RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e4k PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4k 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 24:		Line 22:

	==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: Carbonara, G]]		[[Category: Large Structures]]
	[[Category: Fracchiolla, G]]		[[Category: Carbonara G]]
	[[Category: Laghezza, A]]		[[Category: Fracchiolla G]]
	[[Category: Lavecchia, A]]		[[Category: Laghezza A]]
	[[Category: Loiodice, F]]		[[Category: Lavecchia A]]
	[[Category: Montanari, R]]		[[Category: Loiodice F]]
	[[Category: Novellino, E]]		[[Category: Montanari R]]
	[[Category: Piemontese, L]]		[[Category: Novellino E]]
	[[Category: Pochetti, G]]		[[Category: Piemontese L]]
	~~[[Category: Bundle of alpha-helices and a small four-stranded beta-sheet]]~~		[[Category: Pochetti G]]
	~~[[Category: Transcription]]~~
	~~[[Category: Transcription factor~~]]

OCA at 02:42, 11 December 2016

2016-12-11T02:42:03Z

← Older revision		Revision as of 02:42, 11 December 2016
Line 1:		Line 1:

	==Crystal Structure of PPARgamma with the ligand JO21==		==Crystal Structure of PPARgamma with the ligand JO21==
	<StructureSection load='4e4k' size='340' side='right' caption='[[4e4k]], [[Resolution\|resolution]] 2.50Å' scene=''>		<StructureSection load='4e4k' size='340' side='right' caption='[[4e4k]], [[Resolution\|resolution]] 2.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4K FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4k]] 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=4E4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4K FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RRG:(2S)-3-PHENYL-2-{[2-(PROPAN-2-YL)BIPHENYL-4-YL]OXY}PROPANOIC+ACID'>RRG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RRG:(2S)-3-PHENYL-2-{[2-(PROPAN-2-YL)BIPHENYL-4-YL]OXY}PROPANOIC+ACID'>RRG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3b3k\|3b3k]], [[3k8s\|3k8s]], [[4e4q\|4e4q]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3b3k\|3b3k]], [[3k8s\|3k8s]], [[4e4q\|4e4q]]</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 ~~Homo sapiens~~])</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=4e4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4k RCSB], [http://www.ebi.ac.uk/pdbsum/4e4k PDBsum]</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=4e4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4k OCA], [http://pdbe.org/4e4k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e4k RCSB], [http://www.ebi.ac.uk/pdbsum/4e4k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4k ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 4e4k" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 27:		Line 29:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Carbonara, G]]		[[Category: Carbonara, G]]
	[[Category: Fracchiolla, G]]		[[Category: Fracchiolla, G]]

OCA at 16:35, 9 December 2014

2014-12-09T16:35:28Z

← Older revision		Revision as of 16:35, 9 December 2014
Line 1:		Line 1:
	[[~~Image~~:~~4e4k~~.~~jpg~~\|~~left~~\|~~200px~~]]		==Crystal Structure of PPARgamma with the ligand JO21==
			<StructureSection load='4e4k' size='340' side='right' caption='[[4e4k]], [[Resolution\|resolution]] 2.50Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[4e4k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4K FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=RRG:(2S)-3-PHENYL-2-{[2-(PROPAN-2-YL)BIPHENYL-4-YL]OXY}PROPANOIC+ACID'>RRG</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3b3k\|3b3k]], [[3k8s\|3k8s]], [[4e4q\|4e4q]]</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 Homo sapiens])</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=4e4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4k RCSB], [http://www.ebi.ac.uk/pdbsum/4e4k PDBsum]</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 ==
			The preparation of a series of 2-(aryloxy)-3-phenylpropanoic acids, resulting from the introduction of different substituents into the biphenyl system of the previously reported peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma) dual agonist 1, allowed the identification of new ligands with higher potency on PPARalpha and fine-tuned moderate PPARgamma activity. For the most promising stereoisomer (S)-16, X-ray and calorimetric studies in PPARgamma revealed, at high ligand concentration, the presence of two molecules simultaneously bound to the receptor. On the basis of these results and docking experiments in both receptor subtypes, a molecular explanation was provided for its different behavior as a full and partial agonist of PPARalpha and PPARgamma, respectively. The effects of (S)-16 on mitochondrial acylcarnitine carrier and carnitine-palmitoyl-transferase 1 gene expression, two key components of the carnitine shuttle system, were also investigated, allowing the hypothesis of a more beneficial pharmacological profile of this compound compared to the less potent PPARalpha agonist fibrates currently used in therapy.

	~~{{STRUCTURE_4e4k\| PDB=4e4k \| SCENE= }}~~		New 2-(Aryloxy)-3-phenylpropanoic Acids as Peroxisome Proliferator-Activated Receptor alpha/gamma Dual Agonists Able To Upregulate Mitochondrial Carnitine Shuttle System Gene Expression.,Laghezza A, Pochetti G, Lavecchia A, Fracchiolla G, Faliti S, Piemontese L, Di Giovanni C, Iacobazzi V, Infantino V, Montanari R, Capelli D, Tortorella P, Loiodice F J Med Chem. 2013 Jan 10;56(1):60-72. doi: 10.1021/jm301018z. Epub 2012 Dec 18. PMID:23171045<ref>PMID:23171045</ref>

	~~===Crystal Structure~~ of ~~PPARgamma with~~ the ~~ligand JO21===~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	~~{{ABSTRACT_PUBMED_23171045}}~~		==See Also==
			*[[Peroxisome Proliferator-Activated Receptors\|Peroxisome Proliferator-Activated Receptors]]
	==~~About this Structure~~==		== References ==
	[[~~4e4k~~]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4K OCA].		<references/>
			__TOC__
	==~~Reference~~==		</StructureSection>
	<~~ref group="xtra">PMID:019053776<~~/~~ref><ref group="xtra">PMID:018263587</ref~~><~~references group="xtra"~~/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Carbonara, G.]]		[[Category: Carbonara, G]]
	[[Category: Fracchiolla, G.]]		[[Category: Fracchiolla, G]]
	[[Category: Laghezza, A.]]		[[Category: Laghezza, A]]
	[[Category: Lavecchia, A.]]		[[Category: Lavecchia, A]]
	[[Category: Loiodice, F.]]		[[Category: Loiodice, F]]
	[[Category: Montanari, R.]]		[[Category: Montanari, R]]
	[[Category: Novellino, E.]]		[[Category: Novellino, E]]
	[[Category: Piemontese, L.]]		[[Category: Piemontese, L]]
	[[Category: Pochetti, G.]]		[[Category: Pochetti, G]]
	[[Category: Bundle of alpha-helices and a small four-stranded beta-sheet]]		[[Category: Bundle of alpha-helices and a small four-stranded beta-sheet]]
	[[Category: Transcription]]		[[Category: Transcription]]
	[[Category: Transcription factor]]		[[Category: Transcription factor]]

OCA at 11:37, 23 January 2013

2013-01-23T11:37:46Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:4e4k.jpg|left|200px]]
-The entry 4e4k is ON HOLD  until Paper Publication
+{{STRUCTURE_4e4k|  PDB=4e4k  |  SCENE=  }}
-Authors: Pochetti, G., Montanari, R., Loiodice, F., Fracchiolla, G., Laghezza, A., Carbonara, G., Piemontese, L., Lavecchia, A., Novellino, E.
+===Crystal Structure of PPARgamma with the ligand JO21===
-Description: Crystal Structure of PPARgamma with the ligand JO21
+{{ABSTRACT_PUBMED_23171045}}

OCA at 06:25, 17 October 2012

2012-10-17T06:25:57Z

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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4e4k is ON HOLD		The entry 4e4k is ON HOLD until Paper Publication

	Authors: Pochetti, G., Montanari, R., Loiodice, F., Fracchiolla, G., Laghezza, A., Carbonara, G., Piemontese, L., Lavecchia, A., Novellino, E.		Authors: Pochetti, G., Montanari, R., Loiodice, F., Fracchiolla, G., Laghezza, A., Carbonara, G., Piemontese, L., Lavecchia, A., Novellino, E.

	Description: Crystal Structure of PPARgamma with the ligand JO21		Description: Crystal Structure of PPARgamma with the ligand JO21

OCA: Protected "4e4k" [edit=sysop:move=sysop]

2012-03-21T07:16:58Z

Protected "4e4k" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:16, 21 March 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4e4k is ON HOLD Authors: Pochetti, G., Montanari, R., Loiodice, F., Fracchiolla, G., Laghezza, A., Carbonara, G., Piemontese, L., Lavecchia, A., Nov...

2012-03-21T07:16:57Z

New page: '''Unreleased structure''' The entry 4e4k is ON HOLD Authors: Pochetti, G., Montanari, R., Loiodice, F., Fracchiolla, G., Laghezza, A., Carbonara, G., Piemontese, L., Lavecchia, A., Nov...

New page

'''Unreleased structure'''

The entry 4e4k is ON HOLD

Authors: Pochetti, G., Montanari, R., Loiodice, F., Fracchiolla, G., Laghezza, A., Carbonara, G., Piemontese, L., Lavecchia, A., Novellino, E.

Description: Crystal Structure of PPARgamma with the ligand JO21