6qj5 - Revision history

OCA at 12:01, 24 January 2024

OCA — Wed, 24 Jan 2024 12:01:59 GMT

←Older revision		Revision as of 12:01, 24 January 2024
Line 3:		Line 3:
	<StructureSection load='6qj5' size='340' side='right'caption='[[6qj5]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6qj5' size='340' side='right'caption='[[6qj5]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qj5]] 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=6QJ5 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6QJ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qj5]] 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=6QJ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QJ5 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=H8R:(2~{S})-3-methyl-2~~-[~~(4-octoxyphenyl)carbonylamino~~]~~butanoic+acid'>H8R</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]] 2Å</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=H8R:(2~{S})-3-methyl-2-[(4-octoxyphenyl)carbonylamino]butanoic+acid'>H8R</scene></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=6qj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qj5 OCA], [~~http~~://pdbe.org/6qj5 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6qj5 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6qj5 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6qj5 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=6qj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qj5 OCA], [https://pdbe.org/6qj5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qj5 RCSB], [https://www.ebi.ac.uk/pdbsum/6qj5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qj5 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 28:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Capelli, D]]	+	[[Category: Capelli D]]
-	[[Category: Montanari, R]]	+	[[Category: Montanari R]]
-	[[Category: Pochetti, G]]	+	[[Category: Pochetti G]]
-	~~[[Category: Bundle of alpha-helices and small four-stranded beta-sheet]]~~	+
-	~~[[Category: Diabetes type ii]]~~	+
-	~~[[Category: Dna binding protein]]~~	+
-	~~[[Category: Dna-binding]]~~	+
-	~~[[Category: Transcription factor~~]]	+

OCA at 07:06, 25 November 2020

OCA — Wed, 25 Nov 2020 07:06:29 GMT

←Older revision		Revision as of 07:06, 25 November 2020
Line 3:		Line 3:
	<StructureSection load='6qj5' size='340' side='right'caption='[[6qj5]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6qj5' size='340' side='right'caption='[[6qj5]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6qj5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6QJ5 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6qj5]] 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=6QJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6QJ5 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H8R:(2~{S})-3-methyl-2-[(4-octoxyphenyl)carbonylamino]butanoic+acid'>H8R</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H8R:(2~{S})-3-methyl-2-[(4-octoxyphenyl)carbonylamino]butanoic+acid'>H8R</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=6qj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qj5 OCA], [http://pdbe.org/6qj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qj5 RCSB], [http://www.ebi.ac.uk/pdbsum/6qj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qj5 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://proteopedia.org/fgij/fg.htm?mol=6qj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qj5 OCA], [http://pdbe.org/6qj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qj5 RCSB], [http://www.ebi.ac.uk/pdbsum/6qj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qj5 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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 ==
		+	A proprietary library of novel N-aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound 3a that possesses weak proadipogenic and peroxisome proliferator-activated receptor gamma (PPARgamma) activating properties. The systematic optimization of 3a, in order to improve its PPARgamma agonist activity, led to the synthesis of compound 7j (N-aryl-substituted valine derivative) that possesses dual PPARgamma/PPARalpha agonistic activity. Structural and kinetic analyses reveal that 7j occupies the typical ligand binding domain of the PPARgamma agonists with, however, a unique high-affinity binding mode. Furthermore, 7j is highly effective in preventing cyclin-dependent kinase 5-mediated phosphorylation of PPARgamma serine 273. Although less proadipogenic than rosiglitazone, 7j significantly increases adipocyte insulin-stimulated glucose uptake and efficiently promotes white-to-brown adipocyte conversion. In addition, 7j prevents oleic acid-induced lipid accumulation in hepatoma cells. The unique biochemical properties and biological activities of compound 7j suggest that it would be a promising candidate for the development of compounds to reduce insulin resistance, obesity, and nonalcoholic fatty liver disease.
		+
		+	A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor gamma Binding Properties and Biological Activities.,Peiretti F, Montanari R, Capelli D, Bonardo B, Colson C, Amri EZ, Grimaldi M, Balaguer P, Ito K, Roeder RG, Pochetti G, Brunel JM J Med Chem. 2020 Nov 12;63(21):13124-13139. doi: 10.1021/acs.jmedchem.0c01555., Epub 2020 Nov 3. PMID:33142057<ref>PMID:33142057</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6qj5" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Peroxisome proliferator-activated receptor 3D structures\|Peroxisome proliferator-activated receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Capelli, D]]		[[Category: Capelli, D]]

OCA at 08:05, 5 February 2020

OCA — Wed, 05 Feb 2020 08:05:34 GMT

←Older revision		Revision as of 08:05, 5 February 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6qj5 is ~~ON HOLD until Paper Publication~~	+	==X-ray structure of PPARgamma LBD with the ligand NV1380==
-		+	<StructureSection load='6qj5' size='340' side='right'caption='[[6qj5]], [[Resolution\|resolution]] 2.00Å' scene=''>
-	~~Authors~~: ~~Pochetti~~, G., ~~Montanari~~, R., ~~Capelli~~, D.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6qj5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QJ5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QJ5 FirstGlance]. <br>
-	~~Description~~: X-~~ray structure of PPARgamma LBD~~ with the ligand ~~NV1380~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=H8R:(2~{S})-3-methyl-2-[(4-octoxyphenyl)carbonylamino]butanoic+acid'>H8R</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=6qj5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qj5 OCA], [http://pdbe.org/6qj5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qj5 RCSB], [http://www.ebi.ac.uk/pdbsum/6qj5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qj5 ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN]] Note=Defects in PPARG can lead to type 2 insulin-resistant diabetes and hyptertension. PPARG mutations may be associated with colon cancer. Defects in PPARG may be associated with susceptibility to obesity (OBESITY) [MIM:[http://omim.org/entry/601665 601665]]. It is a condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat.<ref>PMID:9753710</ref> Defects in PPARG are the cause of familial partial lipodystrophy type 3 (FPLD3) [MIM:[http://omim.org/entry/604367 604367]]. Familial partial lipodystrophies (FPLD) are a heterogeneous group of genetic disorders characterized by marked loss of subcutaneous (sc) fat from the extremities. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus and dyslipidemia.<ref>PMID:12453919</ref> <ref>PMID:11788685</ref> Genetic variations in PPARG can be associated with susceptibility to glioma type 1 (GLM1) [MIM:[http://omim.org/entry/137800 137800]]. Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, and ependymomas. Note=Polymorphic PPARG alleles have been found to be significantly over-represented among a cohort of American patients with sporadic glioblastoma multiforme suggesting a possible contribution to disease susceptibility.
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/PPARG_HUMAN PPARG_HUMAN]] Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses.<ref>PMID:9065481</ref> <ref>PMID:16150867</ref> <ref>PMID:20829347</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Capelli, D]]		[[Category: Capelli, D]]
		+	[[Category: Montanari, R]]
	[[Category: Pochetti, G]]		[[Category: Pochetti, G]]
-	[[Category: ~~Montanari, R~~]]	+	[[Category: Bundle of alpha-helices and small four-stranded beta-sheet]]
		+	[[Category: Diabetes type ii]]
		+	[[Category: Dna binding protein]]
		+	[[Category: Dna-binding]]
		+	[[Category: Transcription factor]]

OCA: Protected "6qj5" [edit=sysop:move=sysop]

OCA — Wed, 30 Jan 2019 07:02:18 GMT

Protected "6qj5" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:02, 30 January 2019

OCA: New page: '''Unreleased structure''' The entry 6qj5 is ON HOLD until Paper Publication Authors: Pochetti, G., Montanari, R., Capelli, D. Description: X-ray structure of PPARgamma LBD with the li...

OCA — Wed, 30 Jan 2019 07:02:17 GMT

New page: '''Unreleased structure''' The entry 6qj5 is ON HOLD until Paper Publication Authors: Pochetti, G., Montanari, R., Capelli, D. Description: X-ray structure of PPARgamma LBD with the li...

New page

'''Unreleased structure'''

The entry 6qj5 is ON HOLD until Paper Publication

Authors: Pochetti, G., Montanari, R., Capelli, D.

Description: X-ray structure of PPARgamma LBD with the ligand NV1380
[[Category: Unreleased Structures]]
[[Category: Capelli, D]]
[[Category: Pochetti, G]]
[[Category: Montanari, R]]