6d3e - Revision history

OCA at 15:17, 4 October 2023

OCA — Wed, 04 Oct 2023 15:17:09 GMT

←Older revision		Revision as of 15:17, 4 October 2023
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	<StructureSection load='6d3e' size='340' side='right'caption='[[6d3e]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='6d3e' size='340' side='right'caption='[[6d3e]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d3e]] 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=6D3E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6D3E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d3e]] 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=6D3E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D3E FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FT7:1-[(2,4-difluorophenyl)methyl]-2,3-dimethyl-N-[(1R)-1-phenylpropyl]-1H-indole-5-carboxamide'>FT7</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]] 2.395Å</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=FT7:1-[(2,4-difluorophenyl)methyl]-2,3-dimethyl-N-[(1R)-1-phenylpropyl]-1H-indole-5-carboxamide'>FT7</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=6d3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3e OCA], [~~http~~://pdbe.org/6d3e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6d3e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6d3e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3e 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=6d3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3e OCA], [https://pdbe.org/6d3e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d3e RCSB], [https://www.ebi.ac.uk/pdbsum/6d3e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3e 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 ==
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	</div>		</div>
	<div class="pdbe-citations 6d3e" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6d3e" 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: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bruning~~, J B~~]]	+	[[Category: Bruning JB]]
-	[[Category: Frkic~~, R L]]~~	+	[[Category: Frkic RL]]
-	~~[[Category: Drug discovery]]~~	+
-	~~[[Category: Nuclear receptor]]~~	+
-	~~[[Category: Transcription]]~~	+
-	~~[[Category: Type 2 diabetes~~]]	+

OCA at 07:46, 10 April 2019

OCA — Wed, 10 Apr 2019 07:46:22 GMT

←Older revision		Revision as of 07:46, 10 April 2019
Line 1:		Line 1:

	==PPARg LBD in Complex with SR1988==		==PPARg LBD in Complex with SR1988==
-	<StructureSection load='6d3e' size='340' side='right' caption='[[6d3e]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='6d3e' size='340' side='right'caption='[[6d3e]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6d3e]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3E FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6d3e]] 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=6D3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FT7:1-[(2,4-difluorophenyl)methyl]-2,3-dimethyl-N-[(1R)-1-phenylpropyl]-1H-indole-5-carboxamide'>FT7</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FT7:1-[(2,4-difluorophenyl)methyl]-2,3-dimethyl-N-[(1R)-1-phenylpropyl]-1H-indole-5-carboxamide'>FT7</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=6d3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3e OCA], [http://pdbe.org/6d3e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3e RCSB], [http://www.ebi.ac.uk/pdbsum/6d3e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3e 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=6d3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3e OCA], [http://pdbe.org/6d3e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3e RCSB], [http://www.ebi.ac.uk/pdbsum/6d3e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3e 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 ==
		+	Targeting peroxisome proliferator-activated receptor gamma (PPARgamma) by synthetic compounds has been shown to elicit insulin sensitising properties in type 2 diabetics. Treatment with a class of these compounds, the thiazolidinediones (TZDs), has shown adverse side effects such as weight gain, fluid retention, and congestive heart failure. This is due to their full agonist properties on the receptor, where a number of genes are upregulated beyond normal physiological levels. Lessened transactivation of PPARgamma by partial agonists has proved beneficial in terms of reducing side effects, while still maintaining insulin sensitising properties. However, some partial agonists have been associated with unfavourable pharmacokinetic profiles due to their acidic moieties, often causing partitioning to the liver. Here we present SR1988, a new partial agonist with favourable non-acid chemical properties. We used a combination of X-ray crystallography and hydrogen/deuterium exchange (HDX) to elucidate the structural basis for reduced activation of PPARgamma by SR1988. This structural analysis reveals a mechanism that decreases stabilisation of the AF2 coactivator binding surface by the ligand.
		+
		+	Structural and Dynamic Elucidation of a Non-acid PPARgamma Partial Agonist: SR1988.,Frkic RL, Chua BS, Shin Y, Pascal BD, Novick SJ, Kamenecka TM, Griffin PR, Bruning JB Nucl Receptor Res. 2018;5. doi: 10.11131/2018/101350. PMID:30906767<ref>PMID:30906767</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6d3e" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bruning, J B]]		[[Category: Bruning, J B]]
	[[Category: Frkic, R L]]		[[Category: Frkic, R L]]

OCA at 15:15, 27 February 2019

OCA — Wed, 27 Feb 2019 15:15:44 GMT

←Older revision		Revision as of 15:15, 27 February 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6d3e is ~~ON HOLD until Paper Publication~~	+	==PPARg LBD in Complex with SR1988==
-		+	<StructureSection load='6d3e' size='340' side='right' caption='[[6d3e]], [[Resolution\|resolution]] 2.40Å' scene=''>
-	~~Authors~~: ~~Frkic~~, R.L., ~~Bruning~~, J.B.	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6d3e]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3E FirstGlance]. <br>
-	~~Description~~: ~~PPARg LBD~~ in ~~Complex~~ with ~~SR1988~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FT7:1-[(2,4-difluorophenyl)methyl]-2,3-dimethyl-N-[(1R)-1-phenylpropyl]-1H-indole-5-carboxamide'>FT7</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=6d3e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3e OCA], [http://pdbe.org/6d3e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3e RCSB], [http://www.ebi.ac.uk/pdbsum/6d3e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3e ProSAT]</span></td></tr>
-	[[Category: Bruning, J.B]]	+	</table>
-	[[Category: Frkic, R.L]]	+	== 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: Bruning, J B]]
		+	[[Category: Frkic, R L]]
		+	[[Category: Drug discovery]]
		+	[[Category: Nuclear receptor]]
		+	[[Category: Transcription]]
		+	[[Category: Type 2 diabetes]]

OCA at 06:41, 2 May 2018

OCA — Wed, 02 May 2018 06:41:13 GMT

←Older revision		Revision as of 06:41, 2 May 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6d3e is ON HOLD	+	The entry 6d3e is ON HOLD until Paper Publication

	Authors: Frkic, R.L., Bruning, J.B.		Authors: Frkic, R.L., Bruning, J.B.

OCA: Protected "6d3e" [edit=sysop:move=sysop]

OCA — Wed, 25 Apr 2018 04:08:30 GMT

Protected "6d3e" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:08, 25 April 2018

OCA: New page: '''Unreleased structure''' The entry 6d3e is ON HOLD Authors: Frkic, R.L., Bruning, J.B. Description: PPARg LBD in Complex with SR1988 Category: Unreleased Structures [[Category: B...

OCA — Wed, 25 Apr 2018 04:08:29 GMT

New page: '''Unreleased structure''' The entry 6d3e is ON HOLD Authors: Frkic, R.L., Bruning, J.B. Description: PPARg LBD in Complex with SR1988 Category: Unreleased Structures [[Category: B...

New page

'''Unreleased structure'''

The entry 6d3e is ON HOLD

Authors: Frkic, R.L., Bruning, J.B.

Description: PPARg LBD in Complex with SR1988
[[Category: Unreleased Structures]]
[[Category: Bruning, J.B]]
[[Category: Frkic, R.L]]