8bf1
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8bf1]] 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=8BF1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BF1 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8bf1]] 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=8BF1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BF1 FirstGlance]. <br> | ||
| - | </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=8bf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bf1 OCA], [https://pdbe.org/8bf1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bf1 RCSB], [https://www.ebi.ac.uk/pdbsum/8bf1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bf1 ProSAT]</span></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]] 1.36Å</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=8bf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bf1 OCA], [https://pdbe.org/8bf1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bf1 RCSB], [https://www.ebi.ac.uk/pdbsum/8bf1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bf1 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== 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 == | ||
| - | Di-2-ethylhexyl phthalate (DEHP) and its substitute 1,2-cyclohexane dicarboxylic acid diisononyl ester (DINCH) are widely used as plasticizers but may have adverse health effects. Via hydrolysis of one of the two ester bonds in the human body, DEHP and DINCH form the monoesters MEHP and MINCH, respectively. Previous studies demonstrated binding of these metabolites to PPARgamma and the induction of adipogenesis via this pathway. Detailed structural understanding of how these metabolites interact with PPARgamma and thereby affect human health is lacking until now. We therefore characterized the binding modes of MINCH and MEHP to the ligand binding domain of PPARgamma by X-ray crystallography and molecular dynamics (MD) simulations. Both compounds bind to the activating function-2 (AF-2) binding site via an interaction of the free carboxylates with the histidines 323 and 449, tyrosine 473 and serine 289. The alkyl chains form hydrophobic interactions with the tunnel next to cysteine 285. These binding modes are generally stable as demonstrated by the MD simulations and they resemble the complexation of fatty acids and their metabolites to the AF-2 site of PPARgamma. Similar to the situation for these natural PPARgamma agonists, the interaction of the free carboxylate groups of MEHP and MINCH with tyrosine 473 and surrounding residues stabilizes the AF-2 helix in the upward conformation. This state promotes binding of coactivator proteins and thus formation of the active complex for transcription of the specific target genes. Moreover, a comparison of the residues involved in binding of the plasticizer metabolites in vertebrate PPARgamma orthologs shows that these compounds likely have similar effects in other species. | ||
| - | + | ==See Also== | |
| - | + | *[[Peroxisome proliferator-activated receptor 3D structures|Peroxisome proliferator-activated receptor 3D structures]] | |
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== References == | == References == | ||
<references/> | <references/> | ||
Current revision
High-resolution structure of unliganded PPAR gamma in complex with the peptide PGC-1 alpha
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