5azv
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of hPPARgamma ligand binding domain complexed with 17-oxoDHA== | |
| + | <StructureSection load='5azv' size='340' side='right' caption='[[5azv]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5azv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AZV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AZV FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4M5:(4~{Z},7~{Z},10~{Z},13~{Z},19~{Z})-17-OXIDANYLIDENEDOCOSA-4,7,10,13,19-PENTAENOIC+ACID'>4M5</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5azt|5azt]]</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=5azv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5azv OCA], [http://pdbe.org/5azv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5azv RCSB], [http://www.ebi.ac.uk/pdbsum/5azv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5azv 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 17-Hydroxy docosahexaenoic acid (17-HDHA) is an oxidized form of docosahexaenoic acid (DHA) and known as a specialized proresolving mediator. We found that a further oxidized product, 17-oxodocosahexaenoic acid (17-oxoDHA), activates peroxisome proliferator-activated receptors gamma (PPARgamma) and PPARalpha in transcriptional assays and thus can be classified as an alpha/gamma dual agonist. ESI mass spectroscopy and X-ray crystallographic analysis showed that 17-oxoDHA binds to PPARgamma and PPARalpha covalently, making 17-oxoDHA the first of a novel class of PPAR agonists, the PPARalpha/gamma dual covalent agonist. Furthermore, the covalent binding sites were identified as Cys285 for PPARgamma and Cys275 for PPARalpha. | ||
| - | + | 17-OxoDHA Is a PPARalpha/gamma Dual Covalent Modifier and Agonist.,Egawa D, Itoh T, Akiyama Y, Saito T, Yamamoto K ACS Chem Biol. 2016 Jul 1. PMID:27337155<ref>PMID:27337155</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5azv" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Egawa, D]] | [[Category: Egawa, D]] | ||
[[Category: Itoh, T]] | [[Category: Itoh, T]] | ||
| + | [[Category: Yamamoto, K]] | ||
| + | [[Category: Activator]] | ||
| + | [[Category: Agonist]] | ||
| + | [[Category: Covalent]] | ||
| + | [[Category: Dna binding]] | ||
| + | [[Category: Dna binding protein]] | ||
| + | [[Category: Dual agonist]] | ||
| + | [[Category: Ligand binding domain]] | ||
| + | [[Category: Nuclear]] | ||
| + | [[Category: Nuclear receptor]] | ||
| + | [[Category: Nucleus]] | ||
| + | [[Category: Obesity]] | ||
| + | [[Category: Oxidized fatty acid]] | ||
| + | [[Category: Ppre]] | ||
| + | [[Category: Receptor]] | ||
| + | [[Category: Transcription]] | ||
| + | [[Category: Transcription factor]] | ||
| + | [[Category: Transcription regulation]] | ||
| + | [[Category: Zinc-finger]] | ||
Revision as of 02:14, 13 July 2016
Crystal structure of hPPARgamma ligand binding domain complexed with 17-oxoDHA
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Categories: Egawa, D | Itoh, T | Yamamoto, K | Activator | Agonist | Covalent | Dna binding | Dna binding protein | Dual agonist | Ligand binding domain | Nuclear | Nuclear receptor | Nucleus | Obesity | Oxidized fatty acid | Ppre | Receptor | Transcription | Transcription factor | Transcription regulation | Zinc-finger
