5azt | pdb_00005azt
Ternary complex of hPPARalpha ligand binding domain, 17-oxoDHA and a SRC1 peptide
Structural highlights
FunctionPPARA_HUMAN Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety (By similarity). Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2.[1] [2] [3] [4] Publication Abstract from PubMed17-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[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
