5AZT

Ternary complex of hPPARalpha ligand binding domain, 17-oxoDHA and a SRC1 peptide

Summary for 5AZT

• Entry DOI: 10.2210/pdb5azt/pdb
• Related: 5AZV
• Descriptor: Peroxisome proliferator-activated receptor alpha, 15-meric peptide from Nuclear receptor coactivator 1, (4~{Z},7~{Z},10~{Z},13~{Z},19~{Z})-17-oxidanylidenedocosa-4,7,10,13,19-pentaenoic acid, ... (4 entities in total)
• Functional Keywords: nuclear receptor, transcription regulation, ligand binding domain, zinc-finger, dna binding, transcription, obesity, nucleus, receptor, activator, oxidized fatty acid, transcription factor, agonist, dual agonist, covalent, ppre, nuclear, co-activator, dna binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 63266.19

Authors

Egawa, D.,Itoh, T.,Yamamoto, K. (deposition date: 2015-10-23, release date: 2016-07-06, Last modification date: 2024-10-30)

Primary citation

Egawa, D.,Itoh, T.,Akiyama, Y.,Saito, T.,Yamamoto, K.
17-OxoDHA Is a PPAR alpha/gamma Dual Covalent Modifier and Agonist
Acs Chem.Biol., 2016

PubMed Abstract: 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 γ (PPARγ) and PPARα in transcriptional assays and thus can be classified as an α/γ dual agonist. ESI mass spectroscopy and X-ray crystallographic analysis showed that 17-oxoDHA binds to PPARγ and PPARα covalently, making 17-oxoDHA the first of a novel class of PPAR agonists, the PPARα/γ dual covalent agonist. Furthermore, the covalent binding sites were identified as Cys285 for PPARγ and Cys275 for PPARα.

PubMed: 27337155
DOI: 10.1021/acschembio.6b00338

Experimental method

X-RAY DIFFRACTION (3.45 Å)