3X1I

hPPARgamma Ligand binding domain in complex with 6-oxo-tetracosahexaenoic acid

Summary for 3X1I

• Entry DOI: 10.2210/pdb3x1i/pdb
• Related: 3X1H
• Descriptor: Peroxisome proliferator-activated receptor gamma, (8E,12Z,15Z,18Z,21Z)-6-oxotetracosa-8,12,15,18,21-pentaenoic acid (3 entities in total)
• Functional Keywords: nuclear receptor, transcription regulation, ligand binding domain, diabetes mellitus, zinc-finger, dna-binding, transcription, obesity
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 63644.12

Authors

Egawa, D.,Itoh, T.,Yamamoto, K. (deposition date: 2014-11-18, release date: 2015-04-08, Last modification date: 2024-10-16)

Primary citation

Egawa, D.,Itoh, T.,Yamamoto, K.
Characterization of covalent bond formation between PPAR gamma and oxo-fatty acids.
Bioconjug.Chem., 26:690-698, 2015

PubMed Abstract: Covalent modification of proteins is important for normal cellular regulation. Here, we report on the covalent modification of peroxisome proliferator-activated receptor γ (PPARγ), an important drug target, by oxo-fatty acids. In this study, ESI mass spectroscopy showed that the reactivities of oxo-fatty acids with PPARγ are different from one another and that these behaviors are related to the structure of the fatty acids. X-ray crystallography showed that three oxo-fatty acids all bound to the same residue of PPARγ (Cys285), but displayed different hydrogen bonding modes. Moreover, fatty acids formed covalent bonds with both PPARγ moieties in the homodimer, one in an active conformation and the other in an alternative conformation. These two conformations may explain why covalently bound fatty acids show partial rather than full agonist activity.

PubMed: 25785518
DOI: 10.1021/acs.bioconjchem.5b00021

Experimental method

X-RAY DIFFRACTION (2.4 Å)