Characterization of covalent bond formation between PPARγ and oxo-fatty acids

Bioconjugate Chemistry
Daichi EgawaKeiko Yamamoto

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.

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Citations

Jun 24, 2016·ACS Chemical Biology·Daichi EgawaKeiko Yamamoto
Jul 23, 2020·PPAR Research·Åsmund Kaupang, Trond Vidar Hansen
Jul 2, 2019·Chemical & Pharmaceutical Bulletin·Keiko Yamamoto
Mar 30, 2021·Journal of Cellular and Molecular Medicine·Hao ZhaoJian Li
May 7, 2021·Journal of Nutritional Science and Vitaminology·Satoshi KanamoriToshimasa Itoh
Sep 3, 2021·Biological & Pharmaceutical Bulletin·Daichi EgawaToshimasa Itoh

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