Binding Model of Amentoflavone to Peroxisome Proliferator-Activated Receptor γ

Human peroxisome proliferator-activated receptor gamma (hPPAR gamma) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. In this study, we verified that amentoflavone is an agonist of hPPAR gamma and probed the molecular basis of its action. It was demonstrated that amentoflavone bound hPPAR gamma with high (picomolar) affinity and increased the binding between hPPAR gamma and steroid receptor coactivator-1 (SRC-1) by approximately 4-fold. Based on a docking study, for the first time, we propose a model of amentoflavone and hPPAR gamma binding in which amentoflavone forms three hydrogen bonds with the side chains of His323, Tyr327, and Arg280 in hPPAR gamma and participates in two hydrophobic interactions.