Ligand and receptor dynamics contribute to the mechanism of graded PPARγ agonism.

ABSTRACT: Ligand binding to proteins is not a static process, but rather involves a number of complex dynamic transitions. A flexible ligand can change conformation upon binding its target. The conformation and dynamics of a protein can change to facilitate ligand binding. The conformation of the ligand, however, is generally presumed to have one primary binding mode, shifting the protein conformational ensemble from one state to another. We report solution nuclear magnetic resonance (NMR) studies that reveal peroxisome proliferator-activated receptor γ (PPARγ) modulators can sample multiple binding modes manifesting in multiple receptor conformations in slow conformational exchange. Our NMR, hydrogen/deuterium exchange and docking studies reveal that ligand-induced receptor stabilization and bindin

SUBMITTER: Hughes TS 

PROVIDER: S-EPMC3278220 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature