Crystal structures of the ligand-binding domain of human peroxisome proliferator-activated receptor δ in complexes with phenylpropanoic acid derivatives and a pyridine carboxylic acid derivative

Peroxisome proliferator-activated receptor δ (PPAR δ ) is a member of the nuclear receptor family and regulates glucose and lipid homeostasis in a ligand-dependent manner. Numerous phenylpropanoic acid derivatives targeting three PPAR subtypes (PPAR α , PPAR γ and PPAR δ ) have been developed towards the treatment of serious diseases such as lipid-metabolism disorders. In spite of the increasing attraction of PPAR δ as a pharmaceutical target, only a limited number of protein – ligand complex structures are available. Here, four crystal structures of the ligand-binding domain of PPAR δ in complexes with phenylpropanoic acid derivatives and a pyridine carboxylic acid derivative are described, including an updated, higher resolution version of a previous studied structure and three novel structures. These structures showed that the ligands were bound in the ligand-binding pocket of the receptor in a similar manner but with minor variations. The results could provide variable structural information for the further design and development of ligands targeting PPAR δ .

Source: Acta Crystallographica Section F - January 31, 2022 Category: Biochemistry Authors: Oyama, T. Takiguchi, K. Miyachi, H. Tags: nuclear receptors peroxisome proliferator-activated receptor δ PPAR ligand-binding domain research communications Source Type: research