Work

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

Year: 2022

Type: article

Abstract: Peroxisome proliferator-activated receptor δ (PPARδ) 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 (PPARα, PPARγ and PPARδ) have been developed towards the treatment of serious diseases such as lipid-metabolism disorders. In spite of the increasing attraction of PPARδ 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 PPARδ 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 PPARδ.

Source: Acta Crystallographica Section F Structural Biology Communications

DOI: 10.1107/s2053230x22000449

Authors: Takuji Oyama, Kazuki Takiguchi, Hiroyuki Miyachi

Institutions: University of Yamanashi, The University of Tokyo

Language: English

Topic: Peroxisome Proliferator-Activated Receptors

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,100

Funders: Osaka University, Japan Science and Technology Agency, Institute for Protein Research, Osaka University, Adaptable and Seamless Technology Transfer Program through Target-Driven R and D