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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 (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 t...

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Autores principales: Oyama, Takuji, Takiguchi, Kazuki, Miyachi, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805212/
https://www.ncbi.nlm.nih.gov/pubmed/35102897
http://dx.doi.org/10.1107/S2053230X22000449
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author Oyama, Takuji
Takiguchi, Kazuki
Miyachi, Hiroyuki
author_facet Oyama, Takuji
Takiguchi, Kazuki
Miyachi, Hiroyuki
author_sort Oyama, Takuji
collection PubMed
description 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.
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spelling pubmed-88052122022-02-09 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 Oyama, Takuji Takiguchi, Kazuki Miyachi, Hiroyuki Acta Crystallogr F Struct Biol Commun Research Communications 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. International Union of Crystallography 2022-01-31 /pmc/articles/PMC8805212/ /pubmed/35102897 http://dx.doi.org/10.1107/S2053230X22000449 Text en © Takuji Oyama et al. 2022 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
spellingShingle Research Communications
Oyama, Takuji
Takiguchi, Kazuki
Miyachi, Hiroyuki
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805212/
https://www.ncbi.nlm.nih.gov/pubmed/35102897
http://dx.doi.org/10.1107/S2053230X22000449
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