title: Peroxisome proliferator-activated receptors (PPARs) have multiple binding points that accommodate ligands in various conformations: phenylpropanoic acid-type PPAR ligands bind to PPAR in different conformations, depending on the subtype.
abstract: Human peroxisome proliferator-activated receptors (hPPARs) are ligand-dependent transcription factors that control various biological responses, and there are three subtypes: hPPARα, hPPARδ, and hPPARγ. We report here that α-substituted phenylpropanoic acid-type hPPAR agonists with similar structure bind to the hPPAR ligand binding domain (LBD) in different conformations, depending on the receptor subtype. These results might indicate that hPPAR ligand binding pockets have multiple binding points that can be utilized to accommodate structurally flexible hPPAR ligands.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kuwabara
authors.forename: Takuji
authors.initials: T
authors.lastname: Oyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomioka
authors.forename: Masao
authors.initials: M
authors.lastname: Ohashi
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Miyachi
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D047493:PPAR alpha / Q000819:agonists* / Q000737:chemistry; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry; D010666:Phenylpropionates / Q000737:chemistry*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000819:agonists / Q000737:chemistry
chemical_list: D008024:Ligands; D047493:PPAR alpha; D047494:PPAR delta; D047495:PPAR gamma; D010666:Phenylpropionates; D011994:Recombinant Proteins; D000218:Adamantane