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 Con
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- 作者：Naoyuki Kuwabara ; Takuji Oyama ; Daisuke Tomioka ; Masao Ohashi ; Junn Yanagisawa ; Toshiyuki Shimizu ; Hiroyuki Miyachi
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：January 26, 2012
- 年：2012
- 卷：55
- 期：2
- 页码：893-902
- 全文大小：633K
- 年卷期：v.55,no.2(January 26, 2012)
- ISSN：1520-4804
文摘
Human peroxisome proliferator-activated receptors (hPPARs) are ligand-dependent transcription factors that control various biological responses, and there are three subtypes: hPPAR伪, hPPAR未, and hPPAR纬. We report here that 伪-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.