3HOD

Crystal structure of the PPARgamma-LBD complexed with a new aryloxy-3phenylpropanoic acid

3HOD の概要

• エントリーDOI: 10.2210/pdb3hod/pdb
• 関連するPDBエントリー: 3B3K 3HO0
• 分子名称: Peroxisome proliferator-activated receptor gamma, (2S)-2-(4-benzylphenoxy)-3-phenylpropanoic acid (3 entities in total)
• 機能のキーワード: bundle of alpha-helices, small four-stranded beta-sheet, transcription, activator, alternative splicing, diabetes mellitus, disease mutation, dna-binding, metal-binding, nucleus, obesity, phosphoprotein, polymorphism, receptor, transcription regulation, zinc, zinc-finger
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Nucleus: P37231
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65393.70

構造登録者

Pochetti, G.,Montanari, R.,Mazza, F.,Loiodice, F.,Fracchiolla, G.,Laghezza, A.,Lavecchia, A.,Novellino, E. (登録日: 2009-06-02, 公開日: 2009-10-27, 最終更新日: 2023-11-01)

主引用文献

Fracchiolla, G.,Laghezza, A.,Piemontese, L.,Tortorella, P.,Mazza, F.,Montanari, R.,Pochetti, G.,Lavecchia, A.,Novellino, E.,Pierno, S.,Conte Camerino, D.,Loiodice, F.
New 2-Aryloxy-3-phenyl-propanoic Acids As Peroxisome Proliferator-Activated Receptors alpha/gamma Dual Agonists with Improved Potency and Reduced Adverse Effects on Skeletal Muscle Function
J.Med.Chem., 52:6382-6393, 2009

PubMed Abstract: The preparation of a new series of 2-aryloxy-3-phenyl-propanoic acids, resulting from the introduction of a linker into the diphenyl system of the previously reported PPARalpha/gamma dual agonist 1, allowed the identification of new ligands with improved potency on PPARalpha and unchanged activity on PPARgamma. For the most interesting stereoisomers S-2 and S-4, X-ray studies in PPARgamma and docking experiments in PPARalpha provided a molecular explanation for their different behavior as full and partial agonists of PPARalpha and PPARgamma, respectively. Due to the adverse effects provoked by hypolipidemic drugs on skeletal muscle function, we also investigated the blocking activity of S-2 and S-4 on skeletal muscle membrane chloride channel conductance and found that these ligands have a pharmacological profile more beneficial compared to fibrates currently used in therapy.

PubMed: 19775169
DOI: 10.1021/jm900941b

実験手法

X-RAY DIFFRACTION (2.1 Å)