3HOD
Crystal structure of the PPARgamma-LBD complexed with a new aryloxy-3phenylpropanoic acid
Summary for 3HOD
| Entry DOI | 10.2210/pdb3hod/pdb |
| Related | 3B3K 3HO0 |
| Descriptor | Peroxisome proliferator-activated receptor gamma, (2S)-2-(4-benzylphenoxy)-3-phenylpropanoic acid (3 entities in total) |
| Functional Keywords | 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 |
| Biological source | Homo sapiens (Human) |
| Cellular location | Nucleus: P37231 |
| Total number of polymer chains | 2 |
| Total formula weight | 65393.70 |
| Authors | Pochetti, G.,Montanari, R.,Mazza, F.,Loiodice, F.,Fracchiolla, G.,Laghezza, A.,Lavecchia, A.,Novellino, E. (deposition date: 2009-06-02, release date: 2009-10-27, Last modification date: 2023-11-01) |
| Primary citation | 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 Cited by 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: 19775169DOI: 10.1021/jm900941b PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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