3CDP

Crystal structure of PPAR-gamma LBD complexed with a partial agonist, analogue of clofibric acid

Summary for 3CDP

• Entry DOI: 10.2210/pdb3cdp/pdb
• Related: 1K74 3CDS
• Descriptor: Peroxisome proliferator-activated receptor gamma, (2S)-2-(4-chlorophenoxy)-3-phenylpropanoic acid (3 entities in total)
• Functional Keywords: bundle of alpha-helices and a small four-stranded beta-sheet, activator, diabetes mellitus, disease mutation, dna-binding, metal-binding, nucleus, obesity, phosphoprotein, receptor, transcription, transcription regulation, zinc-finger
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 65338.02

Authors

Pochetti, G.,Montanari, R.,Mazza, F. (deposition date: 2008-02-27, release date: 2009-01-13, Last modification date: 2024-03-13)

Primary citation

Fracchiolla, G.,Laghezza, A.,Piemontese, L.,Parente, M.,Lavecchia, A.,Pochetti, G.,Montanari, R.,Di Giovanni, C.,Carbonara, G.,Tortorella, P.,Novellino, E.,Loiodice, F.
Synthesis, biological evaluation and molecular investigation of fluorinated peroxisome proliferator-activated receptors alpha/gamma dual agonists
Bioorg.Med.Chem., 20:2141-2151, 2012

PubMed Abstract: PPARs are transcription factors that govern lipid and glucose homeostasis and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new agonists for these receptors. Given that the introduction of fluorine generally has a profound effect on the physical and/or biological properties of the target molecule, we synthesized a series of fluorinated analogs of the previously reported compound 2, some of which turned out to be remarkable PPARα and PPARγ dual agonists. Docking experiments were also carried out to gain insight into the interactions of the most active derivatives with both receptors.

PubMed: 22341573
DOI: 10.1016/j.bmc.2012.01.025

Experimental method

X-RAY DIFFRACTION (2.8 Å)