3LMP

Crystal structure of the PPARgamma-LBD complexed with a cercosporamide derivative modulator

Summary for 3LMP

• Entry DOI: 10.2210/pdb3lmp/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, Peptide of Nuclear receptor coactivator 1, (9aS)-8-acetyl-1,7-dihydroxy-3-methoxy-9a-methyl-N-(1-naphthylmethyl)-9-oxo-9,9a-dihydrodibenzo[b,d]furan-4-carboxamide, ... (4 entities in total)
• Functional Keywords: three-layered alpha-helical sandwich, activator, alternative splicing, diabetes mellitus, disease mutation, dna-binding, metal-binding, nucleus, obesity, phosphoprotein, polymorphism, receptor, transcription, transcription regulation, zinc-finger
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P37231 Q15788
• Total number of polymer chains: 2
• Total formula weight: 34674.13

Authors

Matsui, Y.,Hanzawa, H. (deposition date: 2010-01-31, release date: 2010-04-14, Last modification date: 2023-11-01)

Primary citation

Furukawa, A.,Arita, T.,Satoh, S.,Wakabayashi, K.,Hayashi, S.,Matsui, Y.,Araki, K.,Kuroha, M.,Ohsumi, J.
Discovery of a novel selective PPARgamma modulator from (-)-Cercosporamide derivatives
Bioorg.Med.Chem.Lett., 20:2095-2098, 2010

PubMed Abstract: In an investigation of (-)-Cercosporamide derivatives with a plasma glucose-lowering effect, we found that N-benzylcarboxamide derivative 4 was a partial agonist of PPARgamma. A SAR study of the substituents on carboxamide nitrogen afforded the N-(1-naphthyl)methylcarboxamide derivative 23 as the most potent selective PPARgamma modulator. An X-ray crystallography study revealed that compound 23 bounded to the PPARgamma ligand binding domain in a unique way without any interaction with helix12. Compound 23 displayed a potent plasma glucose-lowering effect in db/db mice without the undesirable increase in body fluid and heart weight that is typically observed when PPARgamma full agonists are administrated.

PubMed: 20219371
DOI: 10.1016/j.bmcl.2010.02.073

Experimental method

X-RAY DIFFRACTION (1.9 Å)