3QT0

Revealing a steroid receptor ligand as a unique PPARgamma agonist

Summary for 3QT0

• Entry DOI: 10.2210/pdb3qt0/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, Nuclear receptor coactivator 1 peptide, 11-(4-DIMETHYLAMINO-PHENYL)-17-HYDROXY-13-METHYL-17-PROP-1-YNYL-1,2,6,7,8,11,12,13,14,15,16,17-DODEC AHYDRO-CYCLOPENTA[A]PHENANTHREN-3-ONE, ... (4 entities in total)
• Functional Keywords: ppar gamma lbd domain, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P37231; Nucleus (By similarity): Q15788
• Total number of polymer chains: 2
• Total formula weight: 33331.80

Authors

Rong, H. (deposition date: 2011-02-22, release date: 2012-02-29, Last modification date: 2024-02-21)

Primary citation

Lin, S.,Han, Y.,Shi, Y.,Rong, H.,Zheng, S.,Jin, S.,Lin, S.Y.,Lin, S.C.,Li, Y.
Revealing a steroid receptor ligand as a unique PPAR gamma agonist.
Cell Res., 22:746-756, 2012

PubMed Abstract: Peroxisome proliferator-activated receptor gamma (PPARγ) regulates metabolic homeostasis and is a molecular target for anti-diabetic drugs. We report here the identification of a steroid receptor ligand, RU-486, as an unexpected PPARγ agonist, thereby uncovering a novel signaling route for this steroid drug. Similar to rosiglitazone, RU-486 modulates the expression of key PPARγ target genes and promotes adipocyte differentiation, but with a lower adipogenic activity. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for RU-486 in the PPARγ ligand-binding pocket with distinctive properties and epitopes, providing the molecular mechanisms for the discrimination of RU-486 from thiazolidinediones (TZDs) drugs. Our findings together indicate that steroid compounds may represent an alternative approach for designing non-TZD PPARγ ligands in the treatment of insulin resistance.

PubMed: 21986665
DOI: 10.1038/cr.2011.162

Experimental method

X-RAY DIFFRACTION (2.496 Å)