7EFQ

Crystal structure of hPPARgamma ligand binding domain complexed with rosiglitazone-based fluorescence probe

Summary for 7EFQ

• Entry DOI: 10.2210/pdb7efq/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, (5S)-5-[[4-[2-[[7-(diethylamino)-2-oxidanylidene-chromen-4-yl]-methyl-amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione (3 entities in total)
• Functional Keywords: ppargamma, rosiglitazone, coumarin, fluorescence probe, tzd, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 63394.63

Authors

Yoshikawa, C.,Ishida, H.,Ohashi, N.,Itoh, T. (deposition date: 2021-03-23, release date: 2021-05-12, Last modification date: 2023-11-29)

Primary citation

Yoshikawa, C.,Ishida, H.,Ohashi, N.,Itoh, T.
Synthesis of a Coumarin-Based PPAR gamma Fluorescence Probe for Competitive Binding Assay.
Int J Mol Sci, 22:-, 2021

PubMed Abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is a molecular target of metabolic syndrome and inflammatory disease. PPARγ is an important nuclear receptor and numerous PPARγ ligands were developed to date; thus, efficient assay methods are important. Here, we investigated the incorporation of 7-diethylamino coumarin into the PPARγ agonist rosiglitazone and used the compound in a binding assay for PPARγ. PPARγ-ligand-incorporated 7-methoxycoumarin, , showed weak fluorescence intensity in a previous report. We synthesized PPARγ-ligand-incorporating coumarin, , in this report, and it enhanced the fluorescence intensity. The PPARγ ligand maintained the rosiglitazone activity. The obtained partial agonist appeared to act through a novel mechanism. The fluorescence intensity of and increased by binding to the ligand binding domain (LBD) of PPARγ and the affinity of reported PPARγ ligands were evaluated using the probe.

PubMed: 33919837
DOI: 10.3390/ijms22084034

Experimental method

X-RAY DIFFRACTION (2.3 Å)