4YT1

Human PPAR Gamma Ligand Binding Domain in complex with a Gammma Selective Synthetic Partial Agonist MEKT76

Summary for 4YT1

• Entry DOI: 10.2210/pdb4yt1/pdb
• Descriptor: Peroxisome proliferator-activated receptor gamma, N-(benzylsulfonyl)-4-propoxy-3-({[4-(pyrimidin-2-yl)benzoyl]amino}methyl)benzamide (3 entities in total)
• Functional Keywords: nuclear receptor, transcription
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 65605.93

Authors

Oyama, T.,Ohashi, M.,Miyachi, H.,Kusunoki, M. (deposition date: 2015-03-17, release date: 2016-03-02, Last modification date: 2023-11-08)

Primary citation

Ohashi, M.,Gamo, K.,Oyama, T.,Miyachi, H.
Peroxisome proliferator-activated receptor gamma (PPAR gamma ) has multiple binding points that accommodate ligands in various conformations: Structurally similar PPAR gamma partial agonists bind to PPAR gamma LBD in different conformations
Bioorg.Med.Chem.Lett., 25:2758-2762, 2015

PubMed Abstract: In the course of studies directed toward the creation of human peroxisome proliferator-activated receptor gamma (hPPARγ) partial agonists, we designed and synthesized benzylsulfonylaminocarbonyl derivative (3) by structural modification of our reported hPPARγ partial agonist 2. Co-crystallization of 3 with the hPPARγ ligand-binding domain (LBD) afforded a homodimeric complex in which one of the LBDs adopts a fully active structure without bound 3, while the other LBD exhibits a non-fully active structure containing one molecule of bound 3. Interestingly, 2 and 3 are structurally similar, but bind to hPPARγ LBD in distinct conformations, that is, the sulfonylaminocarbonyl moiety of bound 3 is directed at 180° away from that of bound 2. These results support our previous proposal that the hPPARγ LBD has multiple binding points that can be utilized to accommodate structurally flexible hPPAR ligands.

PubMed: 26025876
DOI: 10.1016/j.bmcl.2015.05.025

Experimental method

X-RAY DIFFRACTION (2.2 Å)