4A4V

Ligand binding domain of human PPAR gamma in complex with amorfrutin 2

Summary for 4A4V

• Entry DOI: 10.2210/pdb4a4v/pdb
• Related: 1FM6 1FM9 1I7I 1K74 1KNU 1NYX 1PRG 1RDT 1WM0 1ZGY 2F4B 2FVJ 2G0G 2G0H 2PRG 2VSR 2VST 2VV0 2VV1 2VV2 2VV3 2VV4 2XKW 2YFE 3PRG 4A4W 4PRG
• Descriptor: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA, AMORFRUTIN 2 (3 entities in total)
• Functional Keywords: receptor, agonist, diabetes, insulin resistance
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Nucleus: P37231
• Total number of polymer chains: 2
• Total formula weight: 66000.44

Authors

de Groot, J.C.,Weidner, C.,Krausze, J.,Kawamoto, K.,Schroeder, F.C.,Sauer, S.,Buessow, K. (deposition date: 2011-10-20, release date: 2012-10-03, Last modification date: 2023-12-20)

Primary citation

De Groot, J.C.,Weidner, C.,Krausze, J.,Kawamoto, K.,Schroeder, F.C.,Sauer, S.,Bussow, K.
Structural Characterization of Amorfrutins Bound to the Peroxisome Proliferator-Activated Receptor Gamma.
J.Med.Chem., 56:1535-, 2013

PubMed Abstract: Amorfrutins are a family of natural products with high affinity to the peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor regulating lipid and glucose metabolism. The PPARγ agonist rosiglitazone increases insulin sensitivity and is effective against type II diabetes but has severe adverse effects including weight gain. Amorfrutins improve insulin sensitivity and dyslipidemia but do not enhance undesired fat storage. They bear potential as therapeutics or prophylactic dietary supplements. We identified amorfrutin B as a novel partial agonist of PPARγ with a considerably higher affinity than that of previously reported amorfrutins, similar to that of rosiglitazone. Crystal structures reveal the geranyl side chain of amorfrutin B as the cause of its particularly high affinity. Typical for partial agonists, amorfrutins 1, 2, and B bind helix H3 and the β-sheet of PPARγ but not helix H12.

PubMed: 23286787
DOI: 10.1021/JM3013272

Experimental method

X-RAY DIFFRACTION (2 Å)