2YFE

Ligand binding domain of human PPAR gamma in complex with amorfrutin 1

Summary for 2YFE

• Entry DOI: 10.2210/pdb2yfe/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 3PRG 4PRG
• Descriptor: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA, Amorfrutin 1 (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: 66068.47

Authors

de Groot, J.C.,Buessow, K. (deposition date: 2011-04-05, release date: 2012-04-11, Last modification date: 2023-12-20)

Primary citation

Weidner, C.,De Groot, J.C.,Prasad, A.,Freiwald, A.,Quedenau, C.,Kliem, M.,Witzke, A.,Kodelja, V.,Han, C.-T.,Giegold, S.,Baumann, M.,Klebl, B.,Siems, K.,Mueller-Kuhrt, L.,Schuermann, A.,Schueller, R.,Pfeiffer, A.F.H.,Schroeder, F.C.,Buessow, K.,Sauer, S.
Amorfrutins are Potent Antidiabetic Dietary Natural Products
Proc.Natl.Acad.Sci.USA, 109:7257-, 2012

PubMed Abstract: Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.

PubMed: 22509006
DOI: 10.1073/PNAS.1116971109

Experimental method

X-RAY DIFFRACTION (2 Å)