Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2013 Feb 28;56(4):1535-43. doi: 10.1021/jm3013272. Epub 2013 Feb 6.

Structural characterization of amorfrutins bound to the peroxisome proliferator-activated receptor γ.

Author information

  • 1Department of Molecular Structural Biology, Helmholtz Centre for Infection Research, 38214 Braunschweig, Germany.

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.

PMID:
23286787
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk