How PPAR-gamma -- a fatty acid receptor that plays a central role in energy metabolism -- is activated by a natural ligand is revealed in a study online in Nature Structural & Molecular Biology. The findings could be useful in the design of better drugs to treat type 2 diabetes.
Dysfunctions in PPAR-gamma are linked to diabetes, cardiovascular disease and obesity, so the receptor is an important target for type 2 diabetes drugs. Previous work had shown that synthetic binding molecules, or ligands, activate PPAR-gamma by making contacts with one specific part of the protein. Yong Li, Eric Xu and colleagues now show that nitrated linoleic acid, a potent natural ligand, makes contacts with this same region but also with a second one, explaining how it is recognized by PPAR-gamma and why it has such high activity. Author contacts: H. Eric Xu (Van Andel Research Institute, Grand Rapids, MI, USA)
E-mail: eric.xu@vai.org Yong Li (University of Pittsburgh, Pittsburgh, PA, USA)
E-mail: yol21@pitt.edu Abstract available online. (C) Nature Structural & Molecular Biology press release.
Message posted by: Trevor M. D'Souza
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