Researchers have determined the structure of an enzyme that inactivates the nerve agent sarin and related toxic molecules. The results, published in the May issue of Nature Structural & Molecular Biology, provide insights into how the enzyme selects its targets and how this selectivity can be fine-tuned toward a particular set of targets.
Paraoxonase cleaves and inactivates toxic organophosphates such as sarin. It is also a component of the high-density lipoprotein particle (HDL, the 'good cholesterol') and its activity is involved in preventing the formation of fatty deposits on the artery walls. Paraoxonase is thus valuable from both antibioterrorism and medical perspectives. To understand how a single enzyme can act on such a broad spectrum of targets, Danny Tawfik and colleagues have determined the crystal structure of a mammalian paraoxonase. Structural and mutational analyses suggest the location of the active site and how the enzyme selects its targets. These results provide a basis for engineering the enzyme's activity toward a subset of its substrates for various biomedical applications.
Dan S. Tawfik
The Weizmann Institute of Science
Tel: +972 8 934 3637
Also available online.
(C) Nature Structural & Molecular Biology press release.
Message posted by: Trevor M. D'Souza