Research Highlights

Nature 455, 1152 (30 October 2008) | doi:10.1038/4551152d; Published online 29 October 2008

Chemical biology: NO problem

Nature Chem. Biol. doi:10.1038/nchembio.115 (2008)

Nitric oxide (NO) is involved in a host of mammalian signalling pathways, and several enzymes are charged with its synthesis. The overactivity of iNOS, one of these enzymes, has been linked to multiple sclerosis and Alzheimer's disease. Now researchers have found a way to inhibit it.

Elsa Garcin and Elizabeth Getzoff at the Scripps Research Institue in La Jolla, California, and their colleagues reasoned that the best approach to selectively block the action of this enzyme would be to study the structures of two drugs that preferentially hinder iNOS over other NO-producing enzymes. They then designed a new iNOS inhibitor that anchors itself to a binding pocket on the enzyme before inducing a cascade of conformational changes that make the inhibitor's grip more secure.