Inducible Nitric Oxide Synthase Binds, S-Nitrosylates, and Activates Cyclooxygenase-2

doi:10.1126/science.1119407

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Science 23 December 2005:
Vol. 310. no. 5756, pp. 1966 - 1970
DOI: 10.1126/science.1119407

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Inducible Nitric Oxide Synthase Binds, S-Nitrosylates, and Activates Cyclooxygenase-2

Sangwon F. Kim,¹ Daniel A. Huri,¹ Solomon H. Snyder¹^,2^,3^*

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase(iNOS) are two major inflammatory mediators. Here we show thatiNOS specifically binds to COX-2 and S-nitrosylates it, enhancingCOX-2 catalytic activity. Selectively disrupting iNOS–COX-2binding prevented NO-mediated activation of COX-2. This synergisticmolecular interaction between two inflammatory systems may informthe development of anti-inflammatory drugs.

¹ Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
² Department of pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
³ Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.

^* To whom correspondence should be addressed. E-mail: ssnyder{at}jhmi.edu

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