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Science 310 (5756): 1966-1970

Copyright © 2005 by the American Association for the Advancement of Science

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

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

Abstract: Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are two major inflammatory mediators. Here we show that iNOS specifically binds to COX-2 and S-nitrosylates it, enhancing COX-2 catalytic activity. Selectively disrupting iNOS–COX-2 binding prevented NO-mediated activation of COX-2. This synergistic molecular interaction between two inflammatory systems may inform the 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}

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