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Inducible Nitric Oxide Synthase Binds, S-Nitrosylates, and Activates Cyclooxygenase-2
Sangwon F. Kim,1Daniel A. Huri,1Solomon 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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