Inducible nitric oxide synthase binds, S-nitrosylates, and activates cyclooxygenase-2.
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.
Kim
Sangwon F
SF
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Huri
Daniel A
DA
Snyder
Solomon H
SH
D000818:Animals; D001710:Biotin / Q000378:metabolism; D002384:Catalysis; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D020030:Nitric Oxide Donors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism*; D011485:Protein Binding; D026422:S-Nitrosoglutathione / Q000378:metabolism
D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D026422:S-Nitrosoglutathione; D001710:Biotin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D003545:Cysteine