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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.

Pubmed ID: 16373578

Authors

  • Kim SF
  • Huri DA
  • Snyder SH

Journal

Science (New York, N.Y.)

Publication Data

December 23, 2005

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA000266
  • Agency: NIDA NIH HHS, Id: DA00074

Mesh Terms

  • Animals
  • Biotin
  • Catalysis
  • Cell Line
  • Cyclooxygenase 2
  • Cysteine
  • Dinoprostone
  • Enzyme Activation
  • Humans
  • Mice
  • Nitric Oxide Donors
  • Nitric Oxide Synthase Type II
  • Nitroso Compounds
  • Protein Binding
  • S-Nitrosoglutathione