Research Article

The Structure of Nitric Oxide Synthase Oxygenase Domain and Inhibitor Complexes

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Science  17 Oct 1997:
Vol. 278, Issue 5337, pp. 425-431
DOI: 10.1126/science.278.5337.425

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Abstract

The nitric oxide synthase oxygenase domain (NOSox) oxidizes arginine to synthesize the cellular signal and defensive cytotoxin nitric oxide (NO). Crystal structures determined for cytokine-inducible NOSox reveal an unusual fold and heme environment for stabilization of activated oxygen intermediates key for catalysis. A winged β sheet engenders a curved α-β domain resembling a baseball catcher's mitt with heme clasped in the palm. The location of exposed hydrophobic residues and the results of mutational analysis place the dimer interface adjacent to the heme-binding pocket. Juxtaposed hydrophobic O2- and polarl-arginine–binding sites occupied by imidazole and aminoguanidine, respectively, provide a template for designing dual-function inhibitors and imply substrate-assisted catalysis.

  • * Present address: Beckman Institute, California Institute of Technology, Pasadena, CA 91125, USA.

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