The Structure of Nitric Oxide Synthase Oxygenase Domain and Inhibitor Complexes
Abstract
The nitric oxide synthase oxygenase domain (NOS_(ox)) oxidizes arginine to synthesize the cellular signal and defensive cytotoxin nitric oxide (NO). Crystal structures determined for cytokine-inducible NOS_(ox) 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 O_2- and polarL-arginine–binding sites occupied by imidazole and aminoguanidine, respectively, provide a template for designing dual-function inhibitors and imply substrate-assisted catalysis.
Additional Information
© 1997 American Association for the Advancement of Science. Received 20 August 1997; accepted 22 September 1997. We thank C. Mol, C. Putnam, A. Bilwes, and J. Noel for help with data collection, A. Bilwes and D. Goodin for helpful discussions, P. Clark, T. Macke, and J. Zhang for technical assistance, and SSRL for use of data collection facilities. Supported by NIH grants HL58883 and CA53914. D.J.S. is an Established Investigator of the American Heart Association.Additional details
- Eprint ID
- 52345
- Resolver ID
- CaltechAUTHORS:20141203-134838104
- HL58883
- NIH
- CA53914
- NIH
- American Heart Association
- Created
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2014-12-03Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field