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The Structure of Nitric Oxide Synthase Oxygenase Domain and Inhibitor Complexes

Crane, Brian R. and Arvai, Andrew S. and Gachhui, Ratan and Wu, Chaoqun and Ghosh, Dipak K. and Getzoff, Elizabeth D. and Stuehr, Dennis J. and Tainer, John A. (1997) The Structure of Nitric Oxide Synthase Oxygenase Domain and Inhibitor Complexes. Science, 278 (5337). pp. 425-431. ISSN 0036-8075. https://resolver.caltech.edu/CaltechAUTHORS:20141203-134838104

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.278.5337.425DOIArticle
http://www.sciencemag.org/content/278/5337/425.fullPublisherArticle
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.
Funders:
Funding AgencyGrant Number
NIHHL58883
NIHCA53914
American Heart AssociationUNSPECIFIED
Issue or Number:5337
Record Number:CaltechAUTHORS:20141203-134838104
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20141203-134838104
Official Citation:The Structure of Nitric Oxide Synthase Oxygenase Domain and Inhibitor Complexes Brian R. Crane, Andrew S. Arvai, Ratan Gachhui, Chaoqun Wu, Dipak K. Ghosh, Elizabeth D. Getzoff, Dennis J. Stuehr, and John A. Tainer Science 17 October 1997: 278 (5337), 425-431. [DOI:10.1126/science.278.5337.425]
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52345
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:03 Dec 2014 21:56
Last Modified:03 Oct 2019 07:41

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