Publication Date:
1997-10-23
Description:
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 beta sheet engenders a curved alpha-beta 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 polar L-arginine-binding sites occupied by imidazole and aminoguanidine, respectively, provide a template for designing dual-function inhibitors and imply substrate-assisted catalysis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crane, B R -- Arvai, A S -- Gachhui, R -- Wu, C -- Ghosh, D K -- Getzoff, E D -- Stuehr, D J -- Tainer, J A -- CA53914/CA/NCI NIH HHS/ -- HL58883/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 1997 Oct 17;278(5337):425-31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9334294" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Arginine/chemistry/metabolism
;
Binding Sites
;
Biopterin/analogs & derivatives/metabolism
;
*Caenorhabditis elegans Proteins
;
Catalysis
;
Crystallography, X-Ray
;
Dimerization
;
Enzyme Induction
;
Enzyme Inhibitors/metabolism
;
Guanidines/metabolism
;
Heme/chemistry
;
Homeodomain Proteins/chemistry/*genetics/physiology
;
Hydrogen Bonding
;
Imidazoles/metabolism
;
Isoenzymes/antagonists & inhibitors/*chemistry/metabolism
;
Models, Molecular
;
Molecular Sequence Data
;
Nitric Oxide Synthase/antagonists & inhibitors/*chemistry/metabolism
;
Oxidation-Reduction
;
Oxygen/metabolism
;
Oxygenases/chemistry/metabolism
;
*Protein Conformation
;
Protein Folding
;
Protein Structure, Secondary
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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