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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5337
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pubmed:dateCreated |
1997-11-5
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/5,6,7,8-tetrahydrobiopterin,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Biopterin,
http://linkedlifedata.com/resource/pubmed/chemical/Caenorhabditis elegans Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanidines,
http://linkedlifedata.com/resource/pubmed/chemical/Heme,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygenases,
http://linkedlifedata.com/resource/pubmed/chemical/imidazole,
http://linkedlifedata.com/resource/pubmed/chemical/pimagedine
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0036-8075
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
425-31
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9334294-Amino Acid Sequence,
pubmed-meshheading:9334294-Arginine,
pubmed-meshheading:9334294-Binding Sites,
pubmed-meshheading:9334294-Biopterin,
pubmed-meshheading:9334294-Caenorhabditis elegans Proteins,
pubmed-meshheading:9334294-Catalysis,
pubmed-meshheading:9334294-Crystallography, X-Ray,
pubmed-meshheading:9334294-Dimerization,
pubmed-meshheading:9334294-Enzyme Induction,
pubmed-meshheading:9334294-Enzyme Inhibitors,
pubmed-meshheading:9334294-Guanidines,
pubmed-meshheading:9334294-Heme,
pubmed-meshheading:9334294-Homeodomain Proteins,
pubmed-meshheading:9334294-Hydrogen Bonding,
pubmed-meshheading:9334294-Imidazoles,
pubmed-meshheading:9334294-Isoenzymes,
pubmed-meshheading:9334294-Models, Molecular,
pubmed-meshheading:9334294-Molecular Sequence Data,
pubmed-meshheading:9334294-Nitric Oxide Synthase,
pubmed-meshheading:9334294-Oxidation-Reduction,
pubmed-meshheading:9334294-Oxygen,
pubmed-meshheading:9334294-Oxygenases,
pubmed-meshheading:9334294-Protein Conformation,
pubmed-meshheading:9334294-Protein Folding,
pubmed-meshheading:9334294-Protein Structure, Secondary
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pubmed:year |
1997
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pubmed:articleTitle |
The structure of nitric oxide synthase oxygenase domain and inhibitor complexes.
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pubmed:affiliation |
Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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