|PROSITE documentation PDOC60001|
Nitric oxide synthase (EC 22.214.171.124) (NOS) enzymes produce nitric oxide (NO) by catalyzing a five-electron oxidation of a guanidino nitrogen of L-arginine (L-Arg). Oxidation of L-Arg to L-citrulline occurs via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine as an intermediate. 2 mol of O(2) and 1.5 mol of NADPH are consumed per mole of NO formed .
Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria . Best studied are mammals, where three distinct genes encode NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) . iNOS and nNOS are soluble and found predominantly in the cytosol, while eNOS is membrane associated. The enzymes exist as homodimers, each monomer consisting of two major domains: an N-terminal oxygenase domain, which belongs to the class of heme-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (EC 126.96.36.199). The interdomain linker between the oxygenase and reductase domains contains a calmodulin (CaM)-binding sequence. NOSs are the only enzymes known to simultaneously require five bound cofactors/prosthetic groups: FAD, FMN, heme, tetrahydrobiopterin and Ca2+-CaM. The animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH --> FAD --> FMN --> heme --> O(2).
eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation (see <PDOC00008>) and post-translational palmitoylation . The subcellular localisation of nNOS in skeletal muscle is mediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain (see <PDOC50106>) .
Some bacteria, like Bacillus halodurans, Bacillus subtilis or Deinococcus radiodurans, contain homologs of NOS oxygenase domain.
The pattern is directed against the N-terminal heme binding site.Expert(s) to contact by email:
December 2001 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Liu Q. Gross S.S.|
|Title||Binding sites of nitric oxide synthases.|
|Source||Methods Enzymol. 268:311-324(1996).|
|2||Authors||Knowles R.G. Moncada S.|
|Title||Nitric oxide synthases in mammals.|
|Source||Biochem. J. 298:249-258(1994).|
|3||Authors||Liu J. Hughes T.E. Sessa W.C.|
|Title||The first 35 amino acids and fatty acylation sites determine the molecular targeting of endothelial nitric oxide synthase into the Golgi region of cells: a green fluorescent protein study.|
|Source||J. Cell Biol. 137:1525-1535(1997).|
|4||Authors||Ponting C.P. Phillips C.|
|Title||DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins.|
|Source||Trends Biochem. Sci. 20:102-103(1995).|