<p>Nitric oxide synthase (<db_xref db="EC" dbkey="1.14.13.39"/>) (NOS) enzymes produce nitric oxide (NO) by catalysing 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 [<cite idref="PUB00007289"/>].</p><p>Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria [<cite idref="PUB00007289"/>]. 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) [<cite idref="PUB00007290"/>]. 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 haem-thiolate proteins, and a C-terminal reductase domain, which is homologous to NADPH:P450 reductase (<db_xref db="EC" dbkey="1.6.2.4"/>). 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 animal NOS isozymes are catalytically self-sufficient. The electron flow in the NO synthase reaction is: NADPH --> FAD --> FMN --> haem --> O(2).</p><p>eNOS localisation to endothelial membranes is mediated by cotranslational N-terminal myristoylation and post-translational palmitoylation [<cite idref="PUB00007291"/>]. The subcellular localisation of nNOS in skeletal muscle ismediated by anchoring of nNOS to dystrophin. nNOS contains an additional N-terminal domain, the PDZ domain [<cite idref="PUB00007292"/>]. Some bacteria, like <taxon tax_id="86665">Bacillus halodurans</taxon>, <taxon tax_id="1423">Bacillus subtilis</taxon> or <taxon tax_id="1299">Deinococcus radiodurans</taxon>, contain homologs of NOS oxygenase domain. The pattern is directed against the N-terminal haem binding site.</p><p>This entry represents the oxygenase domain of NOS.</p>
Nitric oxide synthase, oxygenase domain