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PROSITE documentation PDOC60001 [for PROSITE entry PS60001]

Nitric oxide synthase (NOS) signature





Description

Nitric oxide synthase (EC 1.14.13.39) (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 [1].

Arginine-derived NO synthesis has been identified in mammals, fish, birds, invertebrates, plants, and bacteria [1]. 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) [2]. 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 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/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 [3]. 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>) [4].

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.

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html --------------------------------------------------------------------------------.

Expert(s) to contact by email:

Degtyarenko K.N.

Last update:

December 2001 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

NOS, PS60001; Nitric oxide synthase (NOS) signature  (PATTERN)


References

1AuthorsLiu Q. Gross S.S.
TitleBinding sites of nitric oxide synthases.
SourceMethods Enzymol. 268:311-324(1996).
PubMed ID8782597

2AuthorsKnowles R.G. Moncada S.
TitleNitric oxide synthases in mammals.
SourceBiochem. J. 298:249-258(1994).
PubMed ID7510950

3AuthorsLiu J. Hughes T.E. Sessa W.C.
TitleThe 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.
SourceJ. Cell Biol. 137:1525-1535(1997).
PubMed ID9199168

4AuthorsPonting C.P. Phillips C.
TitleDHR domains in syntrophins, neuronal NO synthases and other intracellular proteins.
SourceTrends Biochem. Sci. 20:102-103(1995).
PubMed ID7535955



PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.

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