Nitric oxide synthases in GtoPdb v.2023.1

Nitric oxide synthases (NOS, E.C. 1.14.13.39) are a family of oxidoreductases that synthesize nitric (NO.) via the NADPH and oxygen-dependent consumption L-arginine with resultant by-product, L-citrulline. There 3 NOS isoforms they related by their capacity to produce NO, highly conserved organization functional domains significant homology at amino acid level. functionally distinguished cell type where expressed, intracellular targeting transcriptional post-translation mechanisms regulating enzyme activity. The nomenclature suggested NC-IUPHAR I, II III [12] has not gained wide acceptance, more commonly referred as neuronal (nNOS), inducible (iNOS) endothelial (eNOS) which reflect location expression (nNOS eNOS) (iNOS). All dimeric enzymes shuttle electrons from NADPH, binds C-terminal reductase domain, through flavins FAD FMN oxygenase domain other monomer enable BH4-dependent reduction heme bound oxygen for insertion into substrate, L-arginine. Electron flow is controlled calmodulin binding canonical motif located between these domains. eNOS nNOS activated concentrations calcium greater than 100 nM, while iNOS shows higher affinity Ca2+/calmodulin great avidity essentially calcium-independent constitutively active. Efficient stimulus-dependent coupling achieved subcellular respective N-terminal PDZ fatty acylation whereas largely cytosolic function independent location. primarily expressed in brain tissue, immune cells such macrophages layer vasculature although exceptions have been documented. L-NAME modified arginine analogues inhibitors all three isoforms, IC50 values micromolar range.