Nitric oxide synthase (NOS) eukaryotic oxygenase domain. NOS produces nitric oxide (NO) by catalyzing a five-electron heme-based oxidation of a guanidine nitrogen of L-arginine to L-citrulline via two successive monooxygenation reactions producing N(omega)-hydroxy-L-arginine (NHA) as an intermediate. In mammals, there are three distinct NOS isozymes: neuronal (nNOS or NOS-1), cytokine-inducible (iNOS or NOS-2) and endothelial (eNOS or NOS-3) . Nitric oxide synthases are homodimers. In eukaryotes, each monomer has an N-terminal oxygenase domain, which binds to the substrate L-Arg, zinc, and to the cofactors heme and 5.6.7.8-(6R)-tetrahydrobiopterin (BH4) . Eukaryotic NOS's also have a C-terminal electron supplying reductase region, which is homologous to cytochrome P450 reductase and binds NADH, FAD and FMN.
Structure:1M8E_A, murine iNOS with inhibitor 7-Nitroindazole bound in place of L-Arg (displacing side chain of a glutamate residue), heme, and tetrahydrobiopterin
Jiyao W et al.(2023). "The conserved domain database in 2023.",