NOS1 Background Information Nitric oxide (NO) has a broad range of biological activities and has been implicated in signaling pathways in phylogenetically diverse species. Nitric oxide synthases (NOSs), the enzymes responsible for synthesis of NO, contain an N-terminal oxygenase domain and a C-terminal reductase domain. NOS activity requires homodimerization as well as three cosubstrates (L-arginine, NADPH and O2) and five cofactors or prosthetic groups (FAD, FMN, heme, calmodulin and tetrahydrobiopterin). Several distinct NOS isoforms have been described and been shown to represent the products of three distinct genes. These include two constitutive Ca++/CaM-dependent forms of NOS, including ncNOS (also designated NOS1) whose activity was first identified in neurons, and ecNOS (also designated NOS3), first identified in endothelial cells. The inducible form of NOS, iNOS (also designated NOS2), is Ca++-independent and is expressed in a broad range of cell types. CaM kinase II alpha (CaMKIIa) can directly phosphorylate NOS1 on Ser 847, leading to a reduction of NOS1 activity in cells.
