52/nNOS/NOS Type I
Nitric oxide synthase (NOS) is a cell-type specific enzyme which catalyzes the synthesis of nitric oxide (NO). NO is a short-lived radical which transmits cellular signals involved in vasorelaxation, neurotransmission, and cytotoxicity. In neurons and endothelial cells, constitutive NOS (cNOS) is activated by agonists that increase intracellular Ca2+concentrations and enhance calmodulin binding. Neuronal NOS (nNOS or bNOS) and endothelial NOS (eNOS) have recognition sites for NADPH, FAD, FMN, and calmodulin and are regulated in a similar manner. However, both have been shown to be distinct gene products of about 155kDa and 140kDa, respectively, and the human forms show 52% amino acid identity to each other. nNOS and the 130 kDa inducible macrophage NOS (iNOS) share 51% amino acid homology. nNOS (neuronal NOS) is found in the cytoplasm of cell types such as neurons, skeletal muscle fibers, and lung epithelium. It is slightly larger than the other isoforms due to an N-terminal extension containing a PDZ domain through which it binds PSD-95 (post-synaptic density protein) and localizes to the cell membrane of synapses.