Fig. 1
Schematic eNOS homodimer structure with two monomers orientated "head-to-tail". Each monomer consists of a C-terminal reductase domain that binds NADPH, FAD, and FMN, a central calmodulin-binding region, and an N-terminal oxygenase domain that binds substrate L-Arg, oxygen, heme, and BH4. The formation of a homodimer enables the transfer of electrons from the reductase domain of one monomer to the oxygenase domain of the second monomer. The dimeric structure is stabilized by heme binding and by zinc ion in the zinc-thiolate cluster at the dimer interface. During catalysis, electrons from NADPH flow through the flavins FAD and FMN to the heme of the opposite monomer and CaM increases the rate of interdomain electron transfer. Heme reduction enables O2 binding, and BH4 can donate an electron to reduce and activate O2. When cellular redox balance is maintained, and the substrate L-Arg and the essential cofactor BH4 availabilities are optimal, O2 reduction is coupled to L-Arg oxidation and NO synthesis. L-Cit is formed as a byproduct