The NOS homodimer is shown with the N-terminal oxygenase domain of each monomer in gray and the C-terminal reductase domain in beige. Cofactors in their oxidized state are shown in the left hand monomer, and reduced cofactors are shown on the right. Substrates O2 and arginine bind at or in close proximity to the heme iron. The conversion to products NO and citrulline is a multi-step process involving at least one distinct intermediate, N-hydroxy arginine. Electron flow proceeds from NADPH through the flavin nucleotides (purple) of the reductase domain to the heme (red) on the other monomer. It is unclear whether BH4 (green) participates as an active component of the electron transport chain. A zinc atom is tetrahedrally coordinated to 2 cysteines from each subunit in the active dimer. Four calcium ions (red) are shown coordinated to Calmodulin (CaM) at a bridge point between the oxygenase and reductase domains. The dimer interface occurs at large portions of the oxygenase domain of the monomers and involves BH4, Ca2+/CaM, and Zn as active stabilizing molecules.