Nitric Oxide Synthase Enzymology in the Twenty Years After the Nobel Prize.

This review briefly summarizes what was known about NO synthase (NOS) enzymology at the time of the Nobel prize award in 1998, and then discusses from the Author's perspective some of the advances in NOS enzymologic research over the subsequent twenty years, focused on five aspects: The maturation process of NOS enzymes and its regulation; the mechanism of NO synthesis; the redox roles played by the 6R-tetrahydrobiopterin cofactor; the role of protein conformational behavior in enabling NOS electron transfer and its regulation by NOS structural elements and calmodulin; and the catalytic cycling pathways of NOS enzymes, their regulation, and their influence on NOS activity.