Update on Mechanism and Catalytic Regulation in the NO Synthases
Nitric-oxide synthases (NOSs, EC 1.14.13.39) 1 oxidize L-arginine to nitric oxide (NO) and are interesting for several reasons. They are present in many life forms (1, 2), their gene regulation is complex (3), they are the only flavoheme enzymes that utilize tetrahydrobiopterin (H 4 B) as a redox cofactor, and their electron transfer reactions are regulated by a Ca 2 -binding protein (calmodulin). In the past 5 years, crystal structures of NOS heme (oxygenase) domains and bacterial NOS-like proteins have shown how Arg, heme, and H 4 B bind in the active site (4, 5). Reviews are available on NOS biochemistry (6), regulation (7, 8), protein-protein interactions (9), and posttranslational modifications (10). This minireview updates the NO biosynthetic mechanism and describes a global catalytic model that highlights the role of NO as an intrinsic regulator.