Three nitric-oxide synthase (NOS) isozymes play crucial, but distinct, roles in
neurotransmission, vascular homeostasis, and host defense, by catalyzing Ca
2+/calmodulin-triggered NO synthesis. Here, we address current questions regarding NOS
activity and regulation by combining mutagenesis and biochemistry with crystal structure
determination of a fully assembled, electron-supplying, neuronal NOS reductase dimer. By
integrating these results, we structurally elucidate the unique mechanisms for isozyme …