Crystallographic studies on endothelial nitric oxide synthase complexed with nitric oxide and mechanism-based inhibitors

The crystal structure of the endothelial nitric oxide synthase (NOS) heme d omain complexed with NO reveals close hydrogen bonding interactions between NO and the terminal guanidino nitrogen of the substrate, L-arginine. Dioxy gen is expected to bind in a similar mode which will facilitate proton abst raction from L-Arg to dioxygen, a required step for O-O bond cleavage. Stru ctures of mechanism-based NOS inhibitors, N-5-(1-iminoethyl)-L-ornithine an d N-(3-(aminomethyl)benzyl)acetamidine, provide clues on how this class of compounds operate as suicide substrate inhibitors leading to heme oxidation .