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Crystallographic studies on endothelial nitric oxide synthase complexed with nitric oxide and mechanism-based
1Departments of Molecular Biology & Biochemistry and Physiology & Biophysics and Program in Macromolecular Structure, University of California, Irvine 92697-3900, USA.
Abstract:
The crystal structure of the endothelial nitric oxide synthase (NOS) heme domain complexed with NO reveals close hydrogen bonding interactions between NO and the terminal guanidino nitrogen of the substrate, L-arginine. Dioxygen is expected to bind in a similar mode which will facilitate proton abstraction from L-Arg to dioxygen, a required step for O-O bond cleavage. Structures of mechanism-based NOS inhibitors, N(5)-(1-iminoethyl)-L-ornithine and N-(3-(aminomethyl)benzyl)acetamidine, provide clues on how this class of compounds operate as suicide substrate inhibitors leading to heme oxidation.