Citation

Li H, Raman CS, Martásek P, Masters BS, Poulos TL. Biochemistry 2001; 40(18): 5399-5406.

Copyright

(Copyright © 2001, American Chemical Society)

DOI

10.1021/bi002658v

PMID

11331003

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.

Language: en

Keywords

Amidines; Animals; Benzylamines; Binding, Competitive; Cattle; Crystallography, X-Ray; Enzyme Inhibitors; Ferrous Compounds; Heme; Isoenzymes; Macromolecular Substances; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Ornithine; Protein Structure, Tertiary