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

Academic Article

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, N5-(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.
  • Authors

    Published In

  • Biochemistry  Journal
  • Digital Object Identifier (doi)

    Author List

  • Li H; Raman CS; Mart├ísek P; Masters BSS; Poulos TL
  • Start Page

  • 5399
  • End Page

  • 5406
  • Volume

  • 40
  • Issue

  • 18