title: Crystallographic studies on endothelial nitric oxide synthase complexed with nitric oxide and mechanism-based inhibitors.
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.
authors.affiliation: Departments of Molecular Biology & Biochemistry and Physiology & Biophysics and Program in Macromolecular Structure, University of California, Irvine 92697-3900, USA.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: C S
authors.initials: CS
authors.lastname: Raman
authors.forename: P
authors.initials: P
authors.lastname: Martásek
authors.forename: B S
authors.initials: BS
authors.lastname: Masters
authors.forename: T L
authors.initials: TL
authors.lastname: Poulos
mesh_terms: D000578:Amidines / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000737:chemistry / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D005296:Ferrous Compounds / Q000737:chemistry; D006418:Heme / Q000737:chemistry; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances; D009569:Nitric Oxide / Q000737:chemistry* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009952:Ornithine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary
chemical_list: D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D007527:Isoenzymes; D046911:Macromolecular Substances; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D006418:Heme; D009952:Ornithine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III