title: Binding of intermediate, product, and substrate analogs to neuronal nitric oxide synthase: ferriheme is sensitive to ligand-specific effects in the L-arginine binding site.
abstract: The electron paramagnetic resonance spectra of purified neuronal nitric oxide synthase indicates that the binding of ligands to the arginine site perturbs the environment of the high-spin ferriheme in a highly ligand-specific manner. Four categories of high-spin complex can be distinguished; all are five-coordinate, and all retain the axial thiolate ligand, but they differ in their ligation geometries. These spectroscopic species reveal distinct local conformations which can be stabilized individually by the binding of L-arginine, N omega-hydroxy-L-arginine, N omega-methyl-L-arginine, and N omega-nitro-L-arginine. Other arginine analog inhibitors stabilize one or more of these states, revealing patterns based on the nature of substituents at the terminal amino group.
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Salerno
authors.forename: K
authors.initials: K
authors.lastname: McMillan
authors.forename: B S
authors.initials: BS
authors.lastname: Masters
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D002460:Cell Line; D002956:Citrulline / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D007668:Kidney; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D019335:Nitroarginine; D009952:Ornithine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D019323:omega-N-Methylarginine
chemical_list: D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D002956:Citrulline; C065027:N(G)-iminoethylornithine; C007985:N(5)-hydroxy-L-arginine; D006418:Heme; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase