title: Neuronal nitric oxide synthase, a modular enzyme formed by convergent evolution: structure studies of a cysteine thiolate-liganded heme protein that hydroxylates L-arginine to produce NO. as a cellular signal.
abstract: The nitric oxide synthases (NOS-I, neuronal, NOS-II, inducible, and NOS-III, endothelial) are the most recent additions to the large number of heme proteins that contain cysteine thiolate-liganded protoporphyrin IX heme prosthetic groups. This group of oxygenating enzymes also includes one of the largest gene families, that of the cytochromes P450, which have been demonstrated to be involved in the hydroxylation of a variety of substrates, including endogenous compounds (steroids, fatty acids, and prostaglandins) and exogenous compounds (therapeutic drugs, environmental toxicants, and carcinogens). The substrates for cytochromes P450 are universally hydrophobic while the physiological substrate for the nitric oxide synthases is the amino acid L-arginine, a hydrophilic compound. This review will discuss the approaches being used to study the structure and mechanism of neuronal nitric oxide synthase in the context of its known prosthetic groups and regulation by Ca(2+)-calmodulin and/or tetrahydrobiopterin (BH4).
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio 78284-7760, USA.
authors.forename: B S
authors.initials: BS
authors.lastname: Masters
authors.forename: K
authors.initials: K
authors.lastname: McMillan
authors.forename: E A
authors.initials: EA
authors.lastname: Sheta
authors.forename: J S
authors.initials: JS
authors.lastname: Nishimura
authors.forename: L J
authors.initials: LJ
authors.lastname: Roman
authors.forename: P
authors.initials: P
authors.lastname: Martasek
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D005609:Free Radicals; D006420:Hemeproteins / Q000737:chemistry; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000737:chemistry* / Q000378:metabolism; D009474:Neurons / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005609:Free Radicals; D006420:Hemeproteins; D007527:Isoenzymes; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D003545:Cysteine