1.14.13.39 (6R,S)-Methyl-tetrahydropterin activation in the absence of biopterin, not as effective as tetrahydrobiopterin 440195 1.14.13.39 2',3'-bis-O-(carboxymethyl)-5'-deoxy-5'-(4-([methyl(4-[(1E,3E)-4-[4-(methylamino)phenyl]buta-1,3-dien-1-yl]phenyl)amino]methyl)-1H-1,2,3-triazol-1-yl)adenosine nanotrigger NT2-2 764203 1.14.13.39 2'-O-(carboxymethyl)-5'-deoxy-5'-(4-([methyl(4-[(1E,3E)-4-[4-(methylamino)phenyl]buta-1,3-dien-1-yl]phenyl)amino]methyl)-1H-1,2,3-triazol-1-yl)adenosine nanotrigger NT2-6 764203 1.14.13.39 3'-O-(carboxymethyl)-5'-deoxy-5'-(4-([methyl(4-[(1E,3E)-4-[4-(methylamino)phenyl]buta-1,3-dien-1-yl]phenyl)amino]methyl)-1H-1,2,3-triazol-1-yl)adenosine nanotrigger NT2-4 764203 1.14.13.39 5'-(4-([(4-[(1E,3E)-4-(4-aminophenyl)buta-1,3-dien-1-yl]phenyl)(methyl)amino]methyl)-1H-1,2,3-triazol-1-yl)-2',3'-bis-O-(carboxymethyl)-5'-deoxyadenosine nanotrigger NT2-3 764203 1.14.13.39 5'-(4-([(4-[(1E,3E)-4-(4-aminophenyl)buta-1,3-dien-1-yl]phenyl)(methyl)amino]methyl)-1H-1,2,3-triazol-1-yl)-2'-O-(carboxymethyl)-5'-deoxyadenosine nanotrigger NT2-7 764203 1.14.13.39 5'-(4-([(4-[(1E,3E)-4-(4-aminophenyl)buta-1,3-dien-1-yl]phenyl)(methyl)amino]methyl)-1H-1,2,3-triazol-1-yl)-3'-O-(carboxymethyl)-5'-deoxyadenosine nanotrigger NT2-5 764203 1.14.13.39 5'-(4-([(4-[(1E,3E)-4-(4-aminophenyl)buta-1,3-dien-1-yl]phenyl)(methyl)amino]methyl)-1H-1,2,3-triazol-1-yl)-5'-deoxyadenosine nanotrigger NT2-9 764203 1.14.13.39 5'-[2-[ethyl[4-[4-(4-aminophenyl)-1,3-butadienyl]phenyl]amino]ethylamino]-5'-oxo-5'-deoxyadenosine 2'-phosphoric acid nanotrigger NT1 764203 1.14.13.39 A-23187 low levels of A-23187 stimulate nNOS activity 699996 1.14.13.39 Acetylsalicylic acid maximal activation at 0.004 mM 684277 1.14.13.39 Ca2+/calmodulin activate the electron transfer 673804 1.14.13.39 Ca2+/calmodulin calmodulin activates electron transfer from NADPH through three reductase domains to the oxygenase domain, controls constitutive isoforms through regulation of electron transfer between NADPH and heme 674558 1.14.13.39 Ca2+/calmodulin calmodulin activates electron transfer from NADPH through three reductase domains to the oxygenase domain, controls constitutive isoforms through regulation of electrontransfer between NADPH and heme 674558 1.14.13.39 Calmodulin - 659646, 660022, 764203, 765745 1.14.13.39 Calmodulin activates O2 consumption of eNOS 687615 1.14.13.39 Calmodulin activates the neuronal NOS by binding and inhibiting the suppression through the C-terminal tail of the enzyme, overview 685120 1.14.13.39 Calmodulin Ca2+-calmodulin binds between the reductase and oxygenase domains to activate nitric-oxide synthesis. The enzyme adopts an ensemble of open and closed conformational states and that Ca2+-calmodulin binding induces a dramatic rearrangement of the reductase domain. Calmodulin-specific activation triggers release and rotation of the FMN subdomain to expose the flavin for electron transfer to the heme 745299 1.14.13.39 Calmodulin in the neuronal enzyme, protein domain dynamics and calmodulin binding are implicated in regulating electron flow from NADPH, through the FAD and FMN cofactors, to the heme oxygenase domain, the site of NO generation. Binding of NADPH and calmodulin influence interdomain distance relationships as well as reaction chemistry. An important effect of calmodulin binding is to suppress adventitious electron transfer from nNOS to molecular oxygen and thereby preventing accumulation of reactive oxygen species 745293 1.14.13.39 Calmodulin required 658405, 658767, 763831 1.14.13.39 Calmodulin required for catalysis 687291 1.14.13.39 Calmodulin substrate 2,6-dichlorophenolindophenol, about 10fold increase in activity in presence of calmodulin 657741 1.14.13.39 dithiothreitol - 440234, 440235, 440236, 440238, 440240 1.14.13.39 dithiothreitol requirement 440207 1.14.13.39 heat shock protein 90 heat shock protein 90 enhances the affinity of wild-type enzyme to NADPH, L-arginine, and calmodulin but not to Ca2+ and BH4 746226 1.14.13.39 interferon gamma activates 440201, 440238 1.14.13.39 L-arginine L-arginine strongly stimulates oxygen consumption of eNOS and inhibits that of nNOS, nonhydrolyzable L-arginine analogues are not stimulatory 687615 1.14.13.39 lipopolysaccharide from Escherichia coli, activates 440238 1.14.13.39 additional information design and synthesis of a series of two-photon absorbing and photoactivatable NADPH analogues (NT 1 and NT2). These compounds bear one or two carboxymethyl group(s) on the 2'- or/and 3'-position(s) of the ribose in the adenosine moiety, instead of a 2'-phosphate group, and differ by the nature of the electron donor in their photoactivatable chromophore (replacing the nicotinamide moiety). Ability of NTs to photoinduce eNOS-dependent NO production in endothelial cells. Two compounds, those bearing a single carboxymethyl group on the 3'-position of the ribose, colocalize with the Golgi apparatus (the main intracellular location of eNOS) and display high intracellular two-photon brightness. Furthermore, a eNOS-dependent photooxidation is observed for these two compounds only, which is accompanied by a substantial intracellular NO production accounting for specific photocytotoxic effects. NT photoactivation efficiently triggers electron flow at the eNOS level and increases the basal production of NO by endothelial cells, structure-activity relationship of NTs in the cell context, overview 764203 1.14.13.39 additional information fibroblast growth factor-2 teratment up-regulates the enzyme in tectume, but down-regultes it in the optic nerve, overview 672844 1.14.13.39 additional information hepatic isozyme iNOS expression is induced in chronic liver cirrhosis early stages 677252 1.14.13.39 additional information iNOS is induced by pathogens and their components, e.g. induction in alveolar macropages by infection with the intracellular pathogen Mycobacterium bovis 690183 1.14.13.39 additional information neopterin derivatives are completely inactive and do not bind to the enzyme 440194, 440215 1.14.13.39 additional information short-term (20-30 min) treatment of endothelial cells with the synthetic NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-aminoethyl)amino](diazen-1-ium-1,2-diolate) increases the Ser1177 phosphorylation of the constitutively expressed endothelial NOS and the production of endogenous NO generated by eNOS from L-arginine, the phosphorylation of eNOS is Akt-dependent and completely reverted by the phosphatidylinositol-3 kinase inhibitor LY-294002 697713 1.14.13.39 tetrahydrobiopterin - 660022, 687572 1.14.13.39 thyroxin 0.001 mg thyroxin significantly increases nNOS activity and nNOS protein level to 153% compared to control 700433