Activating Compound | Comment | Organism | Structure |
---|---|---|---|
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 | Homo sapiens | |
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 | Homo sapiens | |
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 | Homo sapiens | |
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 | Homo sapiens | |
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 | Homo sapiens | |
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 | Homo sapiens | |
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 | Homo sapiens | |
5'-[2-[ethyl[4-[4-(4-aminophenyl)-1,3-butadienyl]phenyl]amino]ethylamino]-5'-oxo-5'-deoxyadenosine 2'-phosphoric acid | nanotrigger NT1 | Homo sapiens | |
Calmodulin | - |
Homo sapiens | |
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 | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
nanoshutter NS1 | mixture of (2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-2-([2-(ethyl(4-[(E)-2-(4-nitrophenyl)ethenyl]phenyl)amino)ethyl]carbamoyl)-4-hydroxyoxolan-3-yl dihydrogen phosphate and (2R,3R,4R,5S)-2-(6-amino-9H-purin-9-yl)-5-([2-(ethyl(4-[(E)-2-(4-nitrophenyl)ethenyl]phenyl)amino)ethyl]carbamoyl)-4-hydroxyoxolan-3-yl dihydrogen phosphate. The NOS inhibitor targets the reductase domain of the enzyme | Homo sapiens | |
Nomega-nitro-L-arginine methylester | L-NAME, the NOS inhibitor targets the oxygenase domain of the enzyme | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
Golgi apparatus | - |
Homo sapiens | 5794 | - |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Ca2+ | required | Homo sapiens | |
Fe2+ | in the heme | Homo sapiens |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 | Homo sapiens | overall reaction | 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P29474 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
endothelial cell | human umbilical vein endothelial cells | Homo sapiens | - |
HUVEC cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 | overall reaction | Homo sapiens | 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O | - |
? |
Synonyms | Comment | Organism |
---|---|---|
endothelial nitric-oxide synthase | - |
Homo sapiens |
eNOS | - |
Homo sapiens |
nitric-oxide synthase | - |
Homo sapiens |
NOS | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | - |
Homo sapiens | |
heme | - |
Homo sapiens | |
NADPH | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | nitric oxide (NO) is a key cellular signaling mediator involved in the overall regulation of physiological homeostasis and in numerous pathological processes related to cardiovascular, nervous and immune systems. NO is formed together with L-citruline by nitric-oxide synthases (NOS) that catalyze the oxidation of L-arginine using nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), tetrahydrobiopterin (BH4) and O2 as cofactors. The overall catalytic process is driven by reducing equivalents supplied by NADPH. NOS are composed of a reductase domain which binds NADPH and the two flavins and an oxygenase domain which binds the heme, L-arginine, BH4 and O2. These two domains are connected by the calmodulin-binding domain. The electron flow leading to the formation of NO is initiated by the binding of NADPH to the reductase domain and requires the binding of calmodulin for efficient FMN to heme electron transfer. NO is produced by three NOS isoforms, the two first are constitutive, neuronal (nNOS) and endothelial (eNOS) whereas the third one is inducible (iNOS). Efficient photoactivatable NADPH analogues targeting NOS can have important implications for generating apoptosis in tumor cells or modulating NO-dependent physiological processes | Homo sapiens |