Literature summary for 1.14.13.39 extracted from

Chennoufi, R.; Cabrie, A.; Nguyen, N.H.; Bogliotti, N.; Simon, F.; Cinquin, B.; Tauc, P.; Boucher, J.L.; Slama-Schwok, A.; Xie, J.; Deprez, E.
Light-induced formation of NO in endothelial cells by photoactivatable NADPH analogues targeting nitric-oxide synthase (2019), Biochim. Biophys. Acta, 1863, 1127-1137 .

Search for more literature for 1.14.13.39

Activating Compound

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

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

Localization	Comment	Organism	GeneOntology No.	Textmining
Golgi apparatus	-	Homo sapiens	5794	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	required	Homo sapiens
Fe2+	in the heme	Homo sapiens

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Homo sapiens	P29474	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
endothelial cell	human umbilical vein endothelial cells	Homo sapiens	-
HUVEC cell	-	Homo sapiens	-

Substrates and Products (Substrate)

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

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 [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
FAD	-	Homo sapiens
heme	-	Homo sapiens
NADPH	-	Homo sapiens

General Information

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

Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.

Release 2023.1 (January 2023)