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Information on EC 1.14.13.39 - nitric-oxide synthase (NADPH) and Organism(s) Homo sapiens and UniProt Accession P29474

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IUBMB Comments
The enzyme consists of linked oxygenase and reductase domains. The eukaryotic enzyme binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin, and its two domains are linked via a regulatory calmodulin-binding domain. Upon calcium-induced calmodulin binding, the reductase and oxygenase domains form a complex, allowing electrons to flow from NADPH via FAD and FMN to the active center. The reductase domain of the enzyme from the bacterium Sorangium cellulosum utilizes a [2Fe-2S] cluster to transfer the electrons from NADPH to the active center. cf. EC 1.14.14.47, nitric-oxide synthase (flavodoxin).
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Homo sapiens
UNIPROT: P29474
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
hide(Overall reactions are displayed. Show all >>)
Synonyms
nos, inducible nitric oxide synthase, endothelial nitric oxide synthase, inducible no synthase, neuronal nitric oxide synthase, inducible nos, endothelial no synthase, endothelial nos, neuronal nos, no-synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
endothelial nitric oxide synthase
-
endothelial nitric-oxide synthase
-
endothelial NOS
nitric oxide synthase
-
nitric-oxide synthase
-
NO synthase type III
eNOS
cb-NOS
-
isoform I, constitutive, from brain
cytokine inducible NOS
-
-
e-NOS
-
endothelial isoform III
EC-NOS
-
isoform III, in endothelial cells
endothelial nitric oxide synthase
-
-
endothelial nitric-oxide synthase
-
-
endothelial NO synthase
-
-
endothelial NOS
-
-
endothelium-derived relaxation factor-forming enzyme
-
-
-
-
endothelium-derived relaxing factor synthase
-
-
-
-
i-NOS
-
isoform II, inducible
inducible nitric oxide synthase
inducible NO synthase
-
inducible NOS
-
isoform
mitochondrial NO synthase
-
-
mtNOS
-
-
n-NOS
-
isoform I, neuronal enzyme
NADPH-diaphorase
-
-
-
-
neuronal nitric oxide synthase
neuronal NO synthase
neuronal NOS
nitric oxide synthase
nitric oxide synthetase
-
-
-
-
NO synthase
-
-
-
-
NO synthase type I
nNOS
NO synthase type II
iNOS
NO-synthase
-
-
NOS1
-
-
synthetase, nitric oxide
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
interaction and electrontransfer between enzyme domains and bound cofactors calmodulin, FMN, FAD, tetrahydrobiopterin, heme, and NADPH, overview
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)
The enzyme consists of linked oxygenase and reductase domains. The eukaryotic enzyme binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin, and its two domains are linked via a regulatory calmodulin-binding domain. Upon calcium-induced calmodulin binding, the reductase and oxygenase domains form a complex, allowing electrons to flow from NADPH via FAD and FMN to the active center. The reductase domain of the enzyme from the bacterium Sorangium cellulosum utilizes a [2Fe-2S] cluster to transfer the electrons from NADPH to the active center. cf. EC 1.14.14.47, nitric-oxide synthase (flavodoxin).
CAS REGISTRY NUMBER
COMMENTARY hide
125978-95-2
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
show the reaction diagram
-
-
-
?
1,4-bis-[[2-(dimethylamino-N-oxide)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + NADPH
1-[[2-(dimethylamino-N-oxide)ethyl]amino]-4-[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + ?
show the reaction diagram
-
-
-
ir
1-[[2-(dimethylamino-N-oxide)ethyl]amino]-4-[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + NADPH
1,4-bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + ?
show the reaction diagram
-
-
-
ir
2 L-arginine + 2 NADPH + 2 H+ + 2 O2
2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
show the reaction diagram
-
first half reaction
-
-
ir
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
show the reaction diagram
adriamycin + NADPH + O2
? + NO + NADP+
show the reaction diagram
-
-
-
-
?
menadione + NADPH + O2
? + NO + NADP+
show the reaction diagram
-
-
-
-
?
mitomycin c + NADPH + O2
? + NO + NADP+
show the reaction diagram
-
-
-
-
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
L-citrulline + NADP+ + NO + H2O
show the reaction diagram
-
second half reaction
-
-
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
show the reaction diagram
-
-
-
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
show the reaction diagram
-
NO from acetylsalicylic acid-activated enzyme is involved in thrombolysis, overview
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(6R)-5,6,7,8-tetrahydro-L-biopterin
-
NADPH
(6R)-5,6,7,8-tetrahydro-L-biopterin
-
5,6,7,8-tetrahydro-L-biopterin
Calmodulin
NADPH
tetrahydrobiopterin
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
Iron
heme iron, FMN/heme electron transfer
Ca2+/calmodulin
-
activate the electron transfer
Fe2+
-
-
O2
-
oxygen tension influences the activity
Zinc
-
0.43 mol per mol of subunit
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N''-nitroguanidine
-
3-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-ylamino]propan-1-ol
-
4-oxononenal
ONE, a highly bioreactive agent, able to inhibit eNOS activity and NO production. It can posttranslationally modify the enzyme in the placenta
-
L-N-methylarginine
NOS inhibitor, complete inhibition at 0.5 mM
L-Nomega-nitroarginine-(4R)-amino-L-proline amide
-
L-Nomega-nitroarginine-2,4-L-diaminobutyramide
-
L-omega-monomethyl L-arginine
potent competitive eNOS inhibitor, complete inhibition at 10 mM
N1-[cis-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(4'-chlorobenzyl)ethane-1,2-diamine
-
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
-
N1-[trans-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(3'-chlorobenzyl)ethane-1,2-diamine
-
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
-
Nomega-nitro-L-arginine methylester
L-NAME, the NOS inhibitor targets the oxygenase domain of the enzyme
-
(4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N''-nitroguanidine
-
3-bromo-7-nitroindazole
nNOS-specific inhibitor, complete inhibition at 0.01 mM
3-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-ylamino]propan-1-ol
-
4-(3-amino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.0076 mM
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.004 mM
4-(3-dimethylamino-propoxy)-1H-quinolin-2-one
-
IC50: 0.0026 mM
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
-
IC50: 90 nM, pharmacokinetic profile
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.0041 mM
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
-
IC50: 0.00011mM
7-nitroindazole
-
-
agmatine
AR-R17477
-
-
Calmidazolium
-
-
cyanide
-
heme-blocker inhibits superoxide formation after pretreatment of the enzyme
H2O2
-
alters heme group, decrease in activity
imidazole
-
heme-blocker inhibits superoxide formation after pretreatment of the enzyme
inhibitor NS1
-
is a new prototype of a reversible inhibitor of constitutive NOS targeting their reductase domain. NS1 is designed by molecular modelling, by replacing the imbedded NADP cofactor in neuronal NOS reductase domain. NS1 shares with NADPH the nucleotide moiety that allows proper targeting to the NADPH site. NS1 competes with NADPH binding
L-N-methylarginine
NOS inhibitor, complete inhibition at 0.5 mM
L-Nomega-nitroarginine-(4R)-amino-L-proline amide
-
L-Nomega-nitroarginine-2,4-L-diaminobutyramide
-
N(G),N(G)-dimethyl-L-arginine
-
asymmetric dimethyl arginine
N-nitro-L-arginine methyl ester
-
competitive NOS inhibitor
N1-[cis-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(4'-chlorobenzyl)ethane-1,2-diamine
-
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
-
N1-[trans-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(3'-chlorobenzyl)ethane-1,2-diamine
-
Ngamma-monomethyl-L-arginine
Ngamma-nitro-L-arginine
Ngamma-nitro-L-arginine methyl ester
-
only L-isomer, inhibits NO and citrulline production from L-arginine as well as superoxide formation in absence of tetrahydropterin
NXN-188
-
a dual-action oral therapeutic being developed for the treatment of acute migraine. The pharmacological mechanism of action of NXN-188 involves inhibition of both the neuronal nitric oxide synthase enzyme isoform and affinity for serotonin receptors. Clinical studies and pharmacokinetics, detailed overview
thiocoumarin
-
IC50: 0.018 mM
Trifluoperazine
-
inhibition in the presence of Ca2+, reversible by calmodulin
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
-
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
-
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
-
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
-
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
-
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
-
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
-
5'-[2-[ethyl[4-[4-(4-aminophenyl)-1,3-butadienyl]phenyl]amino]ethylamino]-5'-oxo-5'-deoxyadenosine 2'-phosphoric acid
nanotrigger NT1
-
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
-
Calmodulin
Acetylsalicylic acid
-
maximal activation at 0.004 mM
Ca2+/calmodulin
-
activate the electron transfer
-
Calmodulin
-
-
dithiothreitol
-
-
tetrahydrobiopterin
-
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.012 - 0.078
adriamycin
0.0019 - 0.022
L-arginine
0.01 - 0.041
menadione
0.0073 - 0.055
mitomycin C
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.8 - 95
adriamycin
6.6 - 96
menadione
0.62 - 26
mitomycin C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.08
(4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N''-nitroguanidine
wild type eNOS
0.3666
3-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-ylamino]propan-1-ol
wild type eNOS
0.11
L-Nomega-nitroarginine-(4R)-amino-L-proline amide
wild type eNOS
0.107
L-Nomega-nitroarginine-2,4-L-diaminobutyramide
wild type eNOS
0.0852
N1-[cis-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(4'-chlorobenzyl)ethane-1,2-diamine
wild type eNOS
0.4167
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
wild type eNOS
0.0952
N1-[trans-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(3'-chlorobenzyl)ethane-1,2-diamine
wild type eNOS
0.00015
(4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N''-nitroguanidine
wild type nNOS
0.0094 - 0.0492
3-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-ylamino]propan-1-ol
0.66
agmatine
-
at lower concentration than the Ki value agmatine leads to time-, concentration-, NADPH- and calmodulin-dependent inhibition of the neuronal enzyme in presence of calmodulin
0.0001
L-Nomega-nitroarginine-(4R)-amino-L-proline amide
wild type nNOS
0.0003
L-Nomega-nitroarginine-2,4-L-diaminobutyramide
wild type nNOS
0.000085 - 0.0012
N1-[cis-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(4'-chlorobenzyl)ethane-1,2-diamine
0.000388 - 0.0367
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
0.00025 - 0.0061
N1-[trans-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(3'-chlorobenzyl)ethane-1,2-diamine
0.0007
Ngamma-monomethyl-L-arginine
-
endothelial isoform
0.00002
Ngamma-nitro-L-arginine
-
irreversible inactivation of endothelial isoform after preincubation
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0076
4-(3-amino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Homo sapiens
-
IC50: 0.0076 mM
0.004
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Homo sapiens
-
IC50: 0.004 mM
0.0026
4-(3-dimethylamino-propoxy)-1H-quinolin-2-one
Homo sapiens
-
IC50: 0.0026 mM
0.00009
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Homo sapiens
-
IC50: 90 nM, pharmacokinetic profile
0.0041
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Homo sapiens
-
IC50: 0.0041 mM
0.00011
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Homo sapiens
-
IC50: 0.00011mM
0.018
thiocoumarin
Homo sapiens
-
IC50: 0.018 mM
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.074
-
purified enzyme
0.142
-
wild-type
0.159
-
mutant E298D
0.181
-
partially purified enzyme
0.19
-
purified recombinant enzyme
0.34 - 0.35
-
purified enzyme, recombinant, determined as NADPH-oxidase activity
1
-
purified enzyme
38
-
purified enzyme, inducible isoform, cytochrome c reductase activity
additional information
-
assay method
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
assay at
7.6
assay at
7
-
assay at
7.4
-
assay at
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
-
about, assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
human umbilical vein endothelial cells
Manually annotated by BRENDA team
-
isoform I
Manually annotated by BRENDA team
-
isozyme NOS3
Manually annotated by BRENDA team
-
cell line ME-180, constitutive expression
Manually annotated by BRENDA team
-
two populations of NADPH diaphorase-positive neurons exist in the human claustrustrum. One is comprised of large and medium cells consistent with a projection neuron phenotype, the other is represented by small cells resembling the interneuron phenotype as defined by previous Golgi impregnation studies. NADPH diaphorase-reactive neurons are heterogenously distributed throughout the claustrum
Manually annotated by BRENDA team
-
cell line A-172, american type
Manually annotated by BRENDA team
-
isoform II
Manually annotated by BRENDA team
-
macula densa cells, isoform I
Manually annotated by BRENDA team
-
constitutive expression of full length nitric oxide synthase isoforms. Lymphocytes express more inducible nitric oxide synthase transcripts and protein than neuronal nitric oxide synthase and endothelial nitric oxide synthase
Manually annotated by BRENDA team
-
isozyme NOS1
Manually annotated by BRENDA team
-
constitutive expression of full length nitric oxide synthase isoforms. Isolated monocytes express more endothelial nitric oxide synthase transcript and protein as compared to neuronal nitric oxide synthase and inducible nitric oxide synthase
Manually annotated by BRENDA team
-
isozyme NOS1
Manually annotated by BRENDA team
-
islet cells, isoform I
Manually annotated by BRENDA team
-
constitutive expression of full length nitric oxide synthase isoforms with the highest expression of inducible nitric oxide synthase in comparison to neuronal nitric oxide synthase and endothelial nitric oxide synthase
Manually annotated by BRENDA team
-
isozyme NOS3
Manually annotated by BRENDA team
-
isoform I
Manually annotated by BRENDA team
-
red pulp, eosinophils and neutrophils, isoform II
Manually annotated by BRENDA team
-
i.e. HUVEC cells
Manually annotated by BRENDA team
additional information
-
3 isoforms: 1. neuronal, soluble isoform I is constitutively expressed in brain and other tissues and Ca2+-regulated, 2. soluble isoform II is usually not constitutively expressed, but inducible in macrophages and other cells, 3. isoform III is membrane-bound and expressed in endothelial cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
-
3 isoforms: 1. neuronal, soluble isoform I is constitutively expressed in brain and other tissues and Ca2+-regulated, 2. soluble isoform II is usually not constitutively expressed, but inducible in macrophages and other cells, 3. isoform III is membrane-bound and expressed in endothelial cells
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia (PE), multifactorial pregnancy disease, characterized by new-onset gestational hypertension with (or without) proteinuria or end-organ failure, exclusively observed in humans. PE pathophysiology can result from abnormal placentation due to a defective trophoblastic invasion and an impaired remodeling of uterine spiral arteries, leading to a poor adaptation of utero-placental circulation. This would be associated with hypoxia/ reoxygenation phenomena, oxygen gradient fluctuations, altered antioxidant capacity, oxidative stress, and reduced nitric oxide (NO) bioavailability. This results in part from the reaction of NO with the radical anion superoxide, which produces peroxynitrite ONOO-, a powerful pro-oxidant and inflammatory agent. Another mechanism is the progressive inhibition of the placental endothelial nitric oxide synthase (eNOS) by oxidative stress, which results in eNOS uncoupling via several events such as a depletion of the eNOS substrate L-arginine due to increased arginase activity, an oxidation of the eNOS cofactor tetrahydrobiopterin (BH4), or eNOS posttranslational modifications (for instance by S-glutathionylation). The uncoupling of eNOS triggers a switch of its activity from a NO-producing enzyme to a NADPH oxidase-like system generating superoxide, thereby potentiating ROS production and oxidative stress. Moreover, in PE placentas, eNOS can be posttranslationally modified by lipid peroxidation-derived aldehydes such as 4-oxononenal (ONE) a highly bioreactive agent, able to inhibit eNOS activity and NO production. Analysis of the dysfunction of placental eNOS evoked by oxidative stress and lipid peroxidation products, and the potential consequences on PE pathogenesis, detailed overview. Oxidative stress is thought to play a pivotal role in the decreased NO bioavailability in PE pathophysiology, via several mechanisms including an inhibition of eNOS (eNOS uncoupling) and subsequent defect of NO biosynthesis, or through the formation of peroxynitrite, via the reaction of NO with the radical anion superoxide. eNOS inhibition is associated with a decrease in endothelial-dependent relaxation in vitro and in vivo. Therapeutic perspectives targeting oxidative stress and NO/eNOS dysfunction
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
NOS3_HUMAN
1203
0
133275
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
135000
-
x * 135000, SDS-PAGE
15000
x * 15000, SDS-PAGE
150000
SDS-PAGE
160000
19000
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
dimer
monomer
additional information
-
gel filtration: native protein is a dimer, especially in presence of tetrahydrobiopterin and L-arginine, but dissociates at low temperature to monomers during gel electrophoresis
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
lipoprotein
in PE placentas, eNOS can be posttranslationally modified by lipid peroxidation-derived aldehydes such as malondialdehyde or as 4-oxononenal (ONE) a highly bioreactive agent, able to inhibit eNOS activity and NO production. They covalently bind to the nucleophilic sulfhydryl and primary amine groups of proteins, forming Schiff bases, Michael adducts and protein crosslinks. The modification of proteins by lipid peroxidation products (LPPs) depends on their nature, expression and conformation, oxidative stress intensity and duration, cell type, local LPP concentration, and generates various biological responses from the expression of protective and adaptive factors to protein dysfunction, inflammation, senescence and apoptosis. The presence of LPPs in PE placentas, could be indicative of their premature senescence, in agreement with the hypothesis that accelerated placental aging is involved in PE pathophysiology via oxidative stress
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method
in complex with inhibitor AR
-
sitting drop vapor diffusion method
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G2A
the mutant is defective in activity and cellular localization
C563R
interdomain electron transfer rate is similar to that of the wildtype
D597N/M336V
mutant of nNOS, the Ki values for the nNOS double mutant increase for all inhibitors but the mutant still binds these inhibitors better than eNOS
E298D
-
comparable to wild-type in heme and flavin content, in affinity to calmodulin and dimerization
R536E
mutant constructed to disrupt the bridging calmodulin/nitric oxide synthase interaction. The FMN-heme interdomain electron transfer rate is decreased by 96%
S562K
inducible nitric oxide synthase mutant in an oxygenase/FMN construct. The interdomain electron transfer rate constant of the mutant is decreased by one third, and its flavin fluorescence intensity per micromole per liter is diminished by approximately 24% suggesting that a positive charge at position 562 destabilizes the hydrogen-bond-mediated nitric oxide synthase/calmodulin alignment, resulting in slower FMN-heme interdomain electron transfer
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
inducible isoform is unstable during purification in absence of L-arginine and tetrahydrobiopterin toward loss of the heme group and formation of low-spin species
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni Sepharose column chromatography, 2',5'-ADP Sepharose column chromatography, and Superdex 200 gel filtration
affinity and size exclusion chromatography
-
native enzyme from platelets activated by acetylsalicylic acid, by solubilization with Triton X-100, anion exchange chromatography, and gel filtration, to homogeneity
-
Ni Sepharose column chromatography, 2',5'-ADP Sepharose column chromatography, and Superdex 200 gel filtration
partial, 2',5'-ADP-agarose affinity chromatography
-
recombinant from Pichia pastoris
-
recombinant wild-type of inducible liver isoform from Escherichia coli with and without His-tag, requires inclusion of tetrahydrobiopterin in purification buffer
-
wild-type recombinant from insect cells
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
cell-specific gene regulation mechanism of the endothelial isozyme in the vascular endothelium involving endothelial-specific promoter, binding sites for AP-1, high affinity Sp1-binding sites and GATA promoter sites, and several, e.g. octameric, transcriptional regulators, epigenetic regulatory mechanisms in vascular endothelial cell-specific gene expression, overview, the cell-specific chromatin structure regulates transcription, and transcription factors, e.g. Sp1, AP-1, GATA-2, and octamer KLF, regulate transcription via chromatin-remodeling activity, overlapping cis antisense gene, endothelial-specific genetic regulation model, overview
-
co-expression of the enzyme and Vac14 as GST- or His-tagged proteins in Escherichia colis train BL21, expression of Vac14 as FLAG-tagged protein in HEK-293T cells
-
endothelial enzyme expressed in Pichia pastoris using a highly inducible alcohol oxidase promoter PAOX1
-
expressed in Escherichia coli BL21(DE3) cells
expressed in SH-SY5Y cells
expression in HUVE cells, vascular smooth muscle cells, and in HeLa cells, DNA methylation of proximal promoter sequences of eNOS promoter-beta-Gal fusion contructs in trangenic mice is not essential for cell-specific expression, endothelial cells are highly enriched in acetylated H3 and acetylated H4 at the eNOS promoter altering the promoter function and expression
-
inducible liver isoform is expressed in Escherichia coli with and without His-tag, requires coexpression of calmodulin
-
neuronal enzyme expressed in Spodoptera frugiperda cells via baculovirus infection
-
wild-type endothelial enzyme is expressed in insect cells via baculovirus infection
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression of eNOS mRNA and protein does not change in mild to moderate chronic obstructive pulmonary disease, but is reduced in the more severe stages of chronic obstructive pulmonary disease
in the peripheral lung of chronic obstructive pulmonary disease patients iNOS mRNA expression is increased at earlier stages of the disease but decreases in the most severe patients, pro-inflammatory cytokine-induced iNOS expression is decreased by oxidative stress, such as H2O2, cigarette smoke conditioned media, and the peroxyntrite generator SIN1
lung tissue from patients with severe and very severe chronic obstructive pulmonary disease have graded increases in nNOS (mRNA and protein) compared with non-smokers and normal smokers
neither interleukin-1 nor tissue necrosis factor-alpha is capable of inducing nNOS synthesis for up to 48 h treatment, treatment with insulin-like growth factor-1 or transforming growth factor-beta for up to 48 h has no effect on the levels of nNOS
treatment with insulin-like growth factor-1 or transforming growth factor-beta for up to 48 h has no effect on the levels of iNOS
treatment with interleukin-1 or tissue necrosis factor-alpha for 16 h significantly increases iNOS levels to 429.4% of the control
up-regulation of the inflammatory gene encoding for iNOS is observed in a population of amoeboid microglial cells from Parkinson's disease patients, iNOS up-regulation in microglia seems to play an important role in the onset of inflammatory processes in Parkinsons's disease and acts synergistically with other inflammatory mediators, Parkinsons's disease-inducing drugs such as rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or dopamine overexposure provoke activation of iNOS expression
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
no evidence for altered enzyme function of mutant E298D that could explain endothelial dysfunction associated with the E298D polymorphism
pharmacology
-
NO synthase can be used to gain insight into the biological role of endogenous agmatine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Klatt, P.; Heinzel, B.; Mayer, B.; Ambach, E.; Werner-Felmayer, G.; Wachter, H.; Werner, E.R.
Stimulation of human nitric oxide synthase by tetrahydrobiopterin and selective binding of the cofactor
FEBS Lett.
305
160-162
1992
Homo sapiens
Manually annotated by BRENDA team
Schmidt, H.H.H.W.; Murad, F.
Purification and characterization of a human NO synthase
Biochem. Biophys. Res. Commun.
181
1372-1377
1991
Homo sapiens
Manually annotated by BRENDA team
Werner-Felmayer, G.; Werner, E.R.; Fuchs, D.; Hausen, A.; Mayer, B.; Reibnegger, G.; Weiss, G.; Wachter, H.
Calcium/calmodulin-dependent nitric oxide synthase activity in the human cervix carcinoma cell line ME-180
Biochem. J.
289
357-361
1993
Homo sapiens
-
Manually annotated by BRENDA team
Leber, A.; Hemmens, B.; Klosch, B.; Goessler, W.; Raber, G.; Mayer, B.; Schmidt, K.
Characterization of recombinant human endothelial nitric-oxide synthase purified from the yeast Pichia pastoris
J. Biol. Chem.
274
37658-37664
1999
Homo sapiens
Manually annotated by BRENDA team
Xia, Y.; Tsai, A.L.; Berka, V.; Zweier, J.L.
Superoxide generation from endothelial nitric-oxide synthase. A Ca2+/calmodulin-dependent and tetrahydrobiopterin regulatory process
J. Biol. Chem.
273
25804-25808
1998
Homo sapiens
Manually annotated by BRENDA team
McMillan, K.; Adler, M.; Auld, D.S.; Baldwin, J.J.; Blasko, E.; Browne, L.J.; Chelsky, D.; Davey, D.; Dolle, R.E.; Eagen, K.A.; Erickson, S.; Feldman, R.I.; Glaser, C.B.; Mallari, C.; Morrissey, M.M.; Ohlmeyer, M.H.J.; Pan, G.; Parkinson, J.F.; Phillips, G.B.; Polokoff, M.A.; Sigal, N.H.; Vergona, R.; Whitlow, M.; Young, T.A.; Devlin, J.J
Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry
Proc. Natl. Acad. Sci. USA
97
1506-1511
2000
Homo sapiens, Mus musculus (P29477), Mus musculus
Manually annotated by BRENDA team
Foerstermann, U.; Closs, E.I.; Pollock, J.S.; Nakane, M.; Schwarz, P.; Gath, I.; Kleinert, H.
Nitric oxide synthase isoenzymes. Characterization, purification, molecular cloning, and functions
Hypertension
23
1121-1131
1994
Bos taurus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Demady, D.R.; Jianmongkol, S.; Vuletich, J.L.; Bender, A.T.; Osawa, Y.
Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme
Mol. Pharmacol.
59
24-29
2001
Homo sapiens
Manually annotated by BRENDA team
Reif, D.W.; McCreedy, S.A.
N-Nitro-L-arginine and N-monomethyl-L-arginine exhibit a different pattern of inactivation toward the three nitric oxide synthases
Arch. Biochem. Biophys.
320
170-176
1995
Homo sapiens, Mus musculus, Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Manually annotated by BRENDA team
Gerber, N.C.; Nishida, C.R.; de Montellano, P.R.O.
Characterization of human liver inducible nitric oxide synthase expressed in Escherichia coli
Arch. Biochem. Biophys.
343
249-253
1997
Homo sapiens
Manually annotated by BRENDA team
Fu, J.; Yamamoto, K.; Guan, Z.W.; Kimura, S.; Iyanagi, T.
Human neuronal nitric oxide synthase can catalyze one-electron reduction of adriamycin: role of flavin domain
Arch. Biochem. Biophys.
427
180-187
2004
Homo sapiens
Manually annotated by BRENDA team
Golser, R.; Gorren, A.C.; Mayer, B.; Schmidt, K.
Functional characterization of Glu298Asp mutant human endothelial nitric oxide synthase purified from a yeast expression system
Nitric Oxide
8
7-14
2003
Homo sapiens
Manually annotated by BRENDA team
Fedorov, R.; Vasan, R.; Ghosh, D.K.; Schlichting, I.
Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design
Proc. Natl. Acad. Sci. USA
101
5892-5897
2004
Homo sapiens, Rattus norvegicus (P29476), Mus musculus (P29477), Mus musculus
Manually annotated by BRENDA team
Enkhbaatar, P.; Murakami, K.; Shimoda, K.; Mizutani, A.; McGuire, R.; Schmalstieg, F.; Cox, R.; Hawkins, H.; Jodoin, J.; Lee, S.; Traber, L.; Herndon, D.; Traber, D.
Inhibition of neuronal nitric oxide synthase by 7-nitroindazole attenuates acute lung injury in an ovine model
Am. J. Physiol.
285
R366-372
2003
Homo sapiens
Manually annotated by BRENDA team
Dowling, R.B.; Newton, R.; Robichaud, A.; Cole, P.J.; Barnes, P.J.; Wilson, R.
Effect of inhibition of nitric oxide synthase on Pseudomonas aeruginosa infection of respiratory mucosa in vitro
Am. J. Respir. Cell Mol. Biol.
19
950-958
1998
Homo sapiens
Manually annotated by BRENDA team
Marchal, S.; Gorren, A.C.; Andersson, K.K.; Lange, R.
Hunting oxygen complexes of nitric oxide synthase at low temperature and high pressure
Biochem. Biophys. Res. Commun.
338
529-535
2005
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Jackson, S.A.; Sahni, S.; Lee, L.; Luo, Y.; Nieduzak, T.R.; Liang, G.; Chiang, Y.; Collar, N.; Fink, D.; He, W.; Laoui, A.; Merrill, J.; Boffey, R.; Crackett, P.; Rees, B.; Wong, M.; Guilloteau, J.P.; Mathieu, M.; Rebello, S.S.
Design, synthesis and characterization of a novel class of coumarin-based inhibitors of inducible nitric oxide synthase
Bioorg. Med. Chem.
13
2723-2739
2005
Homo sapiens, Rattus norvegicus, Mus musculus (P29477), Mus musculus
Manually annotated by BRENDA team
Fish, J.E.; Marsden, P.A.
Endothelial nitric oxide synthase: insight into cell-specific gene regulation in the vascular endothelium
Cell. Mol. Life Sci.
63
144-162
2006
Homo sapiens
Manually annotated by BRENDA team
Lemaire, J.F.; McPherson, P.S.
Binding of Vac14 to neuronal nitric oxide synthase: characterisation of a new internal PDZ-recognition motif
FEBS Lett.
580
6948-6954
2006
Homo sapiens
Manually annotated by BRENDA team
Chen, K.; Popel, A.S.
Vascular and perivascular nitric oxide release and transport: Biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)
Free Radic. Biol. Med.
42
811-822
2007
Homo sapiens
Manually annotated by BRENDA team
Fish, J.E.; Matouk, C.C.; Rachlis, A.; Lin, S.; Tai, S.C.; DAbreo, C.; Marsden, P.A.
The expression of endothelial nitric-oxide synthase is controlled by a cell-specific histone code
J. Biol. Chem.
280
24824-24838
2005
Homo sapiens
Manually annotated by BRENDA team
Ghosh, D.K.; Holliday, M.A.; Thomas, C.; Weinberg, J.B.; Smith, S.M.; Salerno, J.C.
Nitric-oxide synthase output state. Design and properties of nitric-oxide synthase oxygenase/FMN domain constructs
J. Biol. Chem.
281
14173-14183
2006
Mus musculus, Homo sapiens (P29474), Rattus norvegicus (P29476)
Manually annotated by BRENDA team
Karmohapatra, S.K.; Chakraborty, K.; Kahn, N.N.; Sinha, A.K.
The role of nitric oxide in aspirin induced thrombolysis in vitro and the purification of aspirin activated nitric oxide synthase from human blood platelets
Am. J. Hematol.
82
986-995
2007
Homo sapiens
Manually annotated by BRENDA team
Brindicci, C.; Kharitonov, S.A.; Ito, M.; Elliott, M.W.; Hogg, J.C.; Barnes, P.J.; Ito, K.
Nitric oxide synthase isoenzyme expression and activity in peripheral lungs of COPD patients
Am. J. Respir. Crit. Care Med.
181
21-30
2009
Homo sapiens (P29474), Homo sapiens (P29475), Homo sapiens (P35228), Homo sapiens
Manually annotated by BRENDA team
Mikula, I.; Durocher, S.; Martasek, P.; Mutus, B.; Slama-Schwok, A.
Isoform-specific differences in the nitrite reductase activity of nitric oxide synthases under hypoxia
Biochem. J.
418
673-682
2009
Homo sapiens, Homo sapiens (P29474), Homo sapiens (P29475)
Manually annotated by BRENDA team
Lenasi, H.; Strucl, M.
The effect of nitric oxide synthase and cyclooxygenase inhibition on cutaneous microvascular reactivity
Eur. J. Appl. Physiol.
103
719-726
2008
Homo sapiens (P29474), Homo sapiens
Manually annotated by BRENDA team
Schmidt, A.; Bilgasem, S.; Lorkowski, S.; Vischer, P.; Voelker, W.; Breithardt, G.; Siegel, G.; Buddecke, E.
Exogenous nitric oxide regulates activity and synthesis of vascular endothelial nitric oxide synthase
Eur. J. Clin. Invest.
38
476-485
2008
Homo sapiens
Manually annotated by BRENDA team
de Visser, S.P.; Tan, L.S.
Is the bound substrate in nitric oxide synthase protonated or neutral and what is the active oxidant that performs substrate hydroxylation?
J. Am. Chem. Soc.
130
12961-12974
2008
Homo sapiens
Manually annotated by BRENDA team
Nishida, C.R.; Ortiz de Montellano, P.R.
Reductive heme-dependent activation of the n-oxide prodrug AQ4N by nitric oxide synthase
J. Med. Chem.
51
5118-5120
2008
Homo sapiens (P35228)
Manually annotated by BRENDA team
Igarashi, J.; Li, H.; Jamal, J.; Ji, H.; Fang, J.; Lawton, G.R.; Silverman, R.B.; Poulos, T.L.
Crystal structures of constitutive nitric oxide synthases in complex with de novo designed inhibitors
J. Med. Chem.
52
2060-2066
2009
Homo sapiens (P29474), Homo sapiens (P29475)
Manually annotated by BRENDA team
Aquilano, K.; Baldelli, S.; Rotilio, G.; Ciriolo, M.R.
Role of nitric oxide synthases in Parkinsons disease: a review on the antioxidant and anti-inflammatory activity of polyphenols
Neurochem. Res.
33
2416-2426
2008
Homo sapiens, Homo sapiens (P29475), Homo sapiens (P35228)
Manually annotated by BRENDA team
Rosa, S.C.; Judas, F.; Lopes, M.C.; Mendes, A.F.
Nitric oxide synthase isoforms and NF-kappaB activity in normal and osteoarthritic human chondrocytes: regulation by inducible nitric oxide
Nitric Oxide
19
276-283
2008
Homo sapiens (P29475), Homo sapiens (P35228), Homo sapiens
Manually annotated by BRENDA team
Ibiza, S.; Perez-Rodriguez, A.; Ortega, A.; Martinez-Ruiz, A.; Barreiro, O.; Garcia-Dominguez, C.A.; Victor, V.M.; Esplugues, J.V.; Rojas, J.M.; Sanchez-Madrid, F.; Serrador, J.M.
Endothelial nitric oxide synthase regulates N-Ras activation on the Golgi complex of antigen-stimulated T cells
Proc. Natl. Acad. Sci. USA
105
10507-10512
2008
Homo sapiens (P29474)
Manually annotated by BRENDA team
Vaughan, D.; Speed, J.; Medve, R.; Andrews, J.S.
Safety and pharmacokinetics of NXN-188 after single and multiple doses in five phase I, randomized, double-blind, parallel studies in healthy adult volunteers
Clin. Ther.
32
146-160
2010
Homo sapiens
Manually annotated by BRENDA team
Saluja, R.; Jyoti, A.; Chatterjee, M.; Habib, S.; Verma, A.; Mitra, K.; Barthwal, M.K.; Bajpai, V.K.; Dikshit, M.
Molecular and biochemical characterization of nitric oxide synthase isoforms and their intracellular distribution in human peripheral blood mononuclear cells
Biochim. Biophys. Acta
1813
1700-1707
2011
Homo sapiens
Manually annotated by BRENDA team
Li, W.; Chen, L.; Fan, W.; Feng, C.
Comparing the temperature dependence of FMN to heme electron transfer in full length and truncated inducible nitric oxide synthase proteins
FEBS Lett.
586
159-162
2012
Homo sapiens
Manually annotated by BRENDA team
Li, W.; Fan, W.; Chen, L.; Elmore, B.O.; Piazza, M.; Guillemette, J.G.; Feng, C.
Role of an isoform-specific serine residue in FMN-heme electron transfer in inducible nitric oxide synthase
J. Biol. Inorg. Chem.
17
675-685
2012
Homo sapiens (P35228), Homo sapiens
Manually annotated by BRENDA team
Hinova-Palova, D.; Edelstein, L.; Landzhov, B.; Minkov, M.; Malinova, L.; Hristov, S.; Denaro, F.; Alexandrov, A.; Kiriakova, T.; Brainova, I.; Paloff, A.; Ovtscharoff, W.
Topographical distribution and morphology of NADPH-diaphorase-stained neurons in the human claustrum
Front. Syst. Neurosci.
8
96
2014
Homo sapiens
-
Manually annotated by BRENDA team
Rouaud, F.; Romero-Perez, M.; Wang, H.; Lobnysheva, I.; Ramassamy, B.; Henry, E.; Tauc, P.; Giacchero, D.; Boucher, J.L.; Deprez, E.; Rocchi, S.; Slama-Schwok, A.
Regulation of NADPH-dependent nitric oxide and reactive oxygen species signalling in endothelial and melanoma cells by a photoactive NADPH analogue
Oncotarget
5
10650-10664
2014
Homo sapiens, Mus musculus (P70313)
Manually annotated by BRENDA team
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
Biochim. Biophys. Acta
1863
1127-1137
2019
Homo sapiens (P29474)
Manually annotated by BRENDA team
Guerby, P.; Tasta, O.; Swiader, A.; Pont, F.; Bujold, E.; Parant, O.; Vayssiere, C.; Salvayre, R.; Negre-Salvayre, A.
Role of oxidative stress in the dysfunction of the placental endothelial nitric oxide synthase in preeclampsia
Redox Biol.
40
101861
2021
Homo sapiens (P29474), Homo sapiens
Manually annotated by BRENDA team