Any feedback?
No. of entries
Information on EC 1.14.13.39 - nitric-oxide synthase (NADPH)
for references in articles please use BRENDA:EC1.14.13.39
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree 1 Oxidoreductases
1.14 Acting on paired donors, with incorporation or reduction of molecular oxygen
1.14.13 With NADH or NADPH as one donor, and incorporation of one atom of oxygen into the other donor
1.14.13.39 nitric-oxide synthase (NADPH)
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).
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 1.14.13.39
- artery
- necrosis
- lipopolysaccharide
-
l-name
- lps
- tnf
- cardiovascular
- cox-2
- nitrite
- cyclooxygenase-2
- vessel
- hypertension
- cardiac
-
lps-induced
- dismutase
- cerebral
-
vasodilation
- nerve
- aortic
- ischemia
- pulmonary
- prostaglandin
- myocardial
- cgmp
- ng-nitro-l-arginine
- factor-alpha
- coronary
- acetylcholine
- wistar
-
endothelium-dependent
- tnf-alpha
- peroxynitrite
-
contractile
-
neuroprotective
-
lps-stimulated
-
reperfusion
- nf-kappab
-
nitrotyrosine
- microglia
- interferon-gamma
- nitroprusside
- ifn-gamma
-
vasoconstriction
-
guanylate
-
vasorelaxation
- il-1beta
-
lipopolysaccharide-induced
-
erectile
- endothelin-1
-
guanylyl
- pharmacology
- medicine
Reaction Schemes
show2
+
3
+
3
+
4
=
2
+
2
+
3
+
4
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
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
bacterial nitric oxide synthase
bacterial nitric-oxide synthase
bNOS
bsNOS
cb-NOS
e-NOS
EC-NOS
endothelial nitric oxide synthase
endothelial nitric-oxide synthase
endothelial NOS
endothelium-derived relaxation factor-forming enzyme
-
-
-
-
endothelium-derived relaxing factor synthase
-
-
-
-
eNOS
i-NOS
inducible nitric oxide synthase
inducible nitric-oxide synthase
inducible NO synthase
inducible NOS
iNOS
mtNOS
n-NOS
NADPH diaphorase
NADPH-d
NADPH-diaphorase
NADPHd
neuronal nitric oxide synthase
neuronal nitric-oxide synthase
neuronal NO synthase
neuronal NOS
nicotinamide adenine dinucleotide phosphate-diaphorase
nitric oxide synthase
nitric oxide synthetase
-
-
-
-
nitric-oxide synthase
nNOS
nNOSalpha
NO synthase
NO-synthase
NOS
NOS1
NOS2
NOS3
synthetase, nitric oxide
-
-
-
-
NADPH-diaphorase
-
-
-
-
nitric oxide synthase
-
-
-
-
nNOS
-
NO synthase
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 L-arginine + 2 NADPH + 2 H+ + 2 O2 = 2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
(1a)
-
-
-
2 Nomega-hydroxy-L-arginine + NADPH + H+ + 2 O2 = 2 L-citrulline + 2 nitric oxide + NADP+ + 2 H2O
(1b)
-
-
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
alignment of heme-binding domain amino acid sequences of NOS
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
dimerization is required, activation of NO-synthesis by enabling electron transfer between the reductase and the oxygenase domains, isolated monomers are inactive
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
possible mechanism
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
possible mechanism
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
relation between structure, function and binding of prosthetic groups during dissociation, unfolding and renaturation
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
isoform I and II are regulated by Ca2+/calmodulin, isoform II is Ca2+-independent, but requires calmodulin, inducible by cytokines
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
isoform I and II are regulated by Ca2+/calmodulin, isoform II is Ca2+-independent, but requires calmodulin, inducible by cytokines
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
isoform I and II are regulated by Ca2+/calmodulin, isoform II is Ca2+-independent, but requires calmodulin, inducible by cytokines
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
isoform I and II are regulated by Ca2+/calmodulin, isoform II is Ca2+-independent, but requires calmodulin, inducible by cytokines
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
isoform I and II are regulated by Ca2+/calmodulin, isoform II is Ca2+-independent, but requires calmodulin, inducible by cytokines
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
cytochrome P-450 enzyme
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
cytochrome P-450 enzyme
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
structure-function study of macrophage enzyme
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
subunits align in head-to-head manner with oxygenase domains interacting to form a dimer and reductase domains existing as independent extensions
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
analysis of catalytic site by Fourier transform infrared spectroscopy, extent of modulation of vibrational modes upon photolysis of CO compound
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
analysis of transition states via stopped-flow spectroscopy
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
analysis of transition states via stopped-flow spectroscopy
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
overall reaction
-
-
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
the key structural features that are involved in the substrate and active site interaction are highly conserved, e.g. residues Pro214, Glu235, Trp234, Tyr237, Asn246, and Gln129, substrate binding structure and mechanism, overview
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
reaction mechanism, the reaction of the enzyme with oxygen is fast and takes place within several steps, separated by ephemeral intermediates, two short-lived oxy-compounds OxyI and OxyII
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
reaction mechanism, the reaction of the enzyme with oxygen is fast and takes place within several steps, separated by ephemeral intermediates, two short-lived oxy-compounds OxyI and OxyII
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
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
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
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
reaction mechanism, NO release and transport, overview, NO formation through sequential electron transfer and the oxidation of L-arginine, in the catalytic process, FMN, FAD, and tetrahydrobiopterin are required as coenzymes, and the presence of Ca2+/calmodulin can aid the electron transfer, isozymes NOS1 and NOS3 perform a similar reaction mechanism
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
reaction and kinetic mechanism
-
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
reaction and kinetic mechanism
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
MetaCyc
nitric oxide biosynthesis II (mammals)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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).
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
125978-95-2
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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 + ?
Substrates: -
Products: -
Products: -
ir
1-butyl-2-hydroxyguanidine + NADPH + O2
? + NO + NADP+
Substrates: -
Products: -
Products: -
?
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 + ?
Substrates: -
Products: -
Products: -
ir
2-hydroxy-1-(4-hydroxyphenyl)guanidine + NADPH + O2
? + NO + NADP+
Substrates: -
Products: -
Products: -
?
2-hydroxy-1-isopropylguanidine + NADPH + O2
? + NO + NADP+
Substrates: -
Products: -
Products: -
?
ferricytochrome c + NADPH + O2
ferrocytochrome c + NO + NADP+
-
Substrates: -
Products: -
Products: -
?
L-arginine + H2O2 + tetrahydrobiopterin
? + NO + NADP+
-
Substrates: -
Products: -
Products: -
?
N-hydroxy-L-arginine + H2O2 + tetrahydrobiopterin
? + NADP+
-
Substrates: -
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + H2O2
citrulline + Ndelta-cyanoornithine + NO2- + NO3-
-
Substrates: tetrahydrobiopterin-free
Products: NO2-/NO3- as aerobic decomposition products from NO-
Products: NO2-/NO3- as aerobic decomposition products from NO-
?
Nomega-hydroxy-L-arginine + 2',3'-dialdehyde-NADPH + H+ + O2
2 L-citrulline + nitric oxide + 2',3'-dialdehyde-NADP+ + H2O
-
Substrates: -
Products: -
Products: -
r
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
L-citrulline + NADP+ + NO + H2O
-
Substrates: second half reaction
Products: -
Products: -
?
peroxynitrite + 4-hydroxyphenylacetic acid + NADPH + H+
4-hydroxyl-3-nitro-phenylacetic acid + NADP+ + H2O
-
Substrates: oxidation and nitration, although H4B binding seems unable to affect iNOSoxy capacity to activate peroxynitrite decomposition, the binding of Arg and citrulline at the distal side of the heme pocket drastically reduces peroxynitrite activation
Products: product dimers
Products: product dimers
?
2 L-arginine + 2 NADPH + 2 H+ + 2 O2
2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
-
Substrates: first half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
2 L-arginine + 2 NADPH + 2 H+ + 2 O2
2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
-
Substrates: first half reaction via intermediate Nomega-hydroxy-L-arginine with consecutive appearance of heme-dioxy, ferric heme-NO, and ferric heme species, overview
Products: -
Products: -
?
2 L-arginine + 2 NADPH + 2 H+ + 2 O2
2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
-
Substrates: first half reaction
Products: -
Products: -
ir
2 L-arginine + 2 NADPH + 2 H+ + 2 O2
2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
-
Substrates: first half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
2 L-arginine + 2 NADPH + 2 H+ + 2 O2
2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
Substrates: first half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
2 L-arginine + 2 NADPH + 2 H+ + 2 O2
2 Nomega-hydroxy-L-arginine + 2 NADP+ + 2 H2O
-
Substrates: first half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction, two-step oxidation of L-arginine using an O2-dependent mechanism, detailed overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction, the interactions between heme-bound NO and the substrates are finely tuned by the geometry of the Fe-ligand structure, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: NO is an important signalling molecule, released by numerous cells, that acts in many tissues to regulate a diverse range of physiological and biological processes, including neurotransmission, immune defence and the regulation of apoptosis. NO plays a major role in the killing of intracellular pathogens as part of the innate immune response
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: the electron transfer between cofactors FMN and FAD is reversible
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: regulatory mechanism, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: conserved residue Arg1329 of nNOS enables bound NADPH to stabilize the FMN-shielded conformation, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: NO from acetylsalicylic acid-activated enzyme is involved in thrombolysis, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: NOS catalyzes the formation of NO via a consecutive two-step reaction. In the first step, L-arginine is converted to N-hydroxy-L-arginine, in the second step, N-hydroxy-L-arginine is further converted to citrulline and nitric oxide, two different mechanisms, overview. During catalysis, mediated by calcium/calmodulin, electrons flow from NADPH through FAD and FMN in the reductase domain of one subunit of the homodimer to the oxygenase domain of the other subunit, substrate-ligand interaction in the Fe2+-O2 complex, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: substrate and product binding analysis
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: complete reaction, oxygen stoichiometry, effects of substrate/cofactor binding on the endothelial NOS isoform, eNOS, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: complete reaction, during Arg hydroxylation, H4B acts as a one-electron donor and is then presumed to redox cycle, i.e. be reduced back to H4B, within NOS before further catalysis can proceed. Calmodulin-dependent reduction of a tetrahydrobiopterin radical, mechanism involving the NOS flavoprotein domain, reaction scheme, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: conversion of L-arginine to citrulline and nitric oxide takes place in two steps with N(G)-hydroxy-L-arginine as an intermediate product
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction, two-step oxidation of L-arginine using an O2-dependent mechanism, detailed overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction, the interactions between heme-bound NO and the substrates are finely tuned by the geometry of the Fe-ligand structure, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: the enzyme plays an important role in host defense system by catalyzing the production of nitric oxide
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: the enzyme forms a five-coordinate, high-spin complex with L-arginine and analogues, e.g. N-hydroxy-L-arginine
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: a cytokine-inducible, calcium independent and a constitutive, calcium dependent form
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
440193, 440195, 440200, 440201, 440204, 440206, 440209, 440217, 440225, 440226, 440234, 440236, 440238, 440239
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: probably via Nomega-hydroxy-L-arginine
Products: probably via Nomega-hydroxy-L-arginine
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: the overall reaction proceeds via 2 partial reactions: reaction 1 converts L-arginine into L-Ngamma-hydroxyarginine, reaction 2 converts L-Ngamma-hydroxyarginine into citrulline and nitric oxide
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: capacity to synthesize NO only through dimerization and binding of heme and tetrahydrobiopterin
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: dimeric structure is required for enzyme activity
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: dimeric structure is required for enzyme activity
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: tetrahydrobiopterin is absolutely required for partial reaction 1
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: specific for NADPH, 5-electron oxidation of L-arginine
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: enzyme of mammalian immune, cardiovascular and neural systems, synthesizing the free radical nitric oxide or a NO-releasing product
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: soluble cytochrome P-450 enzyme in eukaryotes
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: probably via Nomega-hydroxy-L-arginine
Products: probably via Nomega-hydroxy-L-arginine
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: guanidino-nitrogen of L-arginine is oxidized to form NO and citrulline
Products: guanidino-nitrogen of L-arginine is oxidized to form NO and citrulline
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: the overall reaction proceeds via 2 partial reactions: reaction 1 converts L-arginine into L-Ngamma-hydroxyarginine, reaction 2 converts L-Ngamma-hydroxyarginine into citrulline and nitric oxide
Products: -
Products: -
ir
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: specific for NADPH, 5-electron oxidation of L-arginine
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: soluble cytochrome P-450 enzyme in eukaryotes
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: mitochondrial nitric oxide production is involved in modulation of several organelle functions, such as transmembrane potential and matrix pH, inhibition of respiration by competitive inhibition with oxygen in cytochrome c oxidase, inhibition of ATP synthesis, permeability transition pore (PTP) opening, apoptosis and cell death, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
Products: the product is a guanylyl-cyclase-relaxing factor, that is identical with nitric oxide or a NO-releasing compound
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2,6-dichlorophenolindophenol + NADPH + O2
? + NO + NADP+
-
Substrates: best substrate, about 10-fold increase in activity in presence of calmodulin
Products: -
Products: -
?
2,6-dichlorophenolindophenol + NADPH + O2
? + NO + NADP+
-
Substrates: -
Products: -
Products: -
?
2,6-dichlorophenolindophenol + NADPH + O2
? + NO + NADP+
-
Substrates: -
Products: -
Products: -
?
ferricyanide + NADPH + O2
ferrocyanide + NADP+ + ?
-
Substrates: -
Products: -
Products: -
?
L-Ala-L-Arg + NADPH + O2
?
-
Substrates: endothelial microsomes, macrophage
Products: -
Products: -
?
L-Ala-L-Arg + NADPH + O2
?
-
Substrates: endothelial microsomes, macrophage
Products: -
Products: -
?
L-Arg-L-Arg + NADPH + O2
?
-
Substrates: endothelial, microsomes, macrophage
Products: -
Products: -
?
L-Arg-L-Arg + NADPH + O2
?
-
Substrates: endothelial, microsomes, macrophage
Products: -
Products: -
?
L-Arg-L-Arg-L-Arg + NADPH + O2
?
-
Substrates: endothelial microsomes
Products: -
Products: -
?
L-Arg-L-Arg-L-Arg + NADPH + O2
?
-
Substrates: endothelial microsomes
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: synthesis of the signaling molecule nitric oxide
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: nitric-oxide synthase (NOS) is required in mammals to generate nitric-oxide for regulating blood pressure, synaptic response, and immune defense
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: proposed conformational model for nitric oxide synthesis by the enzyme. Nitric oxide synthesis involves two distinct changes in the holoenzyme complex: 1. an extended-to-closed conformational equilibrium that brings the reductase domains together in a cross-monomer arrangement, and 2. release and rotation of the FMN domain triggered by CaM binding that positions the FMN cofactor for electron transfer across to the adjacent oxygenase domain in the closed state
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
Substrates: -
Products: -
Products: -
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
Substrates: -
Products: -
Products: -
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
Substrates: -
Products: -
Products: -
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
Substrates: -
Products: -
Products: -
?
L-homoarginine + NADPH + O2
?
-
Substrates: constitutive endothelial membrane-bound and inducible soluble macrophage enzyme
Products: -
Products: -
?
L-homoarginine + NADPH + O2
?
-
Substrates: constitutive endothelial membrane-bound and inducible soluble macrophage enzyme
Products: -
Products: -
?
L-homoarginine + NADPH + O2
?
-
Substrates: poor substrate
Products: -
Products: -
?
N-hydroxy-L-arginine + NADPH + O2
? + NO + NADP+
Substrates: -
Products: -
Products: -
?
N-hydroxy-L-arginine + NADPH + O2
? + NO + NADP+
Substrates: -
Products: -
Products: -
?
N-hydroxy-L-arginine + NADPH + O2
? + NO + NADP+
Substrates: -
Products: -
Products: -
?
N-hydroxy-L-arginine + NADPH + O2
? + NO + NADP+
-
Substrates: -
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: -
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: best substrate
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: -
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: substrate is intermediate between reaction 1 and 2 to form citrulline and NO from L-arginine
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: reaction is possible without tetrahydrobiopterin, can also use H2O2 instead of NADPH and O2
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: -
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: best substrate
Products: -
Products: -
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
Substrates: substrate is intermediate between reaction 1 and 2 to form citrulline and NO from L-arginine
Products: -
Products: -
ir
nitroblue tetrazolium + 2 NADPH
nitroblue tetrazolium formazan + 2 NADP+
-
Substrates: NADPH-diaphorase reaction
Products: -
Products: -
?
nitroblue tetrazolium + 2 NADPH
nitroblue tetrazolium formazan + 2 NADP+
-
Substrates: NADPH-diaphorase reaction
Products: -
Products: -
?
nitroblue tetrazolium + 2 NADPH
nitroblue tetrazolium formazan + 2 NADP+
-
Substrates: -
Products: -
Products: -
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
Substrates: second half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
Substrates: second half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
Substrates: second half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
Substrates: second half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
Substrates: second half reaction via intermediate Nomega-hydroxy-L-arginine
Products: -
Products: -
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
Substrates: second half reaction via intermediate Nomega-hydroxy-L-arginine, FeII and FeII-NO complexes bind Nomega-hydroxy-L-arginine, overview
Products: -
Products: -
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
Substrates: -
Products: -
Products: -
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
Substrates: -
Products: -
Products: -
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
Substrates: -
Products: -
Products: -
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
Substrates: -
Products: -
Products: -
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
Substrates: -
Products: -
Products: -
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
Substrates: wild-type and mutants
Products: -
Products: -
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
Substrates: reaction is enhanced by addition of calmodulin at 0.0002 mM
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is involved in a multi-turnover process that results in NO as a product, NO is important in various pathological and physiological processes, NO produced by Bacillus anthracis may also have a pivotal pathophysiological role in anthrax infection
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bacterial enzyme, bNOS, lacks an essential reductase domain, that supplies electrons during NO biosynthesis, and is thus limited with respect to a pool of available redox partners, but does produce NO in living cells and accomplish this task by hijacking available cellular redox partners that are not normally committed to NO production, bacterial reductase also supports NO synthesis by the oxygenase domain of mammalian NOS expressed in Escherichia coli, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bacterial enzyme, bNOS, lacks an essential reductase domain, that supplies electrons during NO biosynthesis, and is thus limited with respect to a pool of available redox partners, but does produce NO in living cells and accomplish this task by hijacking available cellular redox partners that are not normally committed to NO production, bacterial reductase also supports NO synthesis by the oxygenase domain of mammalian NOS expressed in Escherichia coli, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: mechanisms of oxygen activation by NOSs, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bacterial NOS enzymes have no attached flavoprotein domain to reduce their heme and so must rely on unknown bacterial proteins for electrons
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme shows also superoxide formation activity, uneffected by L-arginine, inhibited by tetrahydrobiopterin and diphenyleneiodonium
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme shows also superoxide formation activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: endothelial NOS has a 6fold lower NO synthesis activity and 6-16fold lower cytochrome c reductase activity than neuronal NOS due to a significantly different electron transfer capacities, substrate specificity and mechanism, oveview
Products: -
Products: -
?
additional information
?
-
-
Substrates: postsynaptic density 95 proteins mediate the complex formation of neuronal nitric oxide synthase and N-methyl-D-aspartate receptors
Products: -
Products: -
?
additional information
?
-
-
Substrates: Drosophila dNOS is a more efficient and active NO synthase than the mammalian NOS enzymes, which may allow it to function more broadly in cell signaling and immune functions in the fruit fly
Products: -
Products: -
?
additional information
?
-
-
Substrates: dNOS participates in essential developmental and behavioral aspects of the fruit fly
Products: -
Products: -
?
additional information
?
-
-
Substrates: a oxygenase domain of dNOS complex with ferrous heme-NO is relatively unreactive toward O2
Products: -
Products: -
?
additional information
?
-
-
Substrates: crude, boiled or ethanolic and dried extracts of Ganoderma applanatum show antioxidant activity, inhibition of lipid peroxidation, and potent hydroxylradical scavenging activity, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme can also Ca2+/calmodulin-dependently produce superoxide in absence of tetrahydropterin and in depletion of L-arginine, which is inhibited by tetrahydropterin, cyanide and imidazole
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
-
Substrates: neuronal NO synthase may be involved in the pathogenesis of acute lung injury after smoke inhalation injury followed by bacterial instillation in the airway
Products: -
Products: -
?
additional information
?
-
-
Substrates: Pseudomonas aeruginosa stimulates expression of inducible nitric oxide synthase by A-549 cells. NO may be the mediator of epithelial damage caused by Pseudomonas aeruginosa
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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, genetic, endothelial-specific regulation model, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: genetic regulation, mechanism, eNOS expression is controlled by both histone acetylation and lysine 4 methylation of histone H3 at eNOS proximal promoter regions, overview
Products: -
Products: -
?
additional information
?
-
Substrates: calmodulin-controlled isoforms are signal generators, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme interacts with Vac14, the activator of the PtdIns(3)P 5-kinase PIKfyve, the beta-finger independent interaction is based on an internal motif, sequence -G-D-H-L-D-, for PDZ recognition, PDZ domains are protein interaction modules found in single or multiple copies in a variety of proteins involved in multiprotein signaling complexes, interaction study with wild-type and mutant Vac14 proteins, binding is not abolished by deletion of the last five amino acids, but is abolished with deletions of the last 53 or last 10 residues of Vac14, overview
Products: -
Products: -
?
additional information
?
-
Substrates: both oxyFMN and oxygenase domain activity are measured by following H2O2-supported oxidation of Nomega-hydroxy-L-Arg, L-NOHA, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: NOS has also nitrite reductase activity, the release of free nitric oxide from anoxic nitrite solutions at 0.015 mM is specific to the eNOS isoform and does not occur with the nNOS or iNOS isoforms
Products: -
Products: -
?
additional information
?
-
Substrates: NOS has also nitrite reductase activity, the release of free nitric oxide from anoxic nitrite solutions at 0.015 mM is specific to the eNOS isoform and does not occur with the nNOS or iNOS isoforms
Products: -
Products: -
?
additional information
?
-
Substrates: NOS has also nitrite reductase activity, the release of free nitric oxide from anoxic nitrite solutions at 0.015 mM is specific to the eNOS isoform and does not occur with the nNOS or iNOS isoforms
Products: -
Products: -
?
additional information
?
-
Substrates: the bioavailability of substrates (L-arginine and O2) and the cofactor BH4 are important elements of enzyme activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bioavailability of substrates (L-arginine and O2) and the cofactor BH4 are important elements of enzyme activity
Products: -
Products: -
?
additional information
?
-
Substrates: each monomer contains an oxygenase domain in the N-terminal section and a reductase domain in the C-terminal section. The oxygenase domain has binding sites for FAD, FMN and NADPH and is linked through a calmodulin recognition site to the reductase domain which has binding sites for heme, tetrahydrobiopterin (BH4), and L-arginine. In functional NOS, electrons are released by NADPH in the reductase domain and are transferred through FAD and FMN to the heme group of the opposite dimer. At this point, in the presence of L-arginine and the cofactor BH4, the electrons enable the reduction of O2 and the formation of NO and L-citrulline. The formation of NO requires electron flow, starting at the flavin level in the reductase domain, and ending at the heme level, on the oxygenase domain of the enzyme. The oxidized heme is able to bind O2 and L-arginine to synthesize NO and L-citrulline
Products: -
Products: -
?
additional information
?
-
-
Substrates: each monomer contains an oxygenase domain in the N-terminal section and a reductase domain in the C-terminal section. The oxygenase domain has binding sites for FAD, FMN and NADPH and is linked through a calmodulin recognition site to the reductase domain which has binding sites for heme, tetrahydrobiopterin (BH4), and L-arginine. In functional NOS, electrons are released by NADPH in the reductase domain and are transferred through FAD and FMN to the heme group of the opposite dimer. At this point, in the presence of L-arginine and the cofactor BH4, the electrons enable the reduction of O2 and the formation of NO and L-citrulline. The formation of NO requires electron flow, starting at the flavin level in the reductase domain, and ending at the heme level, on the oxygenase domain of the enzyme. The oxidized heme is able to bind O2 and L-arginine to synthesize NO and L-citrulline
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme might be involved in the infectivity and/or escaping mechanism of the parasite
Products: -
Products: -
?
additional information
?
-
-
Substrates: Ngamma-hydroxylation is the first step of the reaction, Ngamma-hydroxy-L-arginine being an intermediate in the L-arginine to NO pathway
Products: -
Products: -
?
additional information
?
-
-
Substrates: dimeric enzyme and subunits are equivalent in catalyzing electron transfer from NADPH to cytochrome c, dichlorophenolindiphenol, and ferricyanide
Products: -
Products: -
?
additional information
?
-
-
Substrates: D-arginine is no substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: calmodulin-controlled isoforms are signal generators, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: both oxyFMN and oxygenase domain activity are measured by following H2O2-supported oxidation of Nomega-hydroxy-L-Arg, L-NOHA, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: iNOS modulates endothelin-1-dependent release of prostacyclin and inhibition of platelet aggregation ex vivo in the mouse, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: inducible nitric-oxide synthase-derived NO contributes to the pathophysiology of intestinal inflammation in the colon
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme exclusively performs the nitric oxide synthesis, an essential biological mediator, and of peroxynitrite, a well known cytotoxic agent involved innumerouspathophysiological processes, NOSs have the unique ability to both produce and activate peroxynitrite, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: nitric-oxide synthase 2 interacts with CD74 and inhibits its cleavage by caspase during dendritic cell development
Products: -
Products: -
?
additional information
?
-
-
Substrates: interaction between peroxynitrite and the oxygenase domain of inducible NOS
Products: -
Products: -
?
additional information
?
-
Substrates: eNOS is an important negative regulator of AMP-activated protein kinase phosphorylation and intracellular H2O2 generation in endothelial cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme exhibits NADPH-diaphorase activity, uncoupled from nitric oxide synthase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: D-arginine is no substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
Substrates: calmodulin-controlled isoforms are signal generators, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: caveolin-1 is a prominent NOS-interacting protein in rat polymorphonuclear neutrophils
Products: -
Products: -
?
additional information
?
-
Substrates: NO is implicated in the pathogenesis of liver cirrhosis, overview
Products: -
Products: -
?
additional information
?
-
Substrates: both oxyFMN and oxygenase domain activity are measured by following H2O2-supported oxidation of Nomega-hydroxy-L-Arg, L-NOHA, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: eNOS uncoupling is known to be controlled by substrate/cofactor availability, and the uncoupled reactions play important roles under various physiological/pathological conditions, such as atherosclerosis and septic shock
Products: -
Products: -
?
additional information
?
-
-
Substrates: increased iNOS expression due to ethanol intake is responsible for gender differences in the vascular effects elicited by chronic ethanol consumption, while ovarian hormones do not play a role, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: three unique structural elements are involved in the catalytic suppression of NOS: an autoinhibitory element in the FMN binding module, a CD2A loop in the connecting subdomain, and a C-terminal extension or tail, the C-terminal tail of nNOS is a regulatory element that suppresses nNOS activities in the absence of bound calmodulin, it may help stabilize the FMN-shielded conformation by holding the FMN module up against the FNR module as required for inter-flavin electron transfer, mechanism, overview
Products: -
Products: -
?
additional information
?
-
Substrates: nitric-oxide synthases are catalytically self-sufficient flavo-heme enzymes that generate NO from L-arginine and display an utilization of their tetrahydrobiopterin cofactor, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the reduced recombinant trunaction mutant nNOSr performs autooxidation in presence of NADPH, interactions, overview
Products: -
Products: -
?
additional information
?
-
Substrates: the similar spatial distribution of NADPH diaphorase and nitric oxide synthase (NOS) in aldehyde-treated tissues has lead to the postulation that the catalytic activity of NOS promotes NADPH-dependent reduction of nitro-blue tetrazolium (NBT) to insoluble readily visualized diformazan particles. Since NADPH cannot directly reduce NBT, it is argued that NBT binds to NOS at the flavin electron transport domain and is reduced by a NOS form, which is previously reduced by beta-NADPH. However, paraformaldehyde fixation of rat brain abolishes NOS activity in particulate and cytosolic fractions and although fixation abolishes NADPH diaphorase in the particulate fraction, 50-60% of NADPH diaphorase activity remains in the cytosolic fraction. This suggests that cytosolic NADPH diaphorase in aldehyde-treated tissues results from a factor other than NOS. NOS contains heme iron, flavin adenine dinucleotide and flavin mononucleotide. NADPH-dependent reduction of NBT in aldehyde-treated tissues is not directly due to NOS because metal chelators that inhibit activity of metalloenzymes and deflavinating agents do not eliminate NADPH diaphorase. While the NOS active site is not required to promote the NADPH-dependent reduction of NBT, some other reactive site of the protein could still be involved. SNOs exist in cytoplasmic vesicles of endothelial cells of rat small mesenteric arteries, SNOs promote the NADPH-dependent reduction of NBT, both alpha-NADPH and beta-NADPH promote the reduction of NBT to diformazan and since alpha-NADPH will not donate electrons to NOS, it is unlikely that diformazan is the result of an increase in the catalytic activity of NOS, prior depletion of SNOs in tissues markedly reduces subsequent NADPH diaphorase staining. NADPH diaphorase activity in aldehyde-treated tissues is due to preformed pools of SNOs that facilitate NADPH-dependent reduction of NBT to diformazan
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme exhibits NADPH-diaphorase activity, uncoupled from nitric oxide synthase activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
Substrates: the similar spatial distribution of NADPH diaphorase and nitric oxide synthase (NOS) in aldehyde-treated tissues has lead to the postulation that the catalytic activity of NOS promotes NADPH-dependent reduction of nitro-blue tetrazolium (NBT) to insoluble readily visualized diformazan particles. Since NADPH cannot directly reduce NBT, it is argued that NBT binds to NOS at the flavin electron transport domain and is reduced by a NOS form, which is previously reduced by beta-NADPH. However, paraformaldehyde fixation of rat brain abolishes NOS activity in particulate and cytosolic fractions and although fixation abolishes NADPH diaphorase in the particulate fraction, 50-60% of NADPH diaphorase activity remains in the cytosolic fraction. This suggests that cytosolic NADPH diaphorase in aldehyde-treated tissues results from a factor other than NOS. NOS contains heme iron, flavin adenine dinucleotide and flavin mononucleotide. NADPH-dependent reduction of NBT in aldehyde-treated tissues is not directly due to NOS because metal chelators that inhibit activity of metalloenzymes and deflavinating agents do not eliminate NADPH diaphorase. While the NOS active site is not required to promote the NADPH-dependent reduction of NBT, some other reactive site of the protein could still be involved. SNOs exist in cytoplasmic vesicles of endothelial cells of rat small mesenteric arteries, SNOs promote the NADPH-dependent reduction of NBT, both alpha-NADPH and beta-NADPH promote the reduction of NBT to diformazan and since alpha-NADPH will not donate electrons to NOS, it is unlikely that diformazan is the result of an increase in the catalytic activity of NOS, prior depletion of SNOs in tissues markedly reduces subsequent NADPH diaphorase staining. NADPH diaphorase activity in aldehyde-treated tissues is due to preformed pools of SNOs that facilitate NADPH-dependent reduction of NBT to diformazan
Products: -
Products: -
?
additional information
?
-
-
Substrates: D-arginine is no substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: mechanisms of oxygen activation by NOSs, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the reductase domain has a broad substrate specificity, catalyzes a moderate Ca2+/calmodulin independent hydroxylation when the enzyme is reconstituted with purified P-450
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: NO is an important signalling molecule, released by numerous cells, that acts in many tissues to regulate a diverse range of physiological and biological processes, including neurotransmission, immune defence and the regulation of apoptosis. NO plays a major role in the killing of intracellular pathogens as part of the innate immune response
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: regulatory mechanism, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: NO from acetylsalicylic acid-activated enzyme is involved in thrombolysis, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: the enzyme plays an important role in host defense system by catalyzing the production of nitric oxide
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: a cytokine-inducible, calcium independent and a constitutive, calcium dependent form
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: enzyme of mammalian immune, cardiovascular and neural systems, synthesizing the free radical nitric oxide or a NO-releasing product
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: soluble cytochrome P-450 enzyme in eukaryotes
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: soluble cytochrome P-450 enzyme in eukaryotes
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: mitochondrial nitric oxide production is involved in modulation of several organelle functions, such as transmembrane potential and matrix pH, inhibition of respiration by competitive inhibition with oxygen in cytochrome c oxidase, inhibition of ATP synthesis, permeability transition pore (PTP) opening, apoptosis and cell death, overview
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: -
Products: -
Products: -
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
Substrates: physiological functions and pathophysiology of the isoforms
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: synthesis of the signaling molecule nitric oxide
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: nitric-oxide synthase (NOS) is required in mammals to generate nitric-oxide for regulating blood pressure, synaptic response, and immune defense
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
L-arginine + 3 NADPH + 3 H+ + 4 O2
2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
Substrates: overall reaction
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme is involved in a multi-turnover process that results in NO as a product, NO is important in various pathological and physiological processes, NO produced by Bacillus anthracis may also have a pivotal pathophysiological role in anthrax infection
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bacterial enzyme, bNOS, lacks an essential reductase domain, that supplies electrons during NO biosynthesis, and is thus limited with respect to a pool of available redox partners, but does produce NO in living cells and accomplish this task by hijacking available cellular redox partners that are not normally committed to NO production, bacterial reductase also supports NO synthesis by the oxygenase domain of mammalian NOS expressed in Escherichia coli, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bacterial enzyme, bNOS, lacks an essential reductase domain, that supplies electrons during NO biosynthesis, and is thus limited with respect to a pool of available redox partners, but does produce NO in living cells and accomplish this task by hijacking available cellular redox partners that are not normally committed to NO production, bacterial reductase also supports NO synthesis by the oxygenase domain of mammalian NOS expressed in Escherichia coli, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme shows also superoxide formation activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: postsynaptic density 95 proteins mediate the complex formation of neuronal nitric oxide synthase and N-methyl-D-aspartate receptors
Products: -
Products: -
?
additional information
?
-
-
Substrates: Drosophila dNOS is a more efficient and active NO synthase than the mammalian NOS enzymes, which may allow it to function more broadly in cell signaling and immune functions in the fruit fly
Products: -
Products: -
?
additional information
?
-
-
Substrates: dNOS participates in essential developmental and behavioral aspects of the fruit fly
Products: -
Products: -
?
additional information
?
-
-
Substrates: crude, boiled or ethanolic and dried extracts of Ganoderma applanatum show antioxidant activity, inhibition of lipid peroxidation, and potent hydroxylradical scavenging activity, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
-
Substrates: neuronal NO synthase may be involved in the pathogenesis of acute lung injury after smoke inhalation injury followed by bacterial instillation in the airway
Products: -
Products: -
?
additional information
?
-
-
Substrates: Pseudomonas aeruginosa stimulates expression of inducible nitric oxide synthase by A-549 cells. NO may be the mediator of epithelial damage caused by Pseudomonas aeruginosa
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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, genetic, endothelial-specific regulation model, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: genetic regulation, mechanism, eNOS expression is controlled by both histone acetylation and lysine 4 methylation of histone H3 at eNOS proximal promoter regions, overview
Products: -
Products: -
?
additional information
?
-
Substrates: calmodulin-controlled isoforms are signal generators, overview
Products: -
Products: -
?
additional information
?
-
Substrates: the bioavailability of substrates (L-arginine and O2) and the cofactor BH4 are important elements of enzyme activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bioavailability of substrates (L-arginine and O2) and the cofactor BH4 are important elements of enzyme activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme might be involved in the infectivity and/or escaping mechanism of the parasite
Products: -
Products: -
?
additional information
?
-
-
Substrates: calmodulin-controlled isoforms are signal generators, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: iNOS modulates endothelin-1-dependent release of prostacyclin and inhibition of platelet aggregation ex vivo in the mouse, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: inducible nitric-oxide synthase-derived NO contributes to the pathophysiology of intestinal inflammation in the colon
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme exclusively performs the nitric oxide synthesis, an essential biological mediator, and of peroxynitrite, a well known cytotoxic agent involved innumerouspathophysiological processes, NOSs have the unique ability to both produce and activate peroxynitrite, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: nitric-oxide synthase 2 interacts with CD74 and inhibits its cleavage by caspase during dendritic cell development
Products: -
Products: -
?
additional information
?
-
Substrates: eNOS is an important negative regulator of AMP-activated protein kinase phosphorylation and intracellular H2O2 generation in endothelial cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
Substrates: calmodulin-controlled isoforms are signal generators, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: caveolin-1 is a prominent NOS-interacting protein in rat polymorphonuclear neutrophils
Products: -
Products: -
?
additional information
?
-
Substrates: NO is implicated in the pathogenesis of liver cirrhosis, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: eNOS uncoupling is known to be controlled by substrate/cofactor availability, and the uncoupled reactions play important roles under various physiological/pathological conditions, such as atherosclerosis and septic shock
Products: -
Products: -
?
additional information
?
-
-
Substrates: increased iNOS expression due to ethanol intake is responsible for gender differences in the vascular effects elicited by chronic ethanol consumption, while ovarian hormones do not play a role, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: three unique structural elements are involved in the catalytic suppression of NOS: an autoinhibitory element in the FMN binding module, a CD2A loop in the connecting subdomain, and a C-terminal extension or tail, the C-terminal tail of nNOS is a regulatory element that suppresses nNOS activities in the absence of bound calmodulin, it may help stabilize the FMN-shielded conformation by holding the FMN module up against the FNR module as required for inter-flavin electron transfer, mechanism, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
additional information
?
-
-
Substrates: NO represents the endogenous activator of soluble guanylyl cyclase
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2',3'-dialdehyde analogue of NADPH
-
activation, can substitute for NADPH at low concentrations, inhibitory at concentrations of 40times the apparent Km-value or after prolonged incubation
flavodoxin
-
reduced YkuN and YkuP containing FMN, YkuN is more efficient in supporting bsNOS catalysis, Km for YkuN is 0.0016 mM, for YkuP 0.022 mM, overview
-
5,6,7,8-tetrahydro-L-biopterin
-
enzyme purified in absence of biopterin contains substoichiometric concentration, if purified in presence of biopterin it contains 1 mol biopterin per mol MW 130000 subunit
5,6,7,8-tetrahydro-L-biopterin
-
absolute requirement, recombinant from Pichia pastoris
5,6,7,8-tetrahydro-L-biopterin
-
activity is correlated directly to bound biopterin concentration
5,6,7,8-tetrahydro-L-biopterin
-
required for the first partial reaction, formation of NG-hydroxy-L-arginine
5,6,7,8-tetrahydro-L-biopterin
-
i.e. (6R)-2-amino-4-hydroxy-6-(L-erythro-1,2-dihydroxypropyl)-5,6,7,8-tetrahydropteridine, 6R-isomer, requirement, biopteroflavoprotein, 1 mol tetrahydrobiopterin per mol enzyme dimer
Calmodulin
-
the enzyme bears a Ca2+/calmodulin dependent FAD and FMN containing reductase domain which transfers electrons from NADPH to a variety of acceptors
Calmodulin
-
activation, potent stimulator of purified, not crude, enzyme preparation
Calmodulin
-
Ca2+/calmodulin is required for superoxide formation in absence of tetrahydropterin
Calmodulin
-
no stimulation with exogenous calmodulin, inducible isoform from liver
Calmodulin
-
15fold stimulation of cytochrome c reduction of wild-type and mutants C415A and C415H
Calmodulin
-
NADPH-diaphorase activity of the enzyme is Ca2+/calmodulin independent
Calmodulin
-
enzyme-bound, the binding sequence links the two enzyme domains
Calmodulin
in the absence of calmodulin, the wild type enzyme activity is less than 15% of the maximum calmodulin-dependent values
Calmodulin
maximum calmodulin-dependent activity is measured at 1.5 mM CaCl2, phosphorylation within an autoinhibitory domain in endothelial nitric oxide synthase reduces the Ca2+ concentrations required for calmodulin to bind and activate the enzyme
FAD
-
the enzyme bears Ca2+/calmodulin dependent FAD and FMN containing reductase domain which transfers electrons from NADPH to a variety of acceptors
FAD
-
electron flow within the neuronal nitric oxide synthase reductase domain includes hydride transfer from NADPH to FAD followed by two one-electron transfer reactions from FAD to FMN. Binding of the second NADPH is necessary to drive the full reduction of FMN and charge transfer and the subsequent interflavin electron transfer have distinct spectral features that can be monitored separately with stopped flow spectroscopy. Interflavin electron transfer reported at 600 nm is not limiting in nitric oxide synthase catalysis
FAD
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
FAD
during catalysis, NADPH-derived electrons are transfered into FAD and then distributed into the FMN domain for further transfer to internal or external heme groups. Conformational freedom of the FMN domain is essential for the electron transfer
FMN
-
wild-type and mutant C415H contain 0.8 and 0.9 mol per mol of subunit, respectively
FMN
-
the enzyme bears Ca2+/calmodulin dependent FAD and FMN containing reductase domain which transfers electrons from NADPH to a variety of acceptors
FMN
FMN/heme electron transfer, FMN is capable of serving as a one electron heme reductant
FMN
-
FMN/heme electron transfer, FMN is capable of serving as a one electron heme reductant
FMN
FMN/heme electron transfer, FMN is capable of serving as a one electron heme reductant
FMN
-
regulation of the FMN module conformational equilibrium, overview
FMN
-
an inverse correlation exists between FMN shielding and the cytochrome c reductase activity
FMN
-
determination of FMN-heme intraprotein electron transfer kinetics in full length and oxygenase/FMN construct of human inducible nitric oxide synthase. The rate constant increases considerably with temperature. The FMN domain in the holoenzyme needs to sample more conformations before the intraprotein electron transfer takes place, and the FMN domain in the oxyFMN construct is better poised for efficient intraprotein electron transfer
FMN
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
FMN
during catalysis, NADPH-derived electrons are transfer into FAD and then distributed into the FMN domain for further transfer to internal or external heme groups. Conformational freedom of the FMN domain is essential for the electron transfer
FMN
proposed conformational model for nitric oxide synthesis by the enzyme. Nitric oxide synthesis involves two distinct changes in the holoenzyme complex: 1. an extended-to-closed conformational equilibrium that brings the reductase domains together in a cross-monomer arrangement, and 2. release and rotation of the FMN domain triggered by CaM binding that positions the FMN cofactor for electron transfer across to the adjacent oxygenase domain in the closed state
heme
-
an inverse correlation exists between FMN shielding and the cytochrome c reductase activity
heme
-
the heme is coordinated by a cysteine residue on the proximal side, and the substrates, Arg or N-hydroxy-L-arginine, bind above the heme iron atom in the distal pocket, while the cofactor, tetrahydrobiopterin, binds along the side of the heme
NADPH
-
-
NADPH
-
requirement, specific for, NADPH-diaphorase activity requires higher NADPH concentrations than nitric oxide formation
NADPH
-
binding structure of NADP(H) to wild-type and truncation mutant enzyme lacking parts of the C-terminus, overview
NADPH
-
electron flow within the neuronal nitric oxide synthase reductase domain includes hydride transfer from NADPH to FAD followed by two one-electron transfer reactions from FAD to FMN. Binding of the second NADPH is necessary to drive the full reduction of FMN and charge transfer and the subsequent interflavin electron transfer have distinct spectral features that can be monitored separately with stopped flow spectroscopy. Interflavin electron transfer reported at 600 nm is not limiting in nitric oxide synthase catalysis
NADPH
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
NADPH
provided from the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH diaphorase) activity. In the brain, NADPH diaphorase (NADPH-d) and nNOS are strictly co-localized
tetrahydrobiopterin
-
oxidation product of BH4 is a protonated BH3 radical, key role of BH4 in protonation of Fe(II)-O2-, overview
tetrahydrobiopterin
-
oxidation product of BH4 is a protonated BH3 radical, key role of BH4 in protonation of Fe(II)-O2-, overview
tetrahydrobiopterin
-
the cofactor tetrahydrobiopterin binds along the side of the heme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+/calmodulin
Fe2+
Iron
Ca2+
-
constitutive endothelial and inducible membrane bound macrophage enzyme are strictly Ca2+-dependent
Ca2+
required for calmodulin to bind and activate the enzyme, maximum calmodulin-dependent activity is measured at 1.5 mM CaCl2
Ca2+
-
Ca2+/calmodulin is required for citrulline/NO formation and for superoxide formation in absence of tetrahydropterin
Ca2+
the raise of intracellular calcium levels increases nNOS dephosphorylation and enzymatic activity
Ca2+
-
constitutive endothelial and inducible membrane bound macrophage enzyme are strictly Ca2+-dependent
Ca2+
-
stimulation of mtNOS can be achieved by elevating mitochondrial Ca2+ (0.01-0.1 mM)
Ca2+
-
the enzyme bears Ca2+/calmodulin dependent cytochrome P-450 reductase activity which catalyzes cytochrome c reduction
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
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
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
Fe2+
-
a heme enzyme, spectral comparison of the FeIII-NO and FeII-NO complexes of the bacterial NOSs, FeIII-NO complexes lack change in Fe-N-O frequencies upon (6R) 5,6,7,8-tetrahydro-L-biopterin binding to bacterial NOSs, overview. In the FeIII-NO complexes, both L-arginine and NOHA induced the Fe-N-O bending mode at nearly the same frequency as a result of a steric interaction between the substrates and the heme-bound NO, while in FeII-NO complexes the the Fe-N-O bending mode is no observed
Fe2+
-
in the heme cofactor, substrate-ligand interaction in the Fe2+-O2 complex, overview
Fe2+
-
a heme enzyme, spectral comparison of the FeIII-NO and FeII-NO complexes of the bacterial NOSs, FeIII-NO complexes lack change in Fe-N-O frequencies upon (6R) 5,6,7,8-tetrahydro-L-biopterin binding to bacterial NOSs, overview. In the FeIII-NO complexes, both L-arginine and NOHA induced the Fe-N-O bending mode at nearly the same frequency as a result of a steric interaction between the substrates and the heme-bound NO, while in FeII-NO complexes the the Fe-N-O bending mode is no observed
Iron
-
as heme iron in protoporphyrin IX /heme, hemesubstrate interactions and heme-transitions, overview
Iron
-
2 mol iron-protoporphyrin IX per mol enzyme dimer, the heme-iron is ferric, EPR-and light absorbance spectroscopy
Iron
-
naturally occuring neuronal mutant with a 105-amino acid deletion in the heme-binding domain as a result of in-frame mutation by specific alternative splicing, contains heme, but shows no L-arginine and NADPH-dependent citrulline-forming activity in presence of Ca2+-promoted calmodulin, the heme coordination geometry is highly abnormal
Iron
low-spin heme iron, L-arginine aud tetrahydrobiopterin bind and stabilize heme iron in five-coordinate high-spin state
Iron
-
2 mol iron-protoporphyrin IX per mol enzyme dimer, the heme-iron is ferric, EPR-and light absorbance spectroscopy
Iron
-
low-spin heme iron, L-arginine and tetrahydrobiopterin bind and stabilize heme iron in five-coordinate high-spin state
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-phenylimidazole
-
reversible inhibition of endothelial enzyme, competitive versus L-arginine and tetrahydrobiopterin, no inhibition of cytochrome c reduction
2',3'-dialdehyde of NADPH
-
at concentrations of 40times the apparent Km-value or after prolonged incubation, independent of Ca2+/calmodulin, L-arginine or tetrahydrobiopterin, NADPH prevents inhibition, the NADPH-diaphorase activity of the enzyme is less sensitive than the nitric oxide synthase activity
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)-6-chloro-1H-quinolin-2-one trifluoroacetic acid salt
IC50: 410 nM, pharmacokinetic profile
4-oxononenal
ONE, a highly bioreactive agent, able to inhibit eNOS activity and NO production. It can posttranslationally modify the enzyme in the placenta
-
5,6,7,8-tetrahydrobiopterin
-
quenches the uncoupled reactions and results in much less reactive oxygen species formation, whereas the presence of redox-incompetent 7,8-dihydrobiopterin demonstrates little quenching effect
6-([[(3R,5S)-5-[[(6-amino-4-methylpyridin-2-yl)methoxy]methyl]pyrrolidin-3-yl]oxy]methyl)-4-methylpyridin-2-amine
exhibits antimicrobial properties
6-n-propyl-2-thyouracil
0.1 mg 6-n-propyl-2-thyouracil decreases nNOS activity to 45% compared to control
6-[[(2S,3S)-2-amino-3-[(6-amino-4-methylpyridin-2-yl)methoxy]butoxy]methyl]-4-methylpyridin-2-amine
exhibits antimicrobial properties
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; causes an increase in NADPH oxidase activity of the enzyme
carbon monoxide
carbon monoxide down-regulates iNOS activity by reducing its expression level or by inhibiting its activity by converting it to an inactive P420 form, the presence of dithiothreitol, L-Arg, or H4B partially inhibits the iNOSP450 to iNOSP420 conversion, whereas the presence of both L-Arg and 5,6,7,8-tetrahydro-L-biopterin completely prevents the transition
Di-2-thienyliodonium
-
competitive, irreversible, complete, time and temperature dependent inhibition
Gly-methyl-L-arginine
-
inhibition of the isozymes in absence or presence of L-arginine
Iodoniumdiphenyl
-
competitive, irreversible, complete, time and temperature dependent inhibition
L-Asn-methyl-L-arginine
-
inhibition of the isozymes in absence or presence of L-arginine
L-N-methylarginine
NOS inhibitor, complete inhibition at 0.5 mM; NOS inhibitor, complete inhibition at 0.5 mM; NOS inhibitor, complete inhibition at 0.5 mM
L-omega-monomethyl L-arginine
potent competitive eNOS inhibitor, complete inhibition at 10 mM
MeHg
methylmercury, impact of chronic MeHg intoxication on NADPH diaphorase (NADPH-d) activity and astrocyte mobilization in the visual cortex of the rat, overview. MeHg accumulates in the central nervous system (CNS) and preferentially accumulates in astrocytes, and it causes several neurotoxic effects, such as visual-field constriction, cerebellar ataxia and multimodal sensory disorders. MeHg-intoxicated animals display a significant decrease of NADPH-d neuropil reactivity across the visual cortex when compared to controls. The decreased neuropil reactivity to NADPH-d may also be related to MeHg-induced astrocytic dysfunction
-
N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide
-
calmodulin antagonist above 0.01 mM; i.e. W-7
N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(methoxycarbonyl)-piperazine-2-acetamide
inhibition of dimer formation in vivo and in vitro, efficiency is dependent on enzyme source
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
Ngamma-hydroxy-Ngamma-methyl-L-arginine
-
preincubation at 37°C leads to irreversible inactivation, substrates protect
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
PIN
-
human protein enzyme inhibitor, recombinantly expressed in Escherichia coli, the recombinant CREB-binding protein-bound inhibitor protein is purified by calmodulin affinity and inhibits the enzyme to a high extent at 0.001 mM
-
4-(3-amino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
IC50: 0.0119 mM
4-(3-amino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.0091 mM
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.004 mM
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
IC50: 0.01 mM
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.01 mM
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
-
IC50: 90 nM, pharmacokinetic profile
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
IC50: 60 nM, pharmacokinetic profile
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
-
IC50: 0.00056 mM, pharmacokinetic profile
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.0041 mM
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
IC50: 0.0012 mM
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
-
IC50: 0.008 mM
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
-
IC50: 0.00011mM
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
IC50: 0.00025mM
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
-
IC50: 0.00053mM
7-nitroindazole
-
reversible inhibition of endothelial enzyme, competitive versus tetrahydrobiopterin, no inhibition of cytochrome c reduction
7-nitroindazole
-
inhibits the neuronal NOS in vivo and reduces L-DOPA-induced dyskinesias in a rat model of parkinsonism. The rats show a lack of tolerance for the anti-dyskinetic effects
Ca2+
-
preincubation at 37°C leads to time-dependent inhibition of the enzyme
cyanide
-
heme-blocker inhibits superoxide formation after pretreatment of the enzyme
diphenylene iodonium
-
inhibition of superoxide production of recombinant isoform III
diphenylene iodonium
-
competitive, irreversible, complete, time and temperature dependent inhibition
ethylene glycol bis(beta-amino-ethylether)-N,N,N',N'-tetraacetic acid
-
i.e. EGTA, complete inhibition of cytosolic enzyme, partial inhibition of particulate enzyme
ethylene glycol bis(beta-amino-ethylether)-N,N,N',N'-tetraacetic acid
-
i.e. EGTA, complete inhibition of cytosolic enzyme, partial inhibition of particulate enzyme
ethylene glycol bis(beta-amino-ethylether)-N,N,N',N'-tetraacetic acid
-
i.e. EGTA, complete inhibition of cytosolic enzyme, partial inhibition of particulate enzyme
imidazole
-
the enzyme forms a sixcoordinate low-spin complex with inhibitor imidazole, interaction analysis
imidazole
-
inhibition of the endothelial enzyme, competitive versus L-arginine, no inhibition of cytochrome c reduction
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
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-arginine
-
L-arginine strongly stimulates oxygen consumption of eNOS and inhibits that of nNOS
NG-Nitro-L-arginine
complete inhibition at 1 mM, non-selective NOS inhibitor; complete inhibition at 1 mM, non-selective NOS inhibitor
Ngamma-monomethyl-L-arginine
-
inhibits citrulline formation, not cytochrome c reduction
Ngamma-monomethyl-L-arginine
-
L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site; endothelial and neuronal isoforms: reversible inhibition
Ngamma-monomethyl-L-arginine
-
L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site; inducible isoform: after preincubation irreversible, time- and concentration-dependent inactivation, without preincubation reversible inhibition
Ngamma-monomethyl-L-arginine
-
L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site; endothelial and neuronal isoforms: reversible inhibition; in presence of tetrahydrobiopterin 0.004 mM the neuronal isoform is inactivated
Ngamma-nitro-L-arginine
-
inhibits citrulline formation, not cytochrome c reduction
Ngamma-nitro-L-arginine
-
L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site; irreversible inactivation of neuronal and endothelial isoform after preincubation, unaffected by tetrahydrobiopterin
Ngamma-nitro-L-arginine
-
L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site; reversible inhibitor of inducible isoform from macrophage
Ngamma-nitro-L-arginine
-
L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site; irreversible inactivation of neuronal and endothelial isoform after preincubation, unaffected by tetrahydrobiopterin
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
Ngamma-nitro-L-arginine methyl ester
-
very slightly, only L-isomer and in presence of tetrahydrobiopterin and NADPH
Ngamma-nitro-L-arginine methyl ester
-
nearly complete inhibition at 0.5 mM
nitroblue tetrazolium
-
potent non-competitive inhibitor, partially reversible by tetrahydrobiopterin
Nomega-nitro-L-arginine methylester
L-NAME, the NOS inhibitor targets the oxygenase domain of the enzyme
additional information
-
not inhibitory: N-nitro-D-arginine methyl ester at 0.5 mM
-
additional information
a protein-based system is developed in which ligand inhibition can be rapidly evaluated in vitro
-
additional information
-
Ngamma,Ngamma'-dimethyl-L-arginine has no inhibitory effect
-
additional information
-
no inhibition by 4-(3-amino-propoxy)-6-chloro-1H-quinolin-2-one trifluoroacetic acid salt
-
additional information
interleukin-1 induces the degradation of isozyme iNOS, iNOS protein levels in osteoarthritic chondrocytes decreases to 45.4% of the control upon treatment with interleukin-1 for 15 min, and are further reduced to 41.5% when the treatment period is extended to 2 h; tissue necrosis factor-alpha induces nNOS disappearance, interleukin-1 induces the degradation of nNOS
-
additional information
interleukin-1 induces the degradation of isozyme iNOS, iNOS protein levels in osteoarthritic chondrocytes decreases to 45.4% of the control upon treatment with interleukin-1 for 15 min, and are further reduced to 41.5% when the treatment period is extended to 2 h; tissue necrosis factor-alpha induces nNOS disappearance, interleukin-1 induces the degradation of nNOS
-
additional information
-
interleukin-1 induces the degradation of isozyme iNOS, iNOS protein levels in osteoarthritic chondrocytes decreases to 45.4% of the control upon treatment with interleukin-1 for 15 min, and are further reduced to 41.5% when the treatment period is extended to 2 h; tissue necrosis factor-alpha induces nNOS disappearance, interleukin-1 induces the degradation of nNOS
-
additional information
-
fibroblast growth factor-2 treatment up-regulates the enzyme in tectume, but down-regulates it in the optic nerve, overview
-
additional information
-
the macrophage enzyme is not inhibited by calmodulin antagonists (N-4-aminobutyl-), (N-6-aminohexyl)-5-chloro-2-naphthalene sulfonamide
-
additional information
-
not inhibitory: N-nitro-L-arginine methyl ester, or specific inhibitor of inducible NOS, 1400W
-
additional information
inhibitory activity for coumarin derivatives, inhibitor screening, overview
-
additional information
-
inhibitory activity for coumarin derivatives, inhibitor screening, overview
-
additional information
-
inhibition of PSD-95/nNOS interaction by the nNOSalpha beta-finger antibody
-
additional information
-
although H4B binding seems unable to affect iNOSoxy capacity to activate peroxynitrite decomposition, the binding of Arg and citrulline at the distal side of the heme pocket drastically reduces peroxynitrite activation
-
additional information
there is decreased eNOS activity in tight-skin 1-mouse skin tissue
-
additional information
-
there is decreased eNOS activity in tight-skin 1-mouse skin tissue
-
additional information
-
no inhibitor of NADPH-diaphorase activity: methotrexate
-
additional information
-
the macrophage enzyme is not inhibited by calmodulin antagonists (N-4-aminobutyl-), (N-6-aminohexyl)-5-chloro-2-naphthalene sulfonamide; the macrophage enzyme is not inhibited by calmodulin antagonists (N-6-aminohexyl)-1-naphthalene sulfonamide
-
additional information
-
the macrophage enzyme is not inhibited by calmodulin antagonists (N-4-aminobutyl-), (N-6-aminohexyl)-5-chloro-2-naphthalene sulfonamide; the macrophage enzyme is not inhibited by calmodulin antagonists (N-6-aminohexyl)-1-naphthalene sulfonamide
-
additional information
-
no inhibition by 4-(3-amino-propoxy)-6-chloro-1H-quinolin-2-one trifluoroacetic acid salt and thiocoumarin
-
additional information
-
ethanol intake reduces eNOS and increases iNOS protein levels, while mRNA levels remain unaffected in female rat aorta
-
additional information
-
inhibition of PSD-95/nNOS interaction by the nNOSalpha beta-finger antibody
-
additional information
anthrax lethal factor potentially cleaves the regions (L191-Q192 and D264-N265) close to the NH2-terminus of neuronal nitric oxide synthase; inducible nitric oxide synthase is resistant to anthrax lethal factor-mediated cleavage
-
additional information
anthrax lethal factor potentially cleaves the regions (L191-Q192 and D264-N265) close to the NH2-terminus of neuronal nitric oxide synthase; inducible nitric oxide synthase is resistant to anthrax lethal factor-mediated cleavage
-
additional information
paraformaldehyde fixation of rat brain abolishes NOS activity in particulate and cytosolic fractions
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(6R,S)-Methyl-tetrahydropterin
-
activation in the absence of biopterin, not as effective as tetrahydrobiopterin
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
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
-
L-arginine
-
L-arginine strongly stimulates oxygen consumption of eNOS and inhibits that of nNOS, nonhydrolyzable L-arginine analogues are not stimulatory
thyroxin
0.001 mg thyroxin significantly increases nNOS activity and nNOS protein level to 153% compared to control
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
-
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
-
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
-
Calmodulin
-
substrate 2,6-dichlorophenolindophenol, about 10fold increase in activity in presence of calmodulin
Calmodulin
-
activates the neuronal NOS by binding and inhibiting the suppression through the C-terminal tail of the enzyme, overview
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
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
additional information
iNOS is induced by pathogens and their components, e.g. induction in alveolar macropages by infection with the intracellular pathogen Mycobacterium bovis
-
additional information
-
iNOS is induced by pathogens and their components, e.g. induction in alveolar macropages by infection with the intracellular pathogen Mycobacterium bovis
-
additional information
-
neopterin derivatives are completely inactive and do not bind to the enzyme
-
additional information
-
neopterin derivatives are completely inactive and do not bind to the enzyme
-
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
-
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
-
additional information
-
fibroblast growth factor-2 teratment up-regulates the enzyme in tectume, but down-regultes it in the optic nerve, overview
-
additional information
hepatic isozyme iNOS expression is induced in chronic liver cirrhosis early stages
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
rapid kinetic analysis, stopped-flow measurements under high pressure
-
additional information
additional information
-
rapid kinetic analysis, stopped-flow measurements under high pressure
-
additional information
additional information
-
biochemical pathway model, kinetic modeling, isozymes NOS1 and NOS3
-
additional information
additional information
-
kinetics of cytcochrome c reduction and of reaction with FMN and cytochrome c, overview, eNOS and nNOS differ slightly in their NADP(H) interaction and flavin thermodynamics, and show distinct electron transfer activities, two-state conformational equilibrium of the FMN subdomain, overview
-
additional information
additional information
kinetics, rapid-freeze method, overview
-
additional information
additional information
-
kinetics modeling and single-turnover reactions, kinetics of heme transitions during Arg oxidation, product stoichiometry analysis, detailed overview
-
additional information
additional information
-
kinetics of flavin reduction of the recombinant enzyme, overview
-
additional information
additional information
-
kinetics and kinetic modelling, stopped-flow measurements
-
additional information
additional information
-
kinetics and kinetic modelling, stopped-flow measurements
-
additional information
additional information
-
kinetics of NO and substrate binding, recombinant enzyme
-
additional information
additional information
-
kinetics of NO and substrate binding, recombinant enzyme
-
additional information
additional information
-
kinetics of heme-NO complex formation in the stopped-flow reaction
-
additional information
additional information
-
kinetic analysis of the interaction between peroxynitrite and the oxygenase domain of inducible NOS at three different pH values, overview
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.28
NADPH
DELTAG810 mutant enzyme, in the presence of 10 units/ml catalase and superoxide dismutase, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
0.32
NADPH
DELTAG810 mutant enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
2.33
NADPH
wild type enzyme, in the presence of 10 units/ml catalase and superoxide dismutase, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
2.57
NADPH
wild type enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
0.033
nitric oxide
DELTAG810 mutant enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
0.055
nitric oxide
DELTAG810 mutant enzyme, in the presence of 10 units/ml catalase and superoxide dismutase, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
0.92
nitric oxide
wild type enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
1.23
nitric oxide
wild type enzyme, in the presence of 10 units/ml catalase and superoxide dismutase, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0094 - 0.3666
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
0.0000022
N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(methoxycarbonyl)-piperazine-2-acetamide
-
0.000085 - 0.0852
N1-[cis-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(4'-chlorobenzyl)ethane-1,2-diamine
0.000388 - 0.4167
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
0.00025 - 0.0952
N1-[trans-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(3'-chlorobenzyl)ethane-1,2-diamine
0.00015
(4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N''-nitroguanidine
wild type nNOS
0.08
(4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N''-nitroguanidine
wild type eNOS
0.0094
3-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-ylamino]propan-1-ol
wild type nNOS
0.0492
3-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-ylamino]propan-1-ol
mutant nNOS D597N/M336V
0.3666
3-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-ylamino]propan-1-ol
wild type eNOS
0.0001
L-Nomega-nitroarginine-(4R)-amino-L-proline amide
wild type nNOS
0.11
L-Nomega-nitroarginine-(4R)-amino-L-proline amide
wild type eNOS
0.0003
L-Nomega-nitroarginine-2,4-L-diaminobutyramide
wild type nNOS
0.107
L-Nomega-nitroarginine-2,4-L-diaminobutyramide
wild type eNOS
0.000085
N1-[cis-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(4'-chlorobenzyl)ethane-1,2-diamine
wild type nNOS
0.0012
N1-[cis-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(4'-chlorobenzyl)ethane-1,2-diamine
mutant nNOS D597N/M336V
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
0.000388
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
wild type nNOS
0.0367
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
mutant nNOS D597N/M336V
0.4167
N1-[cis-4'-[(6''-aminopyridin-2''-yl)methyl]pyrrolidin-3'-yl]ethane-1,2-diamine
wild type eNOS
0.00025
N1-[trans-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(3'-chlorobenzyl)ethane-1,2-diamine
wild type nNOS
0.0061
N1-[trans-4'-[(6''-amino-4''-methylpyridin-2''-yl)methyl]pyrrolidin-3'-yl]-N2-(3'-chlorobenzyl)ethane-1,2-diamine
mutant nNOS D597N/M336V
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
0.002
Ngamma-monomethyl-L-arginine
-
neuronal isoform in presence of 0.004 mM tetrahydrobiopterin
0.0026
Ngamma-monomethyl-L-arginine
-
inducible isoform from macrophage after preincubation
0.0039
Ngamma-monomethyl-L-arginine
-
inducible isoform from macrophage without preincubation
0.00002
Ngamma-nitro-L-arginine
-
irreversible inactivation of endothelial isoform after preincubation
0.00009
Ngamma-nitro-L-arginine
-
irreversible inactivation of neuronal isoform after preincubation
0.0081
Ngamma-nitro-L-arginine
-
reversible inhibition of inducible macrophage isoform
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00041
4-(3-amino-propoxy)-6-chloro-1H-quinolin-2-one trifluoroacetic acid salt
Mus musculus
IC50: 410 nM, pharmacokinetic profile
0.00006 - 0.00056
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
0.0012 - 0.008
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
0.00011 - 0.00053
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
0.0076
4-(3-amino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Homo sapiens
-
IC50: 0.0076 mM
0.0091
4-(3-amino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Rattus norvegicus
-
IC50: 0.0091 mM
0.0119
4-(3-amino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Mus musculus
IC50: 0.0119 mM
0.004
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Homo sapiens
-
IC50: 0.004 mM
0.01
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Mus musculus
IC50: 0.01 mM
0.01
4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Rattus norvegicus
-
IC50: 0.01 mM
0.00006
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Mus musculus
IC50: 60 nM, pharmacokinetic profile
0.00009
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Homo sapiens
-
IC50: 90 nM, pharmacokinetic profile
0.00056
6-chloro-4-(3-aminopropoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Rattus norvegicus
-
IC50: 0.00056 mM, pharmacokinetic profile
0.0012
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Mus musculus
IC50: 0.0012 mM
0.0041
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Homo sapiens
-
IC50: 0.0041 mM
0.008
6-chloro-4-(3-dimethylamino-propoxy)-1-benzopyran-2-one hydrochloric acid salt
Rattus norvegicus
-
IC50: 0.008 mM
0.00011
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Homo sapiens
-
IC50: 0.00011mM
0.00025
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Mus musculus
IC50: 0.00025mM
0.00053
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Rattus norvegicus
-
IC50: 0.00053mM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.031
0.12
0.17
0.34 - 0.35
0.815
-
purified recombinant enzyme, H2O2-supported reduction of Ngamma-hydroxy-L-arginine, with tetrahydrobiopterin, 25°C
0.94 - 0.96
additional information
0.031
-
purified recombinant enzyme, NADPH/O2-supported reduction of Ngamma-hydroxy-L-arginine, tetrahydrobiopterin-free, 25°C
0.12
-
purified recombinant enzyme, H2O2-supported reduction of Ngamma-hydroxy-L-arginine, tetrahydrobiopterin-free, 25°C
0.17
-
purified recombinant enzyme, NADPH/O2-supported reduction of Ngamma-hydroxy-L-arginine, with tetrahydrobiopterin, 25°C
0.34 - 0.35
-
purified enzyme, recombinant, determined as NADPH-oxidase activity
additional information
-
enzyme activities with different flavodoxins, overview
additional information
-
low eNOS activity might involve an altered interaction with NADP(H)
additional information
-
iNOS activities in wild-type and chimeric mice, both with induced colitis, overview
additional information
-
activity in lung and liver only after induction by endotoxin
additional information
-
activity in hypertensive and healthy rats, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
7.4
7.5
7.6
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10
22
25
30
37
37
-
assay at
37
-
assay at
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
shelf fungus, collected from forest in Darjeeling, East Sikkim, India
-
-
brenda
collected in the intertidal zone of the Ria Formosa in Faro (Portugal)
-
-
brenda
hybrid tilapia, three isozymes eNOS, iNOS and nNOS
-
-
brenda
3 isoforms exist in bovine aortic endothelial cells differentiated by substrate specificity and Ca2+-dependence
-
-
brenda
-
440194, 440205, 440215, 440216, 440218, 440226, 440233, 440236, 660371, 660662, 660685, 671728, 672524, 673002, 673680, 674451, 684277
-
-
brenda
neuronal enzyme, full-length enzyme, FAD-FMN-domain, FAD-NADPH-domain
-
-
brenda
-
440192, 440193, 440195, 440198, 440201, 440209, 440217, 440222, 440225, 440226, 440234, 440236, 440239
-
-
brenda
3 isoforms exist in mouse macrophages differentiated by substrate specificity and Ca2+-dependence
-
-
brenda
-
440191, 440192, 440198, 440207, 440208, 440210, 440212, 440213, 440220, 440226, 658119, 659257, 659330
-
-
brenda
-
UniProt
brenda
different splice isoforms of nNOS, e.g. splicing variant nNOSalpha
-
-
brenda
Wistar and Wistar-Kyoto rats, and 1 month-old, prehypertensive/spontaneously hypertensive rats
-
-
brenda
Sprague-Dawley
-
-
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
main nervous structures (buccal nerve and nerve plate) in the bud of the tentacle
brenda
-
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
brenda
-
mainly in the lateral soma rind, surrounding the sensory glomeruli, partially in association with the antennal mechanosensory and motor neuropil
brenda
-
NADPH-diaphorase activity is found in the midpiece of the spermatozoa tail and epithelial cells of all intratesticular and excurrent ducts analyzed, except for nonciliated cells of the efferent ductules. Immunostaining shows cell-specific localization in the efferent ductules and region- and cell-specific localization in the epididymal duct
brenda
highest expression in hemocytes, followed by the tissues of hepatopancreas, brain and intestine. Relatively low transcriptional levels are detected in the tissues of eyestalk, gill, heart and muscle
brenda
-
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
brenda
-
NADPH-diaphorase is found in large and small neurons in the sensory, autonomic, and motor nuclei. In contrast to NADPH-diaphorase, nitric oxide synthase in the corresponding nuclei is always present in smaller quantities of mainly smaller neurons. In some nuclei (the nucleus ambiguus, the nucleus of the hypoglossal nerve) containing large numbers of NADPH-diaphorase-positive neurons, nitric oxide synthase immunoreactive cells are particularly rare
brenda
-
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
brenda
-
three isoforms of nitric oxide synthase are mainly localized in the uterine luminal and glandular epithelium and myometrium, and the intensity of immunostaining for inducible nitric oxide synthase and endothelial nitric oxide synthase increases gradually with temporal development of the postnatal uterus. The total nitric oxide synthase and inducible nitric oxide synthase activities are significantly increased at postnatal days 21 and 35. Although constitutive nitric oxide synthase activity is increased at postnatal day 21, it decreases subsequently at postnatal day 35. Inducible nitric oxide synthase protein expression is significantly increased at postnatal days 21 and 35
brenda
-
type I neurons are generated during early corticogenesis, whereas type II cells are produced over a wide prenatal time window persisting until birth. Type II nitrinergic neurons may undergo a period of development/differentiation, for over 1 month, before being NADPH-diaphorase reactive
brenda
constitutive expression of Ca22+/calmodulin-dependent neuronal nitric oxide synthase in the central and peripheral nervous system
brenda
-
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
brenda
n the skin, eNOS is present in the epidermal layer, hair follicles and also in the endothelial cells lining the blood vessels
brenda
-
distribution, overview, before and after axotomy and fibroblast growth factor-2 application
brenda
-
three isoforms of nitric oxide synthase are mainly localized in the uterine luminal and glandular epithelium and myometrium, and the intensity of immunostaining for inducible nitric oxide synthase and endothelial nitric oxide synthase increases gradually with temporal development of the postnatal uterus. The total nitric oxide synthase and inducible nitric oxide synthase activities are significantly increased at postnatal days 21 and 35. Although constitutive nitric oxide synthase activity is increased at postnatal day 21, it decreases subsequently at postnatal day 35. Inducible nitric oxide synthase protein expression is significantly increased at postnatal days 21 and 35
brenda
additional information
-
Pseudomonas aeruginosa stimulates expression of inducible nitric oxide synthase by A-549 cells
brenda
-
-
440190, 440191, 440192, 440196, 440197, 440198, 440203, 440210, 440212, 440213, 440220, 440228, 440232, 440236
brenda
-
from rats with unilateral depletion of dopamine in the substantia nigra compacta treated with L-DOPA at 30 mg/kg body weight for 34 days, nNOS expression is restricted to neurons
brenda
visual cortex, use of the NADPH-d histochemistry technique to evaluate the expression of NOS across the nervous system
brenda
-
from rats with unilateral depletion of dopamine in the substantia nigra compacta treated with L-DOPA at 30 mg/kg body weight for 34 days, nNOS expression is restricted to neurons
-
brenda
-
visual cortex, use of the NADPH-d histochemistry technique to evaluate the expression of NOS across the nervous system
-
brenda
-
cerebrum shows higher activity than cerebellum
-
brenda
-
the localization of NADPH-diaphorase and NO synthase is identical in the snail nervous system
brenda
the localization of NADPH-diaphorase and NO synthase is identical in the snail nervous system
brenda
-
-
brenda
iNOS is more frequently expressed in osteoarthritic than in normal chondrocytes, iNOS expression and activity in osteoarthritic chondrocytes is sub-maximal
brenda
nNOS is more frequently expressed in normal than in osteoarthritic chondrocytes
brenda
dental papilla cells (DPCs) are mesenchymal cells that are surrounded by the enamel organ during tooth development
brenda
-
dental papilla cells (DPCs) are mesenchymal cells that are surrounded by the enamel organ during tooth development
-
brenda
-
vascular, constitutive expression of the endothelial isozyme in endothelial cells
brenda
-
eNOS, endothelial cells of blood vessels
brenda
-
estradiol regulates the nitrergic system in the supraoptic and paraventricular hypothalamic nuclei under acute osmotic stress conditions, but the effects specifically depend on the anatomical subregions and different estrogen receptors
brenda
neurons of several nuclei of the hypothalamus, such as the arcuate nucleus (ARC) and paraventricular nucleus (PVN)
brenda
-
neurons of several nuclei of the hypothalamus, such as the arcuate nucleus (ARC) and paraventricular nucleus (PVN)
-
brenda
temporal expression of hepatic iNOS in liver cirrhosis, induced in rats by chronic bile duct ligation, overview
brenda
iNOS is the predominant isozyme in macrophages
brenda
-
strong histohemical labelling in sensory fibre branches of segmental nerves and in each of the sensory longitudinal axon bundles of ventral nerve cord ganglia. NADPH-diaphorase positive central sensory cells can be identified from among which the putative tactile receptors are characterized by constant, strong staining
brenda
-
strong histohemical labelling in sensory fibre branches of segmental nerves and in each of the sensory longitudinal axon bundles of ventral nerve cord ganglia. NADPH-diaphorase positive central sensory cells can be identified from among which the putative tactile receptors are characterized by constant, strong staining
brenda
-
central nervous system, natural variant with 105-amino acid deletion in the heme-binding domain
brenda
neurons of several nuclei of the hypothalamus, such as the arcuate nucleus (ARC) and paraventricular nucleus (PVN)
brenda
nitrergic neurons in the rat stomach, the myenteric cell bodies have single axons, type I morphology and a wide range of sizes. Nitrergic terminals do not provide baskets of terminals around myenteric neurons. The nitrergic neuron populations in the stomach supply the muscle layers and intramural arteries, but, unlike in the intestine, gastric interneurons do not express nNOS
brenda
the NADPH-d histochemistry stains a selective population of neurons in the brain. The staining allows the visualization of the dendritic tree, resembling a Golgi impregnation, and the cells are distributed sparsely in the cortical tissue, allowing their unbiased identification and reconstruction, quantitative analysis, overview
brenda
-
nitrergic neurons in the rat stomach, the myenteric cell bodies have single axons, type I morphology and a wide range of sizes. Nitrergic terminals do not provide baskets of terminals around myenteric neurons. The nitrergic neuron populations in the stomach supply the muscle layers and intramural arteries, but, unlike in the intestine, gastric interneurons do not express nNOS
-
brenda
-
neurons of several nuclei of the hypothalamus, such as the arcuate nucleus (ARC) and paraventricular nucleus (PVN)
-
brenda
-
the NADPH-d histochemistry stains a selective population of neurons in the brain. The staining allows the visualization of the dendritic tree, resembling a Golgi impregnation, and the cells are distributed sparsely in the cortical tissue, allowing their unbiased identification and reconstruction, quantitative analysis, overview
-
brenda
from rats at different ages. Odontoblasts are strongly stained for NADPH-d. The staining intensity of odontoblasts near the future cusp and root is higher than that of other locations of the first molar. Odontoblasts in the first molar from 3-month-old rats are also positive for NADPH-d staining. Odontoblasts in the first molar from 8-month-old rats are weakly positive for NADPH-d staining. Semiquantitative evaluation results of NADPH-d staining suggests that NOS may be involved in the differentiation and function of odontoblasts
brenda
-
from rats at different ages. Odontoblasts are strongly stained for NADPH-d. The staining intensity of odontoblasts near the future cusp and root is higher than that of other locations of the first molar. Odontoblasts in the first molar from 3-month-old rats are also positive for NADPH-d staining. Odontoblasts in the first molar from 8-month-old rats are weakly positive for NADPH-d staining. Semiquantitative evaluation results of NADPH-d staining suggests that NOS may be involved in the differentiation and function of odontoblasts
-
brenda
-
distribution, overview, in retinorecipient tectal layer, before and after axotomy and fibroblast growth factor-2 application
brenda
-
nNOS, nerve cell bodies and neuronal fibers
brenda
nitrergic neurons in the rat stomach comprising similar proportions of myenteric neurons, about 30%, in all gastric regions, e.g. the longitudinal, circular and oblique layers of the external muscle, the muscularis mucosae and arteries within the gastric wall
brenda
-
nitrergic neurons in the rat stomach comprising similar proportions of myenteric neurons, about 30%, in all gastric regions, e.g. the longitudinal, circular and oblique layers of the external muscle, the muscularis mucosae and arteries within the gastric wall
-
brenda
-
main nervous structures (buccal nerve and nerve plate) in the bud of the tentacle
brenda
-
NADPH-diaphorase activity is found in the midpiece of the spermatozoa tail and epithelial cells of all intratesticular and excurrent ducts analyzed, except for nonciliated cells of the efferent ductules. Immunostaining shows cell-specific localization in the efferent ductules and region- and cell-specific localization in the epididymal duct
brenda
eNOS immunoreactivity is detected in germ cells, Sertoli cells, Leydig cells and vascular endothelial cells of the testis
brenda
iNOS positive cells are detected in seminiferous epithelial cells, especially in germ cells of the testis
brenda
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
brenda
additional information
-
localization and distribution of nitric oxide synthase and other neuronal markers in the podia of Holothuria arguinensis, detailed overview. The podia terminal end is the most specialized area and is characterized by a specific nervous arrangement, consisting of a distinct nerve plate, rich in cells and fibers containing potential sensory cells staining positively for neuronal markers. In sea cucumbers, cells with morphological characteristics typical of sensory cells have been described in the tentacles, tube feet, and papillae. NADPH-diaphorase histochemistry and NOS immunohistochemistry. The NADPH-diaphorase staining and the anti-NOS antibody show an overall similar distribution in the tentacle. In the stem, the longitudinal buccal nerve and the buccal nerve are strongly reactive to both markers. The mesothelium is also positive for NADPH-d and anti-NOS. In the bud, the two methods reveal that NOS is present in both the buccal nerve and mesothelium
brenda
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
brenda
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
brenda
additional information
-
3 distinct isoforms: 1. a membrane-associated, constitutive enzyme from tha vascular endothelium, 2. a soluble, constitutive enzyme from neuronal cells, 3. an endotoxin- and cytokine-inducible enzyme exemplified by that from murine macrophages
brenda
additional information
-
activity of constitutive enzymes is regulated by binding of calmodulin and Ca2+, the inducible enzyme is regulated by binding of calmodulin, not by Ca2+
brenda
additional information
-
nNOS splicing variants tissue distribution, immunohistochemic analysis, overview
brenda
additional information
-
no activity in gill, intestine, and liver
brenda
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
brenda
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
brenda
additional information
expression analysis in isolated hepatocytes, healthy liver, and cirrhotic liver, overview
brenda
additional information
-
nNOS splicing variants tissue distribution, immunohistochemic analysis, overview
brenda
additional information
distribution of NADPH-d-positive neurons and fibers in the paraventricular nucleus (PVN) after saline and leptin treatment, in situ overview
brenda
additional information
-
distribution of NADPH-d-positive neurons and fibers in the paraventricular nucleus (PVN) after saline and leptin treatment, in situ overview
brenda
additional information
immunohistochemic enzyme and NADPH histochemic analysis, distributions of nNOS neurons and their terminals throughout the rat stomach, overview. NADPH diaphorase is the colour reaction that reveals the presence of NADPH oxidases, and because nNOS is a NADPH oxidase, it is revealed by NADPHd histochemistry
brenda
additional information
NO synthase (NOS) immunohistochemic analysis and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining in vivo in rat odontoblasts. The expression of neuronal NOS and endothelial NOS is upregulated during the odontoblastic differentiation of DPCs
brenda
additional information
pattern of NADPH-d neuropil staining and pattern of astrocyte reactivity, qualitative and quantitative analysis, overview. MeHg-intoxicated animals display a significant decrease of NADPH-d neuropil reactivity across the visual cortex when compared to controls
brenda
additional information
determination of NADPH diaphorase staining in preganglionic terminals, staining generally ascribed to NADH diaphorase activity in aldehyde-treated tissues
brenda
additional information
-
NO synthase (NOS) immunohistochemic analysis and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) staining in vivo in rat odontoblasts. The expression of neuronal NOS and endothelial NOS is upregulated during the odontoblastic differentiation of DPCs
-
brenda
additional information
-
immunohistochemic enzyme and NADPH histochemic analysis, distributions of nNOS neurons and their terminals throughout the rat stomach, overview. NADPH diaphorase is the colour reaction that reveals the presence of NADPH oxidases, and because nNOS is a NADPH oxidase, it is revealed by NADPHd histochemistry
-
brenda
additional information
-
determination of NADPH diaphorase staining in preganglionic terminals, staining generally ascribed to NADH diaphorase activity in aldehyde-treated tissues
-
brenda
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
-
brenda
additional information
-
pattern of NADPH-d neuropil staining and pattern of astrocyte reactivity, qualitative and quantitative analysis, overview. MeHg-intoxicated animals display a significant decrease of NADPH-d neuropil reactivity across the visual cortex when compared to controls
-
brenda
additional information
no expression in salivary glands and the gland of Leiblein
brenda
additional information
-
no expression in salivary glands and the gland of Leiblein
brenda
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
brenda
additional information
-
immunohistochemic analysis of enzyme distribution, overview
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
NADPH-diaphorase reactive/NO synthase -immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
NADPH-diaphorase reactive/NO synthase -immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
-
-
brenda
-
NADPH-diaphorase reactive/NO synthase -immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
NADPH-diaphorase reactive/NO synthase -immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
iNOS contains several characteristic endoplasmic reticulum (ER)-localization sequences. iNOS is likely to be glycosylated in the endoplasmic reticulum
brenda
-
iNOS contains several characteristic endoplasmic reticulum (ER)-localization sequences. iNOS is likely to be glycosylated in the endoplasmic reticulum
-
brenda
-
constitutive endothelial enzyme: predominantly membrane-bound, inducible macrophage enzyme: equally distributed between cytosol and membrane, small constitutive membrane-bound portion in murine macrophages
brenda
-
NADPH-diaphorase reactive/NO synthase -immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
NADPH-diaphorase reactive/NO synthase -immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
-
constitutive endothelial enzyme: predominantly membrane-bound, inducible macrophage enzyme: equally distributed between cytosol and membrane, small constitutive membrane-bound portion in murine macrophages
brenda
total NOS activity is enriched in the intracellular membrane fraction at normal salt diet
brenda
-
distinct enzyme not identical to other known isoforms
brenda
-
isozyme NOS1 contains a mitochondrial targeting signal
brenda
-
NADPH-diaphorase reactive/NO synthase-immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
NADPH-diaphorase reactive/NO synthase -immunoreactive materials are localized on the nuclear envelope and membrane segments of the rough and smooth endoplasmic reticulum, as well as the cell membrane and axolemma of positive perikarya
brenda
-
NADPH-diaphorase reactive and NO synthase-immunoreactive varicosities connect to neighboring neurons with both unspecialized and specialized synaptic contacts
brenda
-
in the varicosities, the majority of the NADPH-d reactive/NOS-immunoreactive membrane segments are detected in round and pleomorph agranular vesicles of small size (50-200 nm)
brenda
NADPH-diaphorase reactive and NO synthase-immunoreactive varicosities connect to neighboring neurons with both unspecialized and specialized synaptic contacts
brenda
in the varicosities, the majority of the NADPH-d reactive/NOS-immunoreactive membrane segments are detected in round and pleomorph agranular vesicles of small size (50-200 nm)
brenda
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
-
brenda
additional information
-
no evidence for the postsynaptic location is found
-
brenda
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
-
brenda
additional information
-
no evidence for the postsynaptic location is found
-
brenda
additional information
no evidence for the postsynaptic location is found
-
brenda
additional information
-
3 distinct isoforms: 1. a membrane-associated, constitutive enzyme from the vascular endothelium, 2. a soluble, constitutive enzyme from neuronal cells, 3. an endotoxin- and cytokine-inducible enzyme exemplified by that from murine macrophages
-
brenda
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
-
brenda
additional information
-
activity of constitutive enzymes is regulated by binding of calmodulin and Ca2+, the inducible enzyme is regulated by binding of calmodulin, not by Ca2+
-
brenda
additional information
N-glycosylation of proteins starts in the endoplasmic reticulum, continues in the Golgi, and ends at the plasma membrane. As mentioned above, iNOS has characteristic ER localization sequences and locates in the Golgi and cell membrane. iNOS is located both in cytoplasm and on cell membrane, it is not only a cytoplasmic protein but also a membrane protein
-
brenda
additional information
-
N-glycosylation of proteins starts in the endoplasmic reticulum, continues in the Golgi, and ends at the plasma membrane. As mentioned above, iNOS has characteristic ER localization sequences and locates in the Golgi and cell membrane. iNOS is located both in cytoplasm and on cell membrane, it is not only a cytoplasmic protein but also a membrane protein
-
brenda
additional information
-
N-glycosylation of proteins starts in the endoplasmic reticulum, continues in the Golgi, and ends at the plasma membrane. As mentioned above, iNOS has characteristic ER localization sequences and locates in the Golgi and cell membrane. iNOS is located both in cytoplasm and on cell membrane, it is not only a cytoplasmic protein but also a membrane protein
-
-
brenda
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
-
brenda
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
-
brenda
additional information
-
subcellular distribution of NOS and caveolin-1, nNOS and iNOS are co-localized with caveolin-1, overview
-
brenda
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
-
-
brenda
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
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
additional information
malfunction
inhibition of NOS function by NOS inhibitor L-NG-monomethyl arginine (L-NMMA) results in reduced formation of mineralized nodules and expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP1) during dental papilla cell (DPC) differentiation
malfunction
attachment of N-glycan to the Asn695 residue inhibits activity by disturbing electron transfer. N-glycosylated iNOS consumes NADPH more slowly than the unliganded enzyme. Mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
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
malfunction
-
attachment of N-glycan to the Asn695 residue inhibits activity by disturbing electron transfer. N-glycosylated iNOS consumes NADPH more slowly than the unliganded enzyme. Mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
-
malfunction
-
inhibition of NOS function by NOS inhibitor L-NG-monomethyl arginine (L-NMMA) results in reduced formation of mineralized nodules and expression of dentin sialophosphoprotein (DSPP) and dentin matrix protein (DMP1) during dental papilla cell (DPC) differentiation
-
metabolism
-
activation of G protein-coupled estrogen receptor in the supraoptic and paraventricular nuclei of the hypothalamus inhibits the phosphorylation of ERK 1/2, which induces a decrease in NADPH-diaphorase expression
metabolism
the enzyme plays an important role in host defense system by catalyzing the production of nitric oxide
physiological function
-
the brain neuronal NOS and inducible NOS are respectively involved in the bombesin-induced secretion of noradrenaline and adrenaline from the adrenal medulla
physiological function
si-RNA mediated knockdown of eNOS leads to a striking increase in AMP-activated protein kinase phosphorylation, homozygot eNOS knockout mice show a marked increase in AMP-activated protein kinase phosphorylation in liver and lung compared to wild type mice
physiological function
eNOS selectively activates N-Ras but not K-Ras on the Golgi complex of T cells engaged with antigen-presenting cells by S-nitrosylation at Cys118
physiological function
-
developmental but not adult exposure to polychlorinated biphenyls significantly reduces NO synthase responses to hyperosmolality in neuroendocrine cells. Reduced NADPH diaphorase activity produced by in utero exposure persists in stimulated late adult rats concomitant with reduced osmoregulatory capacity
physiological function
-
during muscle pain development, a significant contralateral increase in the number of NADPH-diaphorase reactive cells is accompanied by anipsilateral increase in c-Fos expression in lamina VII. NADPH-diaphorase reactive neurons of the contralateral ventral horn may be involved through commissural connections in the maintenance of the neuronal activity associated with acute muscle inflammation. During acute myositis, plastic changes in the ventral horn may activate the processes of disinhibition due to an increase in the number of NADPH-diaphorase reactive neurons in the spinal gray matter
physiological function
-
estradiol regulates the nitrergic system in the supraoptic and paraventricular hypothalamic nuclei under acute osmotic stress conditions, but the effects specifically depend on the anatomical subregions and different estrogen receptors. The inhibition of estrogen receptor alpha enhances the effect of 1.5 M NaCl injection, inducing a further decrease in the number of NADPH-diaphorase-positive cells. The estrogen receptor beta agonist enhances and the estrogen receptor beta antagonist blocks the effect of NaCl injection on the number of NADPH-diaphorase-positive neurons in the supraoptic hypothalamic nuclei and in the medial magnocellular subdivision of the paraventricular hypothalamic nuclei
physiological function
-
the product nitric oxide may function as a co-transmitter in the central nervous system of Helix pomatia
physiological function
endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis
physiological function
NADPH oxidases (NOX2/NOX4) and inducible nitric oxide synthase (iNOS) derived oxidative stress play a key role in psoriasis induced kidney dysfunction. NADPH oxidase (NOX2 and NOX4) isoforms, and inducible nitric oxidase synthase (iNOS) are elevated in the renal tissue under inflammatory conditions such as acute kidney injury and chronic kidney disease. These enzymes are capable of producing reactive oxygen species (ROS) in large quantities under inflammatory conditions, which may cause oxidative damage to biological macromolecules such as lipids, proteins and nucleic acids leading to malfunction of cellular structures through dysregulation of ion pumps, and enzymatic activity
physiological function
nitric-oxide synthase (NOS) is required in mammals to generate nitric-oxide for regulating blood pressure, synaptic response, and immune defense
physiological function
the product nitric oxide may function as a co-transmitter in the central nervous system of Helix pomatia
physiological function
leptin-induced NO production in tanycytes may affect the neurogenesis occurs in the hypothalamus. The increased NADPH-d staining in both the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the leptin-treated rats suggests that both the PVN and ARC may be important centers in the hypothalamus for the leptin action, mediated at least in part by increased NO synthesis. The present observations also suggest that leptin may activate NOS thereby resulting in increased production of NO in hypothalamic tanycytes, possibly affecting the release of neurohormones and hypothalamic neurogenesis
physiological function
nitrergic neurons in the rat stomach supply the longitudinal, circular and oblique layers of the external muscle, the muscularis mucosae and arteries within the astric wall. A small number of fibres are in the mucosa. All the neurons appear to have a single axon and in most cases a type I morphology. Type I is the typical morphology of enteric motor neurons that supply the muscle of the gastrointestinal tract. Neuronal nitric oxide synthase (nNOS) neurons do not supply terminals around myenteric nerve cells, whether NADPHd histochemistry or nNOS immunohistochemistry is used to locate the terminals of nNOS neurons. Thus, nNOS appears to be exclusively in motor neurons supplying the muscle of the rat stomach. This may be different from other species. nNOS immunoreactivity identifies 4 classes of motor neurons that supply the muscle of the rat stomach, an analysis of cell body sizes does not identify separate grouping of neurons. The rat stomach harbours large numbers of nNOS neurons, all or almost all of which are motor neurons supplying the external muscle, the muscularis mucosae and intramural arteries
physiological function
nitric oxide (NO) regulates the functions of multiple cells and organ tissues, including stem cell differentiation and bone formation, role of nitric oxide in odontoblastic differentiation of rat dental papilla cells, overview. NO regulates the odontoblastic differentiation of dental papilla cells (DPCs), thereby influencing dentin formation and tooth development. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) promotes the viability of DPCs. Extracellular matrix mineralization and odontogenic markers expression are elevated by SNAP at low concentrations and suppressed at high concentration. Blocking the generation of cyclic guanosine monophosphate (cGMP) with 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) abolishes the positive influence of SNAP on the odontoblastic differentiation of DPCs
physiological function
nitric oxide (NO) is a ubiquitous gaseous cellular messenger with multiple physiological roles in the brain, such as synaptic plasticity, neurotransmission, neuronal communication, neurogenesis, learning, and memory. NO can be generated by three different isoforms of the enzyme nitric oxide synthase (NOS): neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), from L-arginine as the substrate and molecular oxygen and NADPH as cosubstrates
physiological function
inducible nitric oxide synthase (iNOS) is a key inflammatory factor. It functions in both acute and chronic inflammation. Nitric oxide (NO) is a signaling mediator with many diverse and often contradictory biological activities. In mammals, NO is produced by a family of nitric oxide synthase (NOS). The NOS family includes neuronal nitric oxide synthase (nNOS, type I), inducible nitric oxide synthase (iNOS, type II), and endothelial nitric oxide synthase (eNOS, type III). All these three NOS isoforms catalyze a similar reaction. Consuming NADPH and O2, NOS oxidizes L-arginine into L-citrulline and releases NO. The reaction is an oxidation-reduction reaction, and electron transfer plays a vital role. Inducible nitric oxide synthase (iNOS) plays critical roles in the inflammatory response and host defense. The essence of nitric oxide synthase catalytic reaction is an electron transfer process, which involves a series of conformational changes, and the linker between the flavin mononucleotide-binding domain and the flavin adenine dinucleotide-binding domain plays vital roles in the conformational changes. Residue Asn695 is part of the linker. Enzyme iNOS is N-glycosylated at its Asn695 residue and N-glycosylation of Asn695 might suppress iNOS activity by disturbing electron transfer
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
physiological function
-
nitric oxide (NO) is synthesized from L-arginine by the NADPH-dependent enzyme nitric oxide synthase (NOS), and is involved in many essential biological functions including immune defense, vascular regulation, muscle relaxation, and neuromodulation, and neurotransmission
physiological function
in endothelium and placenta, NO is biosynthesized by the endothelial nitric oxide synthase (eNOS), and confers to endothelium its vasorelaxing and anti-aggregant properties. NO participates to placentation and the synthesis of the vascular endothelial growth factor (VEGF). NO plays an essential role in vascular homeostasis due to its vasodilatory effect. NO is synthesized by nitric oxide synthases (NOS), from L-arginine and molecular oxygen (O2). In short, the reaction allowing NO synthesis can be compared to two monooxygenation reactions. The first reaction consists of the oxidation of L-arginine. This reaction produces an intermediate, -OH-L-arginine, which is rapidly oxidized into L-citrulline. These two oxygenation reactions occur in parallel with a concomitant conversion of NADPH to NADP+. The electrons are supplied by NADPH, transferred to flavins (FAD and FMN) and calmodulin, then presented to heme, the catalytic center. Three NOS isoforms have been characterized, the neuronal NOS (nNOS or NOS1), the inducible NOS (iNOS or NOS2) and the endothelial NOS (eNOS or NOS3). NO released by endothelial cells in vivo causes a permanent vasodilation of the arterial tone that helps to regulate arterial pressure. During pregnancy, NO has a primary role in vasodilation and blood pressure regulation, placentation and VEGF synthesis. Oxidative stress impact on NO bioavailability, detailed overview. S-Glutathionylation can be promoted by NO, via mechanisms implicating S-nitrosoglutathione (GSNO) and thiyl radicals. S-glutathionylated proteins reversibly accumulate under oxidative stress conditions and can be rapidly reduced by reducing agents and glutaredoxins. S-glutathionylation alters the structure, folding and function of proteins, and can be considered as an adaptative and protective mechanism against the irreversible oxidation of cysteine residues during oxidative stress
physiological function
-
inducible nitric oxide synthase (iNOS) is a key inflammatory factor. It functions in both acute and chronic inflammation. Nitric oxide (NO) is a signaling mediator with many diverse and often contradictory biological activities. In mammals, NO is produced by a family of nitric oxide synthase (NOS). The NOS family includes neuronal nitric oxide synthase (nNOS, type I), inducible nitric oxide synthase (iNOS, type II), and endothelial nitric oxide synthase (eNOS, type III). All these three NOS isoforms catalyze a similar reaction. Consuming NADPH and O2, NOS oxidizes L-arginine into L-citrulline and releases NO. The reaction is an oxidation-reduction reaction, and electron transfer plays a vital role. Inducible nitric oxide synthase (iNOS) plays critical roles in the inflammatory response and host defense. The essence of nitric oxide synthase catalytic reaction is an electron transfer process, which involves a series of conformational changes, and the linker between the flavin mononucleotide-binding domain and the flavin adenine dinucleotide-binding domain plays vital roles in the conformational changes. Residue Asn695 is part of the linker. Enzyme iNOS is N-glycosylated at its Asn695 residue and N-glycosylation of Asn695 might suppress iNOS activity by disturbing electron transfer
-
physiological function
-
leptin-induced NO production in tanycytes may affect the neurogenesis occurs in the hypothalamus. The increased NADPH-d staining in both the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the leptin-treated rats suggests that both the PVN and ARC may be important centers in the hypothalamus for the leptin action, mediated at least in part by increased NO synthesis. The present observations also suggest that leptin may activate NOS thereby resulting in increased production of NO in hypothalamic tanycytes, possibly affecting the release of neurohormones and hypothalamic neurogenesis
-
physiological function
-
nitric oxide (NO) is a ubiquitous gaseous cellular messenger with multiple physiological roles in the brain, such as synaptic plasticity, neurotransmission, neuronal communication, neurogenesis, learning, and memory. NO can be generated by three different isoforms of the enzyme nitric oxide synthase (NOS): neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), from L-arginine as the substrate and molecular oxygen and NADPH as cosubstrates
-
physiological function
-
nitrergic neurons in the rat stomach supply the longitudinal, circular and oblique layers of the external muscle, the muscularis mucosae and arteries within the astric wall. A small number of fibres are in the mucosa. All the neurons appear to have a single axon and in most cases a type I morphology. Type I is the typical morphology of enteric motor neurons that supply the muscle of the gastrointestinal tract. Neuronal nitric oxide synthase (nNOS) neurons do not supply terminals around myenteric nerve cells, whether NADPHd histochemistry or nNOS immunohistochemistry is used to locate the terminals of nNOS neurons. Thus, nNOS appears to be exclusively in motor neurons supplying the muscle of the rat stomach. This may be different from other species. nNOS immunoreactivity identifies 4 classes of motor neurons that supply the muscle of the rat stomach, an analysis of cell body sizes does not identify separate grouping of neurons. The rat stomach harbours large numbers of nNOS neurons, all or almost all of which are motor neurons supplying the external muscle, the muscularis mucosae and intramural arteries
-
physiological function
-
nitric oxide (NO) regulates the functions of multiple cells and organ tissues, including stem cell differentiation and bone formation, role of nitric oxide in odontoblastic differentiation of rat dental papilla cells, overview. NO regulates the odontoblastic differentiation of dental papilla cells (DPCs), thereby influencing dentin formation and tooth development. The NO donor S-nitroso-N-acetylpenicillamine (SNAP) promotes the viability of DPCs. Extracellular matrix mineralization and odontogenic markers expression are elevated by SNAP at low concentrations and suppressed at high concentration. Blocking the generation of cyclic guanosine monophosphate (cGMP) with 1H-(1,2,4)oxadiazolo-(4,3-a)quinoxalin-1-one (ODQ) abolishes the positive influence of SNAP on the odontoblastic differentiation of DPCs
-
additional information
the large numbers of nNOS neurons and the density of innervation of the circular muscle and pyloric sphincter suggest that there is a finely graded control of motor function in the stomach by the recruitment of different numbers of inhibitory motor neurons
additional information
residue Asn695 of the mouse iNOS locates at the hinge segment which connects the FMN-binding domain to the FAD-binding domain. The electrostatic and flexibility properties of hinge segment are critical for electron transfer from CPR to its redox partners. For mouse iNOS, N-glycosylation of Asn695 might disturb electron transfer by influencing the electrostatic and flexibility properties of the hinge segment
additional information
-
residue Asn695 of the mouse iNOS locates at the hinge segment which connects the FMN-binding domain to the FAD-binding domain. The electrostatic and flexibility properties of hinge segment are critical for electron transfer from CPR to its redox partners. For mouse iNOS, N-glycosylation of Asn695 might disturb electron transfer by influencing the electrostatic and flexibility properties of the hinge segment
additional information
-
residue Asn695 of the mouse iNOS locates at the hinge segment which connects the FMN-binding domain to the FAD-binding domain. The electrostatic and flexibility properties of hinge segment are critical for electron transfer from CPR to its redox partners. For mouse iNOS, N-glycosylation of Asn695 might disturb electron transfer by influencing the electrostatic and flexibility properties of the hinge segment
-
additional information
-
the large numbers of nNOS neurons and the density of innervation of the circular muscle and pyloric sphincter suggest that there is a finely graded control of motor function in the stomach by the recruitment of different numbers of inhibitory motor neurons
-
Show AA Sequence and Transmembrane Helices (5301 entries)
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Longer loading times are possible. Please use the AA Sequence and Transmembrane Helices Search for a specific query.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
120000
135000
150000
152000
160000
200000
300000
89000
-
2 * 89000, nNOS, SDS-PAGE, bands of 47 kDa and 29 kDa also occur
additional information
-
dissociates irreversibly into subunits in the absence of L-arginine, FAD and tetrahydrobiopterin
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
monomer
additional information
dimer
-
subunit disassembly and unfolding of the protein following a pH jump from 7.5 to 2.8
dimer
all three NOS isoforms are composed of an N-terminal catalytic oxygenase module (NOSox) and a C-terminal-electron-supplying reductase module (NOSred), and NOSox and NOSred are linked by a Ca2+/calmodulin binding region. NOSox contains a heme-binding site, a tetrahydrobiopterin-binding site and an arginine-binding site. NOSred contains an flavin mononucleotide-binding site, an flavin adenine dinucleotide-binding site and an NADPH-binding site. Only dimerized NOS has catalytic activity
dimer
-
all three NOS isoforms are composed of an N-terminal catalytic oxygenase module (NOSox) and a C-terminal-electron-supplying reductase module (NOSred), and NOSox and NOSred are linked by a Ca2+/calmodulin binding region. NOSox contains a heme-binding site, a tetrahydrobiopterin-binding site and an arginine-binding site. NOSred contains an flavin mononucleotide-binding site, an flavin adenine dinucleotide-binding site and an NADPH-binding site. Only dimerized NOS has catalytic activity
-
dimer
-
2 * 89000, nNOS, SDS-PAGE, bands of 47 kDa and 29 kDa also occur
homodimer
the enzyme is a large homodimer with a reductase and an oxygenase domains that coordinate a multistep, interdomain electron transfer mechanism to oxidize L-arginine and generate nitric oxide
additional information
-
bimodal enzyme, comprising of an N-terminal oxygenase domain that binds protoporphyrin IX /heme, 6R-tetrahydrobiopterin, and L-arginine, and a C-terminal reductase domain that binds FMN, FAD, and NADPH, the two domains are linked together by a calmodulin binding sequence
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
additional information
-
D-arginine inhibits reconstitution of dimer from subunits
additional information
-
dimer formation, each subunit consists of: 1 oxygenase domain containing heme, tetrahydrobiopterin, substrate binding site and 1 reductase domain containing FAD, FMN, calmodulin, NADPH binding site
additional information
-
dimer formation, each subunit consists of: 1 oxygenase domain containing heme, tetrahydrobiopterin, substrate binding site and 1 reductase domain containing FAD, FMN, calmodulin, NADPH binding site
additional information
-
dimer formation, each subunit consists of: 1 oxygenase domain containing heme, tetrahydrobiopterin, substrate binding site and 1 reductase domain containing FAD, FMN, calmodulin, NADPH binding site
additional information
-
dimeric structure is required for enzyme activity, interaction between subunits via oxygenase domains
additional information
-
dimeric structure is required for enzyme activity, interaction between subunits via oxygenase domains
additional information
-
significant amino acid sequence homology to NADPH-cytochrome P-450-type hemoprotein
additional information
-
significant amino acid sequence homology to NADPH-cytochrome P-450-type hemoprotein
additional information
-
nNOS reductase structure homology modeling, overview
additional information
-
the splicing variant nNOSaalpha contains a specific beta-finger motif involved in PDZ domain scaffolding
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
flavoprotein
glycoprotein
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
sumoylation
isoform neuronal nitric oxide synthase is clearly a SUMO-1 target protein both in vitro and at the cellular level. SUMO-1 conjugation of neuronal nitric oxide synthase depends on Ubc9 (E2). The interaction between neuronal nitric oxide synthase and Ubc9 is facilitated by PIASxbeta (E3) and SUMO-1 is deconjugated from neuronal nitric oxide synthase by SENP1 and SENP2
additional information
glycoprotein
iNOS is N-glycosylated in vitro and in vivo. Mass spectrometry studies identify Asn695 as an N-glycosylation site of murine iNOS, mapping of the iNOS N-glycosylation site. iNOS expressed by LPS- and IFN-gamma-stimulated Raw-264.7 cells can be recognized by concanavalin A (ConA). Glycosylation at Asn695 might suppress inducible nitric oxide synthase activity by disturbing electron transfer
glycoprotein
-
iNOS is N-glycosylated in vitro and in vivo. Mass spectrometry studies identify Asn695 as an N-glycosylation site of murine iNOS, mapping of the iNOS N-glycosylation site. iNOS expressed by LPS- and IFN-gamma-stimulated Raw-264.7 cells can be recognized by concanavalin A (ConA). Glycosylation at Asn695 might suppress inducible nitric oxide synthase activity by disturbing electron transfer
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
orthorhombic crystals from NOS oxygenase domain lacking the N-terminal 114 residues, preparation in presence of imidazole, structure analysis via x-ray diffraction, also with bound inhibitor N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(methoxycarbonyl)-piperazine-2-acetamide
x-ray crystal structure of the heme-binding domains of neuronal wild-type and mutant with deletion in the heme-binding domain
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
I224V
S1179D
S617D
the phosphomimetic substitution doubles the maximum calmodulin-dependent enzyme activity and decreases the EC50(Ca2+) values for calmodulin binding and enzyme activation compared to the wild type enzyme
S617D/S1179D
the mutation doubles maximal synthase activity, partially disinhibits cytochrome c reductase activity, and lowers the EC50(Ca2+) values for calmodulin binding and enzyme activation
S617D/S635D
the maximum calmodulin-dependent synthase activity of S617/635D eNOS is about 2fold higher than the wild type activity
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
C415A
-
contains no heme, no bound tetrahydrobiopterin, unable to oxidize NADPH and to synthezise nitric oxide, unaltered ability to reduce cytochrome c
C415H
-
contains nearly no heme, no bound tetrahydrobiopterin, unable to oxidize NADPH and to synthezise nitric oxide, unaltered ability to reduce cytochrome c
N695Q
site-directed mutagenesis, mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
W457A
increase in Km-value of tetrahydrobiopterin and L-arginine, decrease in NO synthesis activity, slower building of enzyme heme-NO complex and slower reactivity of heme-dioxy intermediate
N695Q
-
site-directed mutagenesis, mutating Asn695 to Gln695 yields an iNOS that exhibits greater enzyme activity compared to wild-type. NO produced by N695Q iNOS-transformed HEK293 cells is 1.32fold greater than that of N-glycosylated iNOS, the increased enzyme activity of N695Q iNOS in HEK293 cells was caused by loss of N-glycan
-
D1393E
-
normal composition, spectral properties and binding of cofactors, substrates and calmodulin, slower NADPH-dependent cytochrome c and ferricyanide reductase activity
D1393N
-
normal composition, spectral properties and binding of cofactors, substrates and calmodulin, slower NADPH-dependent cytochrome c and ferricyanide reductase activity
D1393V
-
normal composition, spectral properties and binding of cofactors, substrates and calmodulin, slower NADPH-dependent cytochrome c and ferricyanide reductase activity
DELTAG810
-
deletion changes redox behaviour of mutant. In the early stage of flavin reduction, similar to the case of wild-type, the hydroquinone FADH2-FMN quickly converts to the disemiquinone and does not accumulate. Since more FADH2-FMN is generated and not consumed quickly enough, the decreased flavin absorption band of FADH2-FMN will blur the isosbestic point after 100 ms, most likely due to a slower two-electron reduction of FMN in the mutant
V567L
little production of NO, lower affinity for L-arginine and N-hydroxy-L-arginine than wild-type
W678A
-
increase in Km-value of tetrahydrobiopterin, decrease in NO synthesis activity, slower building of enzyme heme-NO complex and slower reactivity of heme-dioxy intermediate
W678F
-
increase in Km-value of tetrahydrobiopterin, decrease in NO synthesis activity, slower building of enzyme heme-NO complex and slower reactivity of heme-dioxy intermediate
additional information
I224V
little effect on binding of L-arginie, tetrahydrobiopterin or in electronic properties
I224V
mutation does not greatly alter binding of Arg, (6R)-tetrahydrobiopterin, or alter the electronic properties of the heme or various heme-ligand complexes. I224V displays three heme transitions involving four species as typically occurs in wild-type NOS, the beginning ferrous enzyme, a ferrous-dioxy (FeIIO2) intermediate, FeIIINO, and an ending ferric enzyme. The rate of each transition is increased relative to wild-type, with FeIIINO dissociation being 3.6 times faster
I224V
-
mutation does not greatly alter binding of Arg, (6R)-tetrahydrobiopterin, or alter the electronic properties of the heme or various heme-ligand complexes. I224V displays three heme transitions involving four species as typically occurs in wild-type NOS, the beginning ferrous enzyme, a ferrous-dioxy (FeIIO2) intermediate, FeIIINO, and an ending ferric enzyme. The rate of each transition is increased relative to wild-type, with FeIIINO dissociation being 3.6 times faster
-
S1179D
the phosphomimetic substitution at Ser-1179 doubles maximal synthase activity, partially disinhibits cytochrome c reductase activity, and lowers the EC50(Ca2+) values for calmodulin binding and enzyme activation about 35%
S1179D
mutation augments enzyme activity and increases its sensitivity to heat shock protein 90 (Hsp90). Mutation of Ser1179 to aspartic acid plays a dominant role in changing the sensitivity of the enzyme to NADPH.
additional information
deletion of the autoinhibitory domain doubles the maximum calmodulin-dependent enzyme activity and decreases the EC50(Ca2+) values for calmodulin binding and calmodulin-dependent enzyme activation
additional information
-
deletion of the autoinhibitory domain doubles the maximum calmodulin-dependent enzyme activity and decreases the EC50(Ca2+) values for calmodulin binding and calmodulin-dependent enzyme activation
additional information
-
enhancement of nitric oxide production by association of neuronal nitric oxide synthase with N-methyl-D-aspartate receptors via postsynaptic density 95 proteins in genetically engineered Chinese hamster ovary cells, method development and quantitative analysis, overview
additional information
-
construction of a heterodimer with one subunit being His-tagged
additional information
monomers encoding NOS oxygenase domain lacking the N-terminal 114 residues, His-tagged, expression in Escherichia coli
additional information
-
monomers encoding NOS oxygenase domain lacking the N-terminal 114 residues, His-tagged, expression in Escherichia coli
additional information
-
naturally occuring neuronal mutant with a 105-amino acid deletion in the heme-binding domain as a result of in-frame mutation by specific alternative splicing, contains heme, but shows no L-arginine and NADPH-dependent citrulline-forming activity in presence of Ca2+-promoted calmodulin
additional information
-
construction of eNOS and of iNOS knockout mice, phenotype, overview
additional information
-
generation of mice chimeric for iNOS expression, wild-type animals receive bone marrow cells from CD45.1-expressing congenic wild-type mice, resulting in three different chimeric strains, phenotype with induced colitis, overview
additional information
-
knock out mice deficient for the splice-isoform alpha of neuronal nitric oxide synthase display residual nitric oxide synthase activity and immunosignal
additional information
-
mutant DELTA296nNOS, missing N-terminal leader sequence, no impact on enzyme structure or catalysis, mutant DELTA349nNOS, missing N-terminal leader sequence plus three core motifs, weaker dimer interaction, slowerferric heme production, 10fold poorer affinity towards L-arginine
additional information
-
construction of a truncated mutant lacking the terminal half of the C-terminus, i.e. residues from Ile1413 to Ser1429. The mutation has almost no impact on NADP+ release, flavin reduction, flavin autoxidation, heme reduction, reductase activity, or NO synthesis activity, but does prevent an increase in FMN shielding that normally occurs in response to NADPH binding. Additional removal of the C-terminal alpha-helix, residues 1401 to 1412, significantly increases the NADP+ release rate, flavin autoxidation, and NADPH oxidase activity, and causes hyper-deshielding of the FMN cofactor associated with increased reductase activity and slightly diminished heme reduction and NO synthesis. Further removal of residues downstream from Gly1396, a full C-terminus truncation, amplifies the aforementioned effects and in addition altered NADP+ interaction with FAD, relieves the kinetic suppression on flavin reduction, and further diminishes heme reduction and NO synthesis
additional information
-
knock out mice deficient for the splice-isoform alpha of neuronal nitric oxide synthase display residual nitric oxide synthase activity and immunosignal, phenotype, overview
additional information
the DELTAG810 mutant enzyme shows strongly reduced activity towards nitric oxide synthesis and NADPH oxidation compared to the wild type enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
additional information
-
subunit disassembly and unfolding of the protein following a pH jump from 7.5 to 2.8, kinetic unfolding mechanism of the inducible enzymes' oxygenase domain, the initial step of the reaction is the disruption of the iNOSCOD dimer, to generate heme-bound monomeric species in various degrees of unfolding, which is accompanied by the loss of two tetrahydrobiopterin cofactors, subsequent heme loss generates monomeric apoproteins exhibiting various degrees of unfolding, modeling of the denaturation process, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
-
tetrahydrobiopterin-free enzyme is not stable, therefore reaction is performed at 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate precipitation results in remarkable loss of tetrahydrobiopterin
-
glycerol stabilizes
heat-, diethylether- and alkali-labile, slightly acid resistant cytosolic factor of MW above 100000 and of little charge at neutral pH stabilizes
-
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
-
mutants less stable than wild-type, precipitation during incubation at 15°C, partial stabilization with NaCl, stabilization by purification in presence of L-arginie and tetrahydrobiopterin
-
mutants less stable than wild-type, precipitation during incubation at 15°C, partial stabilization with NaCl, stabilization by purification in presence of L-arginine and tetrahydrobiopterin
very stable against trypsin, reductase domain is much more susceptible to urea than oxygenase domain
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-85°C, 50 mM Tris (pH 7.4) with 10% (v/v) glycerol, 100 mM NaCl, 0.2 mM L-arginine, 0.0002 mM 5,6,7,8-tetrahydro-L-biopterin, 0.02 mM dithiothreitol, and 1 mM 2',3'-AMP (mixed isomers), up to 1 month, no detectable loss of catalytic activity
0°C, crude, t1/2: 2 days, purified t1/2: 2 h, with 1 mg/ml bovine serum albumin and 20% v/v glycerol as stabilizing agents, t1/2: 7 days
-
4°C, in the presence of one or more cytosolic factors at least 24 h stable
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
2',5'-ADP-agarose affinity chromatography
ammonium sulfate precipitation (30% saturation), 2',5'-ADP-affinity chromatography
-
native enzyme from axenic amastigotes by 2',5'-ADP affinity chromatography to homogeneity
-
native enzyme from platelets activated by acetylsalicylic acid, by solubilization with Triton X-100, anion exchange chromatography, and gel filtration, to homogeneity
-
native enzyme from tilapia, by 2',5'-ADP affinity chromatography, ion exchange chromatography, and gel filtration
-
native rat neuronal NOS reductase domain (nNOSred) and the R1400E variant
Ni Sepharose column chromatography, 2',5'-ADP Sepharose column chromatography, and Superdex 200 gel filtration
Ni-NTA Sepharose column chromatography and 2'-5' ADP Sepharose resin column chromatography
partial
recombinant bNOS by ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
recombinant eNOS from Escherichia coli by 2',5'-ADP affinity chromatography
-
recombinant enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
recombinant enzyme oxygenase domain from Escherichia coli in the absence of both Arg and tetrahydrobiopterin
-
recombinant His-tagged construct dNOSr from Escherichia coli strain BL21 by nickel affinity and calmodulin affinity chromatography
-
recombinant His-tagged dNOS from Escherichia coli by nickel affinity and anion exchange chromatography in the presence of L-Arg and H4B
-
recombinant His-tagged or GST-tagged truncated nNOS, comprising residues 1-198, from Escherichia coli by nickel affinity or glutathione affinity chromatography, respectively
-
recombinant His-tagged wild-type enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, recombinant truncation mutant from Escherichia coli strain BL21(DE3) by sequential 2',5'-ADP and calmodulin affinity chromatography
-
recombinant His6-tagged bNOS from Escherichia coli strain BL21(DE3) by ammonium sulfate fractionation, anion exchange chromatography, and gel filtration
-
recombinant His6-tagged soluble enzyme from Escherichia coli strain BL21 (DE3) by nickel affinity chromatography
-
recombinant neuronal enzyme from HEK-293 cells by 2',5'-ADP affinity chromatography to about 90% purity
-
recombinant nNOS from Escherichia coli in absence of tetrahydrobiopterin
recombinant wild-type of inducible liver isoform from Escherichia coli with and without His-tag, requires inclusion of tetrahydrobiopterin in purification buffer
-
sequential affinity chromatography on 2',5'-ADP-agarose and calmodulin Sepharose 4B
-
wild-type and natural mutant, recombinant from Escherichia coli and insect cells
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
bacterial NOS, phylogenetic tree, functional expression in Escherichia coli
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
-
DNA and amino acid sequence determination and analysis, functional expression of the C-terminally His6-tagged soluble enzyme in Escherichia coli strain BL21 (DE3), sequence alignment and comparative modeling
-
endothelial enzyme expressed in Pichia pastoris using a highly inducible alcohol oxidase promoter PAOX1
-
expressed in Escherichia coli BL21(DE3) 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
-
expression of endothelial isoform III in Spodoptera frugiperda cells via baculovirus infection
-
expression of GST-tagged splicing variants alpha and beta in HEK 293 cells
-
expression of His-tagged and GST-tagged truncated nNOS, comprising residues 1-198, in Escherichia coli
-
expression of His-tagged NOS oxygenase domain lacking the N-terminal 114 residues in Escherichia coli
expression of His-tagged wild-type enzyme and untagged truncation mutant enzyme in Escherichia coli strain BL21(DE3)
-
expression of neuronal isoform wild type and mutants C415H, C415A in Spodoptera frugiperda cells via baculovirus infection
-
expression of the C-terminally His-tagged iNOS oxygenase domain, iNOSoxy, in Escherichia coli strain BL21
-
expression of the oxygenase domain of inducible nitric oxide synthase in Escherichia coli
-
gene nos1, quantitative reverse-transcription PCR enzyme expression analysis
gene nos2, recombinant expression of wild-type and mutant enzymes in HEK293 cells or Escherichia coli
inducible liver isoform is expressed in Escherichia coli with and without His-tag, requires coexpression of calmodulin
-
iNOS, DNA and amino acid sequence determination and analysis, phylogenetic analysis
native rat neuronal NOS reductase domain (nNOSred) and the R1400E variant are expressed from plasmid pCRNNR in Escherichia coli BL21(DE3)
neuronal enzyme expressed in Spodoptera frugiperda cells via baculovirus infection
-
neuronal wild-type and natural mutant, specifically expressed in the central nervous system, expression in Escherichia coli and in insect cells of Spodoptera frugiperda via baculovirus infection
-
overexpression of wild-type endothelial enzyme and mutant endothelial enzyme S1179D in Escherichia coli
phylogenetic tree, expression of a His-tagged construct, dNOSr, comprising the dNOS reductase domain and its adjacent calmodulin binding site in Escherichia coli strain BL21
-
rat brain enzyme expressed in human 293 kidney cells transfected with a vector encoding rat brain enzyme
-
stable, functional co-expression of enzyme and NMDA receptors in CHO1 cell plasma membranes, predominantly, and in the cytosol of CHO1() cells lacking postsynaptic density 95 proteins, PSD-95, expression
-
the oxygenase domain of iNOS with a C-terminal His6-tag is expressed in Escherichia coli
the wild type and the DELTAG810 mutant of nNOS are cloned in Escherichia coli strain DH5alpha
transient expression of GFP-tagged isozyme NOS1 in COS-1 cell mitochondria, N-terminally truncated GFP-tagged isozyme NOS1 is localized in the cytosol
-
untagged nNOS dimer protein is expressed using a recombinant baculovirus/Sf9 insect cell system
wild-type endothelial enzyme is expressed in insect cells via baculovirus infection
-
bacterial NOS, phylogenetic tree, functional expression in Escherichia coli
-
bacterial NOS, phylogenetic tree, functional expression in Escherichia coli
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
0.001 mg thyroxin significantly increases nNOS protein level to 178% compared to control
0.01 mM 2-phenyl-ethenesulfonic acid phenyl ester, 2-phenyl-ethenesulfonic acid 4-chlorophenyl ester, and 2-methyl-4-nitro-quinoline 1-oxide inhibit the expression of inducible nitric oxide synthase protein, 4-nitro-quinoline 1-oxide reveals no significant expression-downregulating activity at 0.01 mM
-
0.1 mg 6-n-propyl-2-thyouracil decreases nNOS protein level to 19% compared to control
exposure of primary cortical astrocytes to a low concentration of Mn2+ (0.01 mM) potentiates expression of NOS2 mRNA and protein
expression of both the eNOS protein and gene is significantly reduced in tight-skin 1-mouse skin tissue
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
expression of isozyme NOS1 protein is decreased in the cytoplasmic and plasma membrane fractions, although maintained in the intracellular membrane fraction, in response to high salt
expression of isozyme NOS3 protein is unaffected by high salt
expression of neuronal NOS and endothelial NOS is upregulated during the odontoblastic differentiation of dental papilla cells (DPCs)
in Portunus trituberculatus challenged with the Hematodinium parasite, transcripts in hemocytes are significantly induced at 12 and 24 h, followed by significant suppression at 96 and 192 h
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
investigated the effect of imiquimod (IMQ)-induced psoriatic inflammation on kidney function and inflammation in a murine model. Psoriatic inflammation in mice is associated with kidney dysfunction as reflected by increased serum creatinine and blood urea nitrogen. Kidney dysfunction is paralleled by upregulation of reactive oxygen species (ROS) generating enzymes such as NOX2, NOX4 and iNOS
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
mitogen-activated protein kinase phosphatase-1 may negatively regulate iNOS expression by controlling the expression of microRNA-155 and consequently the signal transducer and activator of transcription pathway via suppressor of cytokine signaling-1
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
nitric oxide synthase activity and expression are decreased in the paraventricular nucleus of pregnant rats
nitric oxide synthase activity is significantly affected in ipsilateral and contralateral testes cells after vasal and epididymal ligation
nitric oxide synthase activity is significantly affected in ipsilateral and contralateral testes cells after vasal and epididymal ligation, eNOS immunoreactivity increases markedly after ipsilateral vasal ligation
treatment with a selective G protein-coupled ER agonist decreases NADPH-diaphorase expression in the supraoptic and paraventricular nuclei of the hypothalamus. Treatment with the selective G protein-coupled estrogen receptor agonist in combination with an antagonist effectively rescues the decrease in NADPH-diaphorase expression in both brain regions
-
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
urothelial and endothelial i-NOS expression are significantly increased in neuromodulated rats
urothelial n-NOS expression is significantly increased in neuromodulated rats
expression of neuronal NOS and endothelial NOS is upregulated during the odontoblastic differentiation of dental papilla cells (DPCs)
expression of neuronal NOS and endothelial NOS is upregulated during the odontoblastic differentiation of dental papilla cells (DPCs)
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
refolding after treatment/equilibration with 5 M urea in presence of L-arginine and tetrahydrobiopterin
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
pharmacology
-
NO synthase can be used to gain insight into the biological role of endogenous agmatine
analysis
by using enzyme NADPH-d histochemistry, a marker for NOS activity, the effect of leptin on NO-producing cells in the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of male Wistar rats is assessed
analysis
-
by using enzyme NADPH-d histochemistry, a marker for NOS activity, the effect of leptin on NO-producing cells in the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of male Wistar rats is assessed
-
medicine
-
enzyme induces relaxation of endothelium-denuded rat aortic rings precontracted with phenylepinephrine, possible participation in pathogenesis of invasive amebiasis
medicine
-
no evidence for altered enzyme function of mutant E298D that could explain endothelial dysfunction associated with the E298D polymorphism
medicine
-
nitric oxide synthase inhibitors, e.g. L-N(G)-nitro-arginine-methylester, may serve as an alternative adjunct with antibiotic therapy for Pseudomonas keratitis, especially for reducing ocular inflammation without affecting the antimicrobial efficacy of the antibiotic
EXTERNAL LINKS (specific for EC-Number 1.14.13.39)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2026.1 (March 2026)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
![DSMZ Digital Diversity]()
![Global Core Biodata Resource]()
![ELIXIR Core Data Resource]()
![German Network for Bioinformatics Infrastructure]()
