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Enzyme Nomenclature
Information on EC 1.14.13.39 - nitric-oxide synthase (NADPH)
Word Map on EC 1.14.13.39
- 1.14.13.39
- vascular
- macrophage
- artery
- inflammation
- injury
- lipopolysaccharide
- necrosis
- dysfunction
-
anti-inflammatory
- superoxide
- cardiovascular
- hypertension
- cyclooxygenase-2
-
lps-induced
- nitrite
- diabetes
-
proinflammatory
-
l-name
-
tnf-alpha
- aortic
- vessel
-
nf-kappab
- ischemia
-
vasodilation
-
factor-alpha
- prostaglandin
-
ifn-gamma
-
interleukin
- peroxynitrite
- aminoguanidine
-
interferon-gamma
- cgmp
- coronary
- ng-nitro-l-arginine
- microglia
-
tone
- acetylcholine
-
nitrotyrosine
-
endothelium-dependent
-
il-1beta
-
lps-stimulated
-
factor-kappab
-
lipopolysaccharide-induced
- nitroprusside
- tetrahydrobiopterin
-
interleukin-1beta
- ng-monomethyl-l-arginine
- nadph-diaphorase
- nomega-nitro-l-arginine
-
vasorelaxation
- medicine
- pharmacology
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
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EC NUMBER 
COMMENTARY 
1.14.13.39
-
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RECOMMENDED NAME
GeneOntology No.
nitric-oxide synthase (NADPH)
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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)
-
-
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2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
overall reaction
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-
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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
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2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
cytochrome P-450 enzyme; possible mechanism
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2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
cytochrome P-450 enzyme; possible mechanism
-
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
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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
structure-function study of macrophage enzyme
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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
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
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
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
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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
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
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
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
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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 and kinetic mechanism
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2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
reaction and kinetic mechanism
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
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-
redox reaction
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-
-
-
reduction
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
L-arginine,NADPH:oxygen oxidoreductase (nitric-oxide-forming)
Binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin. This eukaryotic enzyme, which is found in plants [4] and animals [1-3], consists of oxygenase and reductase domains that 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. May produce superoxide under certain conditions [3]. cf. EC 1.14.13.165, nitric-oxide synthase [NAD(P)H dependent].
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CAS REGISTRY NUMBER
COMMENTARY
125978-95-2
-
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
shelf fungus, collected from forest in Darjeeling, East Sikkim, India
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3 isoforms exist in bovine aortic endothelial cells differentiated by substrate specificity and Ca2+-dependence
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-
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440194, 440205, 440215, 440216, 440218, 440226, 440233, 440236, 660371, 660662, 660685, 671728, 672524, 673002, 673680, 674451, 684277, 696110, 697713, 698461, 700432, 711779, 724425, 725011
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-
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440192, 440193, 440195, 440198, 440201, 440209, 440217, 440222, 440225, 440226, 440234, 440236, 658793, 672016, 687291, 687548, 696643
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3 isoforms exist in mouse macrophages differentiated by substrate specificity and Ca2+-dependence
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-
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440191, 440192, 440198, 440207, 440208, 440210, 440212, 440213, 440220, 440226, 658119, 659257, 659330, 671728, 672363, 685120, 687615, 697765, 699997, 725652
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-
-
UniProt
Wistar and Wistar-Kyoto rats, and 1 month-old, prehypertensive/spontaneously hypertensive rats
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-
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
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
-
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
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
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
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 + ?
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-
-
-
ir
1-[[2-(dimethylamino-N-oxide)ethyl]amino]-4-[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + NADPH
1,4-bis[[2-(dimethylamino)ethyl]amino]-5,8-dihydroxyanthracene-9,10-dione + ?
-
-
-
-
ir
2 L-arginine + 3 NADPH + 3 H+ + 4 O2
2 citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
-
-
-
-
?
2-hydroxy-1-(4-hydroxyphenyl)guanidine + NADPH + O2
? + NO + NADP+
-
-
-
?
ferricytochrome c + NADPH + O2
ferrocytochrome c + NO + NADP+
-
-
-
-
?
N-hydroxy-L-arginine + H2O2 + tetrahydrobiopterin
? + NADP+
-
-
-
-
?
Ngamma-hydroxy-L-arginine + H2O2
citrulline + Ndelta-cyanoornithine + NO2- + NO3-
-
tetrahydrobiopterin-free
NO2-/NO3- as aerobic decomposition products from NO-
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
L-citrulline + NADP+ + NO + H2O
-
second half reaction
-
-
?
peroxynitrite + 4-hydroxyphenylacetic acid + NADPH + H+
4-hydroxyl-3-nitro-phenylacetic acid + NADP+ + H2O
-
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
product dimers
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2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
the enzyme forms a five-coordinate, high-spin complex with L-arginine and analogues, e.g. N-hydroxy-L-arginine
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
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
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
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a cytokine-inducible, calcium independent and a constitutive, calcium dependent form
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
probably via Nomega-hydroxy-L-arginine
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
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
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
capacity to synthesize NO only through dimerization and binding of heme and tetrahydrobiopterin
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
dimeric structure is required for enzyme activity
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
dimeric structure is required for enzyme activity
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
tetrahydrobiopterin is absolutely required for partial reaction 1
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
specific for NADPH, 5-electron oxidation of L-arginine
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
enzyme of mammalian immune, cardiovascular and neural systems, synthesizing the free radical nitric oxide or a NO-releasing product
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
soluble cytochrome P-450 enzyme in eukaryotes
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
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
-
-
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
-
-
probably via Nomega-hydroxy-L-arginine
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
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
-
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
-
ir
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
specific for NADPH, 5-electron oxidation of L-arginine
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
soluble cytochrome P-450 enzyme in eukaryotes
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
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
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
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
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
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
-
physiological functions and pathophysiology of the isoforms
-
-
?
2,6-dichlorophenolindophenol + NADPH + O2
? + NO + NADP+
-
best substrate, about 10-fold increase in activity in presence of calmodulin
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
overall reaction
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
overall reaction, the interactions between heme-bound NO and the substrates are finely tuned by the geometry of the Fe-ligand structure, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
overall reaction, two-step oxidation of L-arginine using an O2-dependent mechanism, detailed overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
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
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
the electron transfer between cofactors FMN and FAD is reversible
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
overall reaction, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
regulatory mechanism, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
conserved residue Arg1329 of nNOS enables bound NADPH to stabilize the FMN-shielded conformation, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
NO from acetylsalicylic acid-activated enzyme is involved in thrombolysis, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
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
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
substrate and product binding analysis
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
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
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
complete reaction, oxygen stoichiometry, effects of substrate/cofactor binding on the endothelial NOS isoform, eNOS, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
conversion of L-arginine to citrulline and nitric oxide takes place in two steps with N(G)-hydroxy-L-arginine as an intermediate product
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
overall reaction, the interactions between heme-bound NO and the substrates are finely tuned by the geometry of the Fe-ligand structure, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
overall reaction, two-step oxidation of L-arginine using an O2-dependent mechanism, detailed overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
Nomega-hydroxy-L-arginine + NADP+ + H2O
-
first half reaction via intermediate Nomega-hydroxy-L-arginine
-
-
?
L-arginine + NADPH + H+ + O2
Nomega-hydroxy-L-arginine + NADP+ + H2O
-
first half reaction via intermediate Nomega-hydroxy-L-arginine with consecutive appearance of heme-dioxy, ferric heme-NO, and ferric heme species, overview
-
-
?
L-arginine + NADPH + H+ + O2
Nomega-hydroxy-L-arginine + NADP+ + H2O
-
first half reaction
-
-
ir
L-arginine + NADPH + H+ + O2
Nomega-hydroxy-L-arginine + NADP+ + H2O
-
first half reaction via intermediate Nomega-hydroxy-L-arginine
-
-
?
L-arginine + NADPH + H+ + O2
Nomega-hydroxy-L-arginine + NADP+ + H2O
-
first half reaction via intermediate Nomega-hydroxy-L-arginine
-
-
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
-
-
-
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
-
-
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
-
-
-
-
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
-
-
-
?
L-arginine + NADPH + O2 + tetrahydrobiopterin
citrulline + NO + NADP+ + ?
-
-
-
-
-
L-homoarginine + NADPH + O2
?
-
constitutive endothelial membrane-bound and inducible soluble macrophage enzyme
-
-
?
L-homoarginine + NADPH + O2
?
-
constitutive endothelial membrane-bound and inducible soluble macrophage enzyme
-
-
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
best substrate
-
-
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
best substrate
-
-
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
substrate is intermediate between reaction 1 and 2 to form citrulline and NO from L-arginine
-
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
reaction is possible without tetrahydrobiopterin, can also use H2O2 instead of NADPH and O2
-
?
Ngamma-hydroxy-L-arginine + NADPH + O2
citrulline + NADP+ + NO
-
substrate is intermediate between reaction 1 and 2 to form citrulline and NO from L-arginine
-
-
ir
nitroblue tetrazolium + NADPH
nitroblue tetrazolium-flavazone + NADP+
-
NADPH-diaphorase reaction
-
?
nitroblue tetrazolium + NADPH
nitroblue tetrazolium-flavazone + NADP+
-
NADPH-diaphorase reaction
-
?
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
second half reaction via intermediate Nomega-hydroxy-L-arginine
-
-
-
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
second half reaction via intermediate Nomega-hydroxy-L-arginine
-
-
-
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
second half reaction via intermediate Nomega-hydroxy-L-arginine
-
-
-
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
second half reaction via intermediate Nomega-hydroxy-L-arginine
-
-
-
Nomega-hydroxy-L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
second half reaction via intermediate Nomega-hydroxy-L-arginine, FeII and FeII-NO complexes bind Nomega-hydroxy-L-arginine, overview
-
-
-
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
-
-
-
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
-
-
-
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
-
-
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
wild-type and mutants
-
-
?
oxidized cytochrome c + NADPH + O2
reduced cytochrome c + NADP+ + H2O
-
reaction is enhanced by addition of calmodulin at 0.0002 mM
-
-
?
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
mechanisms of oxygen activation by NOSs, overview
-
-
-
additional information
?
-
-
the bacterial NOS enzymes have no attached flavoprotein domain to reduce their heme and so must rely on unknown bacterial proteins for electrons
-
-
-
additional information
?
-
-
enzyme shows also superoxide formation activity, uneffected by L-arginine, inhibited by tetrahydrobiopterin and diphenyleneiodonium
-
-
-
additional information
?
-
-
enzyme shows also superoxide formation activity
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
postsynaptic density 95 proteins mediate the complex formation of neuronal nitric oxide synthase and N-methyl-D-aspartate receptors
-
-
-
additional information
?
-
-
dNOS participates in essential developmental and behavioral aspects of the fruit fly
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
a oxygenase domain of dNOS complex with ferrous heme-NO is relatively unreactive toward O2
-
-
-
additional information
?
-
-
crude, boiled or ethanolic and dried extracts of Ganoderma applanatum show antioxidant activity, inhibition of lipid peroxidation, and potent hydroxylradical scavenging activity, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
-
neuronal NO synthase may be involved in the pathogenesis of acute lung injury after smoke inhalation injury followed by bacterial instillation in the airway
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
calmodulin-controlled isoforms are signal generators, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
genetic regulation, mechanism, eNOS expression is controlled by both histone acetylation and lysine 4 methylation of histone H3 at eNOS proximal promoter regions, overview
-
-
-
additional information
?
-
both oxyFMN and oxygenase domain activity are measured by following H2O2-supported oxidation of Nomega-hydroxy-L-Arg, L-NOHA, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
the enzyme might be involved in the infectivity and/or escaping mechanism of the parasite
-
-
-
additional information
?
-
-
Ngamma-hydroxylation is the first step of the reaction, Ngamma-hydroxy-L-arginine being an intermediate in the L-arginine to NO pathway
-
-
-
additional information
?
-
-
dimeric enzyme and subunits are equivalent in catalyzing electron transfer from NADPH to cytochrome c, dichlorophenolindiphenol, and ferricyanide
-
-
-
additional information
?
-
-
calmodulin-controlled isoforms are signal generators, overview
-
-
-
additional information
?
-
-
both oxyFMN and oxygenase domain activity are measured by following H2O2-supported oxidation of Nomega-hydroxy-L-Arg, L-NOHA, overview
-
-
-
additional information
?
-
-
inducible nitric-oxide synthase-derived NO contributes to the pathophysiology of intestinal inflammation in the colon
-
-
-
additional information
?
-
-
iNOS modulates endothelin-1-dependent release of prostacyclin and inhibition of platelet aggregation ex vivo in the mouse, overview
-
-
-
additional information
?
-
-
nitric-oxide synthase 2 interacts with CD74 and inhibits its cleavage by caspase during dendritic cell development
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
interaction between peroxynitrite and the oxygenase domain of inducible NOS
-
-
-
additional information
?
-
eNOS is an important negative regulator of AMP-activated protein kinase phosphorylation and intracellular H2O2 generation in endothelial cells
-
-
-
additional information
?
-
-
the enzyme exhibits NADPH-diaphorase activity, uncoupled from nitric oxide synthase activity
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
calmodulin-controlled isoforms are signal generators, overview
-
-
-
additional information
?
-
-
caveolin-1 is a prominent NOS-interacting protein in rat polymorphonuclear neutrophils
-
-
-
additional information
?
-
NO is implicated in the pathogenesis of liver cirrhosis, overview
-
-
-
additional information
?
-
both oxyFMN and oxygenase domain activity are measured by following H2O2-supported oxidation of Nomega-hydroxy-L-Arg, L-NOHA, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
the reduced recombinant trunaction mutant nNOSr performs autooxidation in presence of NADPH, interactions, overview
-
-
-
additional information
?
-
-
the enzyme exhibits NADPH-diaphorase activity, uncoupled from nitric oxide synthase activity
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
-
mechanisms of oxygen activation by NOSs, overview
-
-
-
additional information
?
-
-
the reductase domain has a broad substrate specificity, catalyzes a moderate Ca2+/calmodulin independent hydroxylation when the enzyme is reconstituted with purified P-450
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
P29474
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
a cytokine-inducible, calcium independent and a constitutive, calcium dependent form
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
P29477
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
P29477
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
enzyme of mammalian immune, cardiovascular and neural systems, synthesizing the free radical nitric oxide or a NO-releasing product
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
soluble cytochrome P-450 enzyme in eukaryotes
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
P29476
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
Q06518
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
acts as signal molecule for neurotransmission, vasorelaxation, and cytotoxity
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
soluble cytochrome P-450 enzyme in eukaryotes
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
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
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
-
-
-
?
2 L-arginine + 3 NADPH + 4 O2 + 3 H+
2 L-citrulline + 2 NO + 3 NADP+ + 4 H2O
-
physiological functions and pathophysiology of the isoforms
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
Q9BDQ7
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
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
overall reaction, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
regulatory mechanism, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
NO from acetylsalicylic acid-activated enzyme is involved in thrombolysis, overview
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
L-arginine + NADPH + H+ + O2
citrulline + nitric oxide + NADP+ + H2O
-
-
-
-
?
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
enzyme shows also superoxide formation activity
-
-
-
additional information
?
-
-
postsynaptic density 95 proteins mediate the complex formation of neuronal nitric oxide synthase and N-methyl-D-aspartate receptors
-
-
-
additional information
?
-
-
dNOS participates in essential developmental and behavioral aspects of the fruit fly
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
crude, boiled or ethanolic and dried extracts of Ganoderma applanatum show antioxidant activity, inhibition of lipid peroxidation, and potent hydroxylradical scavenging activity, overview
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
-
neuronal NO synthase may be involved in the pathogenesis of acute lung injury after smoke inhalation injury followed by bacterial instillation in the airway
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
P29474
calmodulin-controlled isoforms are signal generators, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
genetic regulation, mechanism, eNOS expression is controlled by both histone acetylation and lysine 4 methylation of histone H3 at eNOS proximal promoter regions, overview
-
-
-
additional information
?
-
-
the enzyme might be involved in the infectivity and/or escaping mechanism of the parasite
-
-
-
additional information
?
-
-
calmodulin-controlled isoforms are signal generators, overview
-
-
-
additional information
?
-
-
inducible nitric-oxide synthase-derived NO contributes to the pathophysiology of intestinal inflammation in the colon
-
-
-
additional information
?
-
-
iNOS modulates endothelin-1-dependent release of prostacyclin and inhibition of platelet aggregation ex vivo in the mouse, overview
-
-
-
additional information
?
-
-
nitric-oxide synthase 2 interacts with CD74 and inhibits its cleavage by caspase during dendritic cell development
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
P70313
eNOS is an important negative regulator of AMP-activated protein kinase phosphorylation and intracellular H2O2 generation in endothelial cells
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
P29476
calmodulin-controlled isoforms are signal generators, overview
-
-
-
additional information
?
-
-
caveolin-1 is a prominent NOS-interacting protein in rat polymorphonuclear neutrophils
-
-
-
additional information
?
-
Q06518
NO is implicated in the pathogenesis of liver cirrhosis, overview
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
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
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
additional information
?
-
-
NO represents the endogenous activator of soluble guanylyl cyclase
-
-
-
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
-
activity is correlated directly to bound biopterin concentration; 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
-
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
5,6,7,8-tetrahydro-L-biopterin
-
absolute requirement, recombinant from Pichia pastoris
5,6,7,8-tetrahydro-L-biopterin
-
required; required for the first partial reaction, formation of NG-hydroxy-L-arginine
5,6,7,8-tetrahydro-L-biopterin
-
-
5,6,7,8-tetrahydro-L-biopterin
-
-
Calmodulin
-
activation, potent stimulator of purified, not crude, enzyme preparation
Calmodulin
-
NADPH-diaphorase activity of the enzyme is Ca2+/calmodulin independent
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
-
Ca2+/calmodulin is required for superoxide formation in absence of tetrahydropterin
Calmodulin
-
15fold stimulation of cytochrome c reduction of wild-type and mutants C415A and C415H; Ca2+/calmodulin stimulates cytochrome c reductase activity
Calmodulin
-
no stimulation with exogenous calmodulin, inducible isoform from liver
Calmodulin
-
enzyme-bound, the binding sequence links the two enzyme domains
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
Calmodulin
-
in the absence of calmodulin, the wild type enzyme activity is less than 15% of the maximum calmodulin-dependent values
FAD
-
the enzyme bears Ca2+/calmodulin dependent FAD and FMN containing reductase domain which transfers electrons from NADPH to a variety of acceptors
FAD
-
1 mol per mol of enzyme subunit; FAD containing flavoprotein; slight activation by exogeneous FAD
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
FMN
-
the enzyme bears Ca2+/calmodulin dependent FAD and FMN containing reductase domain which transfers electrons from NADPH to a variety of acceptors
FMN
-
wild-type and mutant C415H contain 0.8 and 0.9 mol per mol of subunit, respectively
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
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
-
requirement, specific for, NADPH-diaphorase activity requires higher NADPH concentrations than nitric oxide formation
NADPH
-
at high concentration inhibits dimer reconstitution from subunits; dependent on
NADPH
-
binding structure of NADP(H) to wild-type and truncation mutant enzyme lacking parts of the C-terminus, overview
NADPH
-
-
440194, 440205, 440216, 440218, 440219, 440236, 671728, 672524, 674558, 684277, 696110, 697713, 698461, 699439, 700432
NADPH
-
-
440190, 440191, 440192, 440198, 440203, 440208, 440213, 440220, 440228, 440230, 440236, 658119, 659257, 659330, 671278, 671728, 672363, 672524, 674558, 675257, 677252, 686293, 687615, 687697, 698484, 698852, 699996, 699997, 700433
NADPH
-
-
440192, 440193, 440195, 440198, 440200, 440201, 440206, 440209, 440217, 440219, 440221, 440222, 440225, 440234, 440236, 440238, 440239, 658119, 659336, 672016, 672524, 673662, 674558, 684317, 686293, 687548, 687727, 688600, 696643, 701000, 701194
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
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; insoluble enzyme; macrophage enzyme
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; insoluble enzyme; macrophage enzyme
Ca2+
-
cerebellum enzyme is Ca2+-dependent; retina enzyme is dependent on Ca2+
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, heme–substrate 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
-
mouse macrophage enzyme: cytochrome P-450 type hemoprotein; protoporphyrin IX heme
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
-
0.9-1.2 mol heme per mol of dimer; heme-iron; protoporphyrin IX heme; required
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
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INHIBITORS
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
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-n-propyl-2-thyouracil
-
0.1 mg 6-n-propyl-2-thyouracil decreases nNOS activity to 45% compared to control
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
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
-
;
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
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
-
endothelial and neuronal isoforms: reversible inhibition; L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site
Ngamma-monomethyl-L-arginine
-
inducible isoform: after preincubation irreversible, time- and concentration-dependent inactivation, without preincubation reversible inhibition; L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site
Ngamma-monomethyl-L-arginine
-
endothelial and neuronal isoforms: reversible inhibition; in presence of tetrahydrobiopterin 0.004 mM the neuronal isoform is inactivated; L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site
Ngamma-nitro-L-arginine
-
inhibits citrulline formation, not cytochrome c reduction
Ngamma-nitro-L-arginine
-
irreversible inactivation of neuronal and endothelial isoform after preincubation, unaffected by tetrahydrobiopterin; L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site
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
-
irreversible inactivation of neuronal and endothelial isoform after preincubation, unaffected by tetrahydrobiopterin; L-arginine protects against enzyme inactivation, thus inactivation occurs at or near active site
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
additional information
-
not inhibitory: N-nitro-D-arginine methyl ester at 0.5 mM
-
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
-
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
-
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
-
fibroblast growth factor-2 treatment up-regulates the enzyme in tectume, but down-regulates it in the optic nerve, overview
-
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
-
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
-
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
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
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
-
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
-
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
0.01
menadione
-
FAD-FMN domain, absence of calmodulin; FAD-FMN domain, presence of calmodulin
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 NO and substrate binding, recombinant enzyme
-
additional information
additional information
-
kinetics of NO and substrate binding, recombinant enzyme
-
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
-
kinetic analysis of the interaction between peroxynitrite and the oxygenase domain of inducible NOS at three different pH values, 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 heme-NO complex formation in the stopped-flow reaction
-
additional information
additional information
-
kinetics, rapid-freeze method, overview
-
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
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.28
NADPH
Rattus norvegicus
-
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
Rattus norvegicus
-
DELTAG810 mutant enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
2.33
NADPH
Rattus norvegicus
-
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
Rattus norvegicus
-
wild type enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
0.033
nitric oxide
Rattus norvegicus
-
DELTAG810 mutant enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
0.055
nitric oxide
Rattus norvegicus
-
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
Rattus norvegicus
-
wild type enzyme, in 25 mM potassium phosphate, pH 7.5, with 100 mM KCl, at 25°C
1.23
nitric oxide
Rattus norvegicus
-
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
0.000085
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
P29477
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
P29477
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
P29477
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
P29477
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
P29477
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
P29477
IC50: 0.00025mM
0.00053
6-chloro-4-(3-methylamino-propoxy)-1-benzopyran-2-one trifluoroacetic acid salt
Rattus norvegicus
-
IC50: 0.00053mM
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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
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
7.5
7.6
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10
22
25
30
37
37
-
assay at
37
-
assay at
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
mainly in the lateral soma rind, surrounding the sensory glomeruli, partially in association with the antennal mechanosensory and motor neuropil
-
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
-
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
-
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
constitutive expression of Ca22+/calmodulin-dependent neuronal nitric oxide synthase in the central and peripheral nervous system
-
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
n the skin, eNOS is present in the epidermal layer, hair follicles and also in the endothelial cells lining the blood vessels
-
distribution, overview, before and after axotomy and fibroblast growth factor-2 application
-
eNOS immunoreactivity is detected in germ cells, Sertoli cells, Leydig cells and vascular endothelial cells of the testis; iNOS positive cells are detected in seminiferous epithelial cells, especially in germ cells of the testis
-
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
additional information
-
Pseudomonas aeruginosa stimulates expression of inducible nitric oxide synthase by A-549 cells
-
-
440190, 440191, 440192, 440196, 440197, 440198, 440203, 440210, 440212, 440213, 440220, 440228, 440232, 440236, 671278, 674558, 686293, 697042
-
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
-
Ca2+-dependent isoform; 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
-
-
-
-
iNOS is more frequently expressed in osteoarthritic than in normal chondrocytes, iNOS expression and activity in osteoarthritic chondrocytes is sub-maximal; nNOS is more frequently expressed in normal than in osteoarthritic chondrocytes
-
isoform III; liver, lung, adrenal glandcolon, isoform II; lung, uterus, stomach
-
vascular, constitutive expression of the endothelial isozyme in endothelial cells
-
isoform III; liver, lung, adrenal glandcolon, isoform II; lung, uterus, stomach
temporal expression of hepatic iNOS in liver cirrhosis, induced in rats by chronic bile duct ligation, overview
-
central nervous system, natural variant with 105-amino acid deletion in the heme-binding domain
-
distribution, overview, in retinorecipient tectal layer, before and after axotomy and fibroblast growth factor-2 application
-
nNOS, nerve cell bodies and neuronal fibers
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
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
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; activity of constitutive enzymes is regulated by binding of calmodulin and Ca2+, the inducible enzyme is regulated by binding of calmodulin, not by Ca2+
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
additional information
-
nNOS splicing variants tissue distribution, immunohistochemic analysis, overview
additional information
-
no activity in gill, intestine, and liver
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
additional information
expression analysis in isolated hepatocytes, healthy liver, and cirrhotic liver, overview
additional information
-
nNOS splicing variants tissue distribution, immunohistochemic analysis, overview
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
-
additional information
no expression in salivary glands and the gland of Leiblein
additional information
-
no expression in salivary glands and the gland of Leiblein
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
additional information
-
immunohistochemic analysis of enzyme distribution, overview
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
-
-
constitutive endothelial enzyme: predominantly membrane-bound, inducible macrophage enzyme: equally distributed between cytosol and membrane, small constitutive membrane-bound portion in murine macrophages
-
constitutive endothelial enzyme: predominantly membrane-bound, inducible macrophage enzyme: equally distributed between cytosol and membrane, small constitutive membrane-bound portion in murine macrophages
-
total NOS activity is enriched in the intracellular membrane fraction at normal salt diet; total NOS activity is enriched in the intracellular membrane fraction at normal salt diet
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
-
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
-
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; activity of constitutive enzymes is regulated by binding of calmodulin and Ca2+, the inducible enzyme is regulated by binding of calmodulin, not by Ca2+
-
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
-
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
-
additional information
-
subcellular distribution of NOS and caveolin-1, nNOS and iNOS are co-localized with caveolin-1, overview
-
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
-
-
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
-
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PDB
SCOP
CATH
ORGANISM
UNIPROT
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
89000
-
2 * 89000, nNOS, SDS-PAGE, bands of 47 kDa and 29 kDa also occur
120000
135000
150000
152000
160000
200000
300000
additional information
-
dissociates irreversibly into subunits in the absence of L-arginine, FAD and tetrahydrobiopterin
150000
-
1 * 150000, SDS-PAGE; 2 * 150000, SDS-PAGE, gel filtration at high salt concentration
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SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
monomer
additional information
?
-
130000-133000, isoforms II and III, amino acid sequence determination; x * 160000, isoform I, amino acid sequence determination
?
-
130000-133000, isoforms II and III, amino acid sequence determination; x * 160000, isoform I, amino acid sequence determination
dimer
-
subunit disassembly and unfolding of the protein following a pH jump from 7.5 to 2.8
dimer
-
2 * 89000, nNOS, SDS-PAGE, bands of 47 kDa and 29 kDa also occur
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
-
significant amino acid sequence homology to NADPH-cytochrome P-450-type hemoprotein
additional information
-
D-arginine inhibits reconstitution of dimer from subunits; dissociation of dimer into subunits at pH 6.8; subunit composition of dimeric enzyme
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; dimeric structure is required for enzyme activity, interaction between subunits via oxygenase domains
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
-
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
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
flavoprotein
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
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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
-
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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
672016
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
-
tetrahydrobiopterin-free enzyme is not stable, therefore reaction is performed at 25°C
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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
-
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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
-
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2',5'-ADP-agarose affinity chromatography
ammonium sulfate precipitation (30% saturation), 2',5'-ADP-affinity chromatography
-
dimeric enzyme and subunits; from interferon-gamma- and lipopolysaccharide-activated macrophage
-
inducible form from macrophage; sequential anion-exchange-, affinity chromatogaphy
-
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
-
Ni Sepharose column chromatography, 2',5'-ADP Sepharose column chromatography, and Superdex 200 gel filtration; 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
recombiant His-tagged dNOS from Escherichia coli by nickel affinity and anion exchange chromatography in the presence of L-Arg and H4B
-
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 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 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
-
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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; expressed in Escherichia coli BL21(DE3) cells
-
expressed in SH-SY5Y cells; expressed in SH-SY5Y cells; expressed in SH-SY5Y cells
-
expression in HUVE cells, vascular smooth muscle cells, and in HeLa cells, DNA methylation of proximal promoter sequences of eNOS promoter-beta-Gal fusion contructs in trangenic mice is not essential for cell-specific expression, endothelial cells are highly enriched in acetylated H3 and acetylated H4 at the eNOS promoter altering the promoter function and expression
-
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
-
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
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
-
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
-
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
-
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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
-
in the peripheral lung of chronic obstructive pulmonary disease patients iNOS mRNA expression is increased at earlier stages of the disease but decreases in the most severe patients, pro-inflammatory cytokine-induced iNOS expression is decreased by oxidative stress, such as H2O2, cigarette smoke conditioned media, and the peroxyntrite generator SIN1; lung tissue from patients with severe and very severe chronic obstructive pulmonary disease have graded increases in nNOS (mRNA and protein) compared with non-smokers and normal smokers
-
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; 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
-
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 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
-
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
I224V
-
little effect on binding of L-arginie, tetrahydrobiopterin or in electronic properties
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%
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
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
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
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
-
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
monomers encoding NOS oxygenase domain lacking the N-terminal 114 residues, His-tagged, expression in Escherichia coli
additional information
-
construction of a heterodimer with one subunit being His-tagged
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
-
construction of eNOS and of iNOS knockout mice, phenotype, overview
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
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Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
refolding after treatment/equilibration with 5 M urea in presence of L-arginine and tetrahydrobiopterin
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
pharmacology
-
NO synthase can be used to gain insight into the biological role of endogenous agmatine
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
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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
LINKS TO OTHER DATABASES (specific for EC-Number 1.14.13.39)
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