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Information on EC 1.14.13.39 - nitric-oxide synthase (NADPH)
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1.14.13.39 nitric-oxide synthase (NADPH)IUBMB Comments
The enzyme consists of linked oxygenase and reductase domains. The eukaryotic enzyme binds FAD, FMN, heme (iron protoporphyrin IX) and tetrahydrobiopterin, and its two domains are linked via a regulatory calmodulin-binding domain. Upon calcium-induced calmodulin binding, the reductase and oxygenase domains form a complex, allowing electrons to flow from NADPH via FAD and FMN to the active center. The reductase domain of the enzyme from the bacterium Sorangium cellulosum utilizes a [2Fe-2S] cluster to transfer the electrons from NADPH to the active center. cf. EC 1.14.14.47, nitric-oxide synthase (flavodoxin).
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Word Map
- 1.14.13.39
- artery
- necrosis
- lipopolysaccharide
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l-name
- lps
- tnf
- cardiovascular
- cox-2
- nitrite
- cyclooxygenase-2
- vessel
- hypertension
- cardiac
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lps-induced
- dismutase
- cerebral
-
vasodilation
- nerve
- aortic
- ischemia
- pulmonary
- prostaglandin
- myocardial
- cgmp
- ng-nitro-l-arginine
- factor-alpha
- coronary
- acetylcholine
- wistar
-
endothelium-dependent
- tnf-alpha
- peroxynitrite
-
contractile
-
neuroprotective
-
lps-stimulated
-
reperfusion
- nf-kappab
-
nitrotyrosine
- microglia
- interferon-gamma
- nitroprusside
- ifn-gamma
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vasoconstriction
-
guanylate
-
vasorelaxation
- il-1beta
-
lipopolysaccharide-induced
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erectile
- endothelin-1
-
guanylyl
- pharmacology
- medicine
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
nos, inducible nitric oxide synthase, endothelial nitric oxide synthase, inducible no synthase, neuronal nitric oxide synthase, inducible nos, endothelial no synthase, endothelial nos, neuronal nos, no-synthase, 
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topREACTION 
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)
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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
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
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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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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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
analysis of catalytic site by Fourier transform infrared spectroscopy, extent of modulation of vibrational modes upon photolysis of CO compound
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
analysis of transition states via stopped-flow spectroscopy
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
analysis of transition states via stopped-flow spectroscopy
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
overall reaction
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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
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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
interaction and electrontransfer between enzyme domains and bound cofactors calmodulin, FMN, FAD, tetrahydrobiopterin, heme, and NADPH, overview
2 L-arginine + 3 NADPH + 3 H+ + 4 O2 = 2 L-citrulline + 2 nitric oxide + 3 NADP+ + 4 H2O
reaction mechanism, NO release and transport, overview, NO formation through sequential electron transfer and the oxidation of L-arginine, in the catalytic process, FMN, FAD, and tetrahydrobiopterin are required as coenzymes, and the presence of Ca2+/calmodulin can aid the electron transfer, isozymes NOS1 and NOS3 perform a similar reaction mechanism
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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
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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
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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
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PATHWAY SOURCE
PATHWAYS