Information on EC 1.6.5.10 - NADPH dehydrogenase (quinone)

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
1.6.5.10
-
RECOMMENDED NAME
GeneOntology No.
NADPH dehydrogenase (quinone)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
NADPH + H+ + a quinone = NADP+ + a quinol
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
NADPH:(quinone-acceptor) oxidoreductase
A flavoprotein [1, 2]. The enzyme from Escherichia coli is specific for NADPH and is most active with quinone derivatives and ferricyanide as electron acceptors [3]. Menaquinone can act as acceptor. The enzyme from hog liver is inhibited by dicoumarol and folic acid derivatives but not by 2,4-dinitrophenol [1].
CAS REGISTRY NUMBER
COMMENTARY hide
37256-37-4
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain ATCC51449
-
-
Manually annotated by BRENDA team
strain ATCC51449
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
hog
-
-
Manually annotated by BRENDA team
gene arsH
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
the enzyme is a member of the family of NADPH-dependent FMN reductases
malfunction
-
arsH mutants are sensitive to the oxidizing agent menadione
physiological function
additional information
-
although the enzyme is able to stabilize the anionic semiquinone form of the FMN, reduction of quinones involves the hydroquinone form of the flavin cofactor, and the enzymatic reaction occurs through a ping pong-type mechanism. ArsH is able to catalyze one-electron reactions (oxygen and cytocrome c reduction), involving the FMN semiquinone form, but with lower efficiency
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R,S)-camphorquinone + NADPH + H+
(R,S)-camphorquinone + NADP+
show the reaction diagram
-
-
-
?
1,2-naphthoquinone + NADPH + H+
1,2-naphthoquinol + NADP+
show the reaction diagram
1,4-benzoquinone + NADPH + H+
1,4-benzoquinol + NADP+
show the reaction diagram
1,4-naphthoquinone + NADPH + H+
1,4-naphthoquinol + NADP+
show the reaction diagram
2 ferricyanide + NADPH
2 ferrocyanide + NADP+ + H+
show the reaction diagram
2,3-dimethoxy-5-methyl-1,4-benzoquinone + NADPH + H+
2,3-dimethoxy-5-methyl-1,4-benzoquinol + NADP+
show the reaction diagram
-
-
-
-
?
2,6-dichlorophenolindophenol + NADPH + H+
reduced 2,6-dichlorophenolindophenol + NAD(P)+
show the reaction diagram
-
very low activity with NADH
-
-
?
2-methyl-1,4-naphthoquinone + NADPH + H+
2-methyl-1,4-naphthoquinol + NADP+
show the reaction diagram
2-methyl-5-hydroxy-1,4-naphthoquinone + NADPH + H+
2-methyl-5-hydroxy-1,4-naphthoquinol + NADP+
show the reaction diagram
-
-
-
-
?
5-hydroxy-1,4-naphthoquinone + NADPH + H+
5-hydroxy-1,4-naphthoquinol + NADP+
show the reaction diagram
5-hydroxy-2-methyl-1,4-naphthoquinone + NADPH + H+
5-hydroxy-2-methyl-1,4-naphthoquinol + NADP+
show the reaction diagram
-
-
-
-
?
9,10-phenanthrenequinone + NADPH + H+
9,10-phenanthrenequinol + NADP+
show the reaction diagram
acenaphthenequinone + NADPH + H+
acenaphthenequinol + NADP+
show the reaction diagram
-
-
-
?
benzoquinone + NADPH
benzohydroquinone + NADP+
show the reaction diagram
-
specific for NADPH
-
-
?
dichlorophenolindophenol + NADPH + H+
? + NADP+
show the reaction diagram
-
about 15% of the activity with menadione
-
-
?
menadione + NADPH + H+
? + NADP+
show the reaction diagram
-
two-electron transfer mechanism from NADPH to quinone
-
-
?
menadione + NADPH + H+
menadiol + NADP+
show the reaction diagram
NADH + acceptor
NADH + reduced acceptor
show the reaction diagram
-
no activity
-
-
-
NADH + Fe(CN)63-
NAD+ + Fe(CN)63-
show the reaction diagram
-
with NADH the actuvity is less than 10% of the activity with NADPH
-
-
?
NADH + H+ + 1,4-naphthoquinone
NAD+ + 1,4-naphthoquinol
show the reaction diagram
-
with NADH the activity is about 15% of the activity with NADPH
-
-
?
NADH + H+ + coenzyme Q0
NAD+ + reduced coenzyme Q0
show the reaction diagram
-
with NADH the activity is less than 10% of the activity with NADPH
-
-
?
NADH + H+ + coenzyme Q1
NAD+ + reduced coenzyme Q1
show the reaction diagram
-
with NADH the activity is less than 10% of the activity with NADPH
-
-
?
NADH + H+ + dichlorophenolindophenol
NAD+ + reduced dichlorophenolindophenol
show the reaction diagram
-
with NADH the actuvity is about 15% of the activity with NADPH
-
-
?
NADH + menadione
NAD+ + ?
show the reaction diagram
-
with NADH the activity is less than 10% of the activity with NADPH
-
-
?
NADPH + acceptor
NADP+ + reduced acceptor
show the reaction diagram
NADPH + H+ + 1,4-benzoquinone
NADP+ + 1,4-benzohydroquinol
show the reaction diagram
no activity with NADH
-
-
?
NADPH + H+ + 1,4-naphthoquinone
NADP+ + 1,4-naphthohydroquinone
show the reaction diagram
-
-
-
?
NADPH + H+ + 1,4-naphthoquinone
NADP+ + 1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2,3-dichloro-5,6-dicyano-1,4-benzoquinone
NADP+ + 2,3-dichloro-5,6-dicyano-1,4-benzoquinol
show the reaction diagram
-
-
-
?
NADPH + H+ + 2,5-dimethyl-4-benzoquinone
NADP+ + 2,5-dimethyl-4-benzoquinonl
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2-hydroxy-1,4-naphthoquinone
NADP+ + 2-hydroxy-1,4-naphthoquinol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + a quinone
NADP+ + a quinol
show the reaction diagram
-
the catalytic cycle of ArsH consists of the acceptance of two electrons from NADPH to reduce the flavin cofactor (reductive half-reaction) and the transfer of these electrons to an acceptor (oxidative half-reaction)
-
-
?
NADPH + H+ + anthraquinone-2-sulfonate
NADP+ + ?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + coenzyme Q0
NADP+ + reduced coenzyme Q0
show the reaction diagram
-
-
-
-
?
NADPH + H+ + coenzyme Q1
NADP+ + reduced coenzyme Q1
show the reaction diagram
-
-
-
-
?
NADPH + H+ + coenzyme Q10
NADP+ + reduced coenzyme Q10
show the reaction diagram
-
-
-
-
?
NADPH + H+ + cytochrome c
NADP+ + reduced cytochrome c
show the reaction diagram
-
-
-
-
?
NADPH + H+ + dibromothymoquinone
NADP+ + dibromothymoquinol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + dichlorophenolindophenol
NADP+ + reduced dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + duroquinone
NADP+ + durohydroquinone
show the reaction diagram
-
-
-
?
NADPH + H+ + duroquinone
NADP+ + duroquinol
show the reaction diagram
NADPH + H+ + menadione
NADP+ + ?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + menadione
NADP+ + menadiol
show the reaction diagram
NADPH + H+ + menadione
NADP+ + reduced menadiol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + methyl-p-benzoquinone
NADP+ + methyl-p-benzohydroquinone
show the reaction diagram
-
-
-
?
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
?
NADPH + H+ + p-benzoquinone
NADP+ + p-benzohydroquinone
show the reaction diagram
-
-
-
?
NADPH + H+ + phenyl-1,4-benzoquinone
NADP+ + phenyl-1,4-benzoquinol
show the reaction diagram
-
-
-
?
NADPH + H+ + quinone
NADP+ + ?
show the reaction diagram
-
TNF alpha and LPS induce Nqo1 mRNA expression
-
-
?
NADPH + H+ + quinone
NADP+ + quinol
show the reaction diagram
-
-
-
?
NADPH + H+ + ubiquinone-1
NADP+ + ubihydroquinone-1
show the reaction diagram
-
-
-
?
oxidized dichlorophenolindophenol + NADPH + H+
reduced dicholorophenolindophenol + NADP+
show the reaction diagram
-
-
-
-
?
ubiquinone-0 + NADPH + H+
ubiquinol-0 + NADP+
show the reaction diagram
-
two-electron transfer mechanism from NADPH to quinone
-
-
?
ubiquinone-1 + NADPH + H+
ubiquinol-1 + NADP+
show the reaction diagram
-
two-electron transfer mechanism from NADPH to quinone
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NADPH + H+ + a quinone
NADP+ + a quinol
show the reaction diagram
-
the catalytic cycle of ArsH consists of the acceptance of two electrons from NADPH to reduce the flavin cofactor (reductive half-reaction) and the transfer of these electrons to an acceptor (oxidative half-reaction)
-
-
?
NADPH + H+ + cytochrome c
NADP+ + reduced cytochrome c
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the enzyme plays an important role in managing oxidative stress and contributes to successful colonization of the host
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cytochrome b558
-
gp91phox and p22phox are integral membrane proteins that form a heterodimeric flavocytochrome b558, the catalytic core of the enzyme
-
cytochrome c
-
-
flavin
NADH
-
activity is 15% or less of the activity with NADPH
additional information
-
no cofactor: NADH, FMN
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(N-methyl-4'-pyridyl) porphyrin
-
iron tetrakis, FeTMPyP, no inhibitory activity
1,10-phenanthroline
-
1 mM, 72% inhibition
1-(2-thenoyl)-3,3,3-trifluoracetone
-
1 mM, 89% inhibition
2,4-Dinitrophenol
-
1 mM, 86% inhibition
4-(2-aminoethyl)benzenesulfonylfluoride
4-(amidino)benzenesulfonylfluoride
-
1.49 mM, 50% inhibition
8-hydroxyquinoline
-
0.3 mM, 80% inhibition
ATP
-
0.2 mM, 75% inhibition
Cibacron blue F3GA
-
the 1,4-naphthoquinone activity of CBR4 is potently inhibited, competitive with respect to NADPH
Co2+
-
0.5 mM
dicoumarol
diphenylene iodonium
-
inhibition of the NADPH oxidase complex activity reduces the increase of superoxide production induced by palmitic acid
diphenyleneiodonium chloride
-
a flavoprotein inhibitor
EDTA
-
0.15 mM, 80% inhibition
Folic acid derivatives
-
-
HgCl2
-
0.02 mM
iodoacetate
-
3 mM
L-N6-(1-iminoethyl) lysine
-
no inhibitory activity
PCMB
-
0.1 mM
Procion red HE3B
-
the 1,4-naphthoquinone activity of CBR4 is potently inhibited, competitive with respect to NADPH
Zn2+
-
0.5 mM
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-methylene-4-butyrolactone
-
25fold induction
beta-naphthoflavone
-
-
lithiumdodecylsulfate
-
-
additional information
-
palmitic acid and antimycin A induce the enzyme and superoxide production
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.003 - 0.009
1,2-naphthoquinone
0.0019 - 1.8
1,4-benzoquinone
0.0065
1,4-Naphthoquinone
-
pH 7.4, 25C
298.2
2,3-dichloro-5,6-dicyano-1,4-benzoquinone
25C, pH 6.5
0.0044
2,3-dimethoxy-5-methyl-1,4-benzoquinone
-
pH 7.4, 25C
0.0013
2,5-dimethyl-4-benzoquinone
-
pH 8.0, 25C, recombinant His-tagged enzyme
0.0237
2-Hydroxy-1,4-naphthoquinone
-
pH 8.0, 25C, recombinant His-tagged enzyme
0.003
2-methyl-1,4-naphthoquinone
-
pH 7.4, 25C
0.0045
5-hydroxy-1,4-naphthoquinone
-
pH 7.4, 25C
0.0043
5-Hydroxy-2-methyl-1,4-naphthoquinone
-
pH 7.4, 25C
0.0016 - 0.056
9,10-phenanthrenequinone
0.0345
anthraquinone-2-sulfonate
-
pH 8.0, 25C, recombinant His-tagged enzyme
0.0119
coenzyme Q10
-
pH 8.0, 25C, recombinant His-tagged enzyme
0.0012
dibromothymoquinone
-
pH 8.0, 25C, recombinant His-tagged enzyme
0.0028 - 0.019
duroquinone
647.5
hydroquinone
25C, pH 6.5
0.0057 - 0.036
menadione
0.006 - 0.046
NADPH
728.6
phenyl-1,4-benzoquinone
25C, pH 6.5
additional information
additional information
-
stopped-flow and steady-state kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.21 - 4.2
1,2-naphthoquinone
0.207 - 15833
1,4-benzoquinone
0.195
1,4-Naphthoquinone
Homo sapiens
-
pH 7.4, 25C
520
2,3-dichloro-5,6-dicyano-1,4-benzoquinone
Kluyveromyces marxianus
Q8NKK9
25C, pH 6.5
0.068
2,3-dimethoxy-5-methyl-1,4-benzoquinone
Homo sapiens
-
pH 7.4, 25C
36.7
2,5-dimethyl-4-benzoquinone
Synechocystis sp.
-
pH 8.0, 25C, recombinant His-tagged enzyme
11
2-Hydroxy-1,4-naphthoquinone
Synechocystis sp.
-
pH 8.0, 25C, recombinant His-tagged enzyme
0.19
5-hydroxy-1,4-naphthoquinone
Homo sapiens
-
pH 7.4, 25C
0.01 - 4.2
9,10-phenanthrenequinone
9.4
anthraquinone-2-sulfonate
Synechocystis sp.
-
pH 8.0, 25C, recombinant His-tagged enzyme
5
coenzyme Q10
Synechocystis sp.
-
pH 8.0, 25C, recombinant His-tagged enzyme
35
dibromothymoquinone
Synechocystis sp.
-
pH 8.0, 25C, recombinant His-tagged enzyme
2.67 - 25
duroquinone
1600
hydroquinone
Kluyveromyces marxianus
Q8NKK9
25C, pH 6.5
0.212 - 26
menadione
360
phenyl-1,4-benzoquinone
Kluyveromyces marxianus
Q8NKK9
25C, pH 6.5
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
462
1,2-naphthoquinone
Saccharomyces cerevisiae
-
pH 7.0, temperature not specified in the publication
1907
0.06 - 1041
9,10-phenanthrenequinone
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
Cibacron blue F3GA
-
pH 7.4, 25C
0.057
NADP+
-
pH 7.4, 25C
0.0003
Procion red HE3B
-
pH 7.4, 25C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008 - 0.01
dicoumarol
Synechocystis sp.
-
with dichlorophenolindophenol, pH 8.0, 25C, recombinant His-tagged enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.000003
substrate (R,S)-camphorquinone, mutant Y55F, pH 6.0, 25C
0.00002
substrate (R,S)-camphorquinone, mutant Y55S, pH 6.0, 25C
0.0005
-
medium alone
0.0006
substrate acenaphthenequinone, mutant Y55F, pH 6.0, 25C; substrate acenaphthenequinone, mutant Y55S, pH 6.0, 25C
0.0007
-
TNFalpha and LPS inhibit the beta-naphthoflavone induced increase in activity
0.0012
-
in presence of beta-naphthoflavone
0.0016
substrate 9,10-phenanthrenenquinone, mutant Y55S, pH 6.0, 25C
0.0018
substrate 9,10-phenanthrenenquinone, mutant Y55F, pH 6.0, 25C
0.0025
substrate (R,S)-camphorquinone, wild-type, pH 6.0, 25C
0.0038
substrate acenaphthenequinone, wild-type, pH 6.0, 25C
0.0044
substrate 9,10-phenanthrenenquinone, wild-type, pH 6.0, 25C
1.097
-
activity of purified cytochrome b558 reconstituted with neutrophil membrane phospholipids, activation with arachidonic acid
1.258
-
activity of purified cytochrome b558 reconstituted with neutrophil membrane phospholipids, activation with sodiumdodecylsulfate
1067
-
pH 7.5, 30C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 7.5
-
-
7.4
-
assay at
8
-
assay at
9.1
calculation from nucleotide sequence
additional information
the pH dependency of 9,10-phenanthrenequinone reduction catalyzed by the wild-type enzyme is different to that observed for 3-ketosteroid reduction. The kcat value for 9,10-phenanthrenequinone reduction is pH-dependent with the maximal rate decreasing with increasing pH but reveals an ionizable group with a pKb of 8.90 that must be protonated for maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22
-
assay at room temperature
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
for genotyping
Manually annotated by BRENDA team
-
soleus, gastrocnemius, and quadriceps muscles, primary culture of cells
Manually annotated by BRENDA team
additional information
-
no activity in endothelial cells, membrane-enriched
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
NADPH oxidase complex consists of membrane and cytosolic subunits
Manually annotated by BRENDA team
-
CBR4 is a mitochondrial matrix protein, its N-terminal signal is not cleaved
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain K12)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30000 - 40000
-
ultracentrifugal analysis
42000
-
PAGE
60260
-
enzyme form DII, gel filtration
66070
-
enzyme form DI, gel filtration
84000
gel filtration
100000
-
gel filtration
additional information
-
enzyme displays three charge isomers with different relative mobilities
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
octamer
-
8 * 5100, SDS-PAGE
tetramer
additional information
-
NADPH oxidase complex consists of membrane and cytosolic subunits. The gp91phox and p22phox are integral membrane proteins that form a heterodimeric flavocytochrome b558, the catalytic core of the enzyme
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sitting drop vapour diffusion method. In addition to the oxidized and reduced enzyme form, the structures of the complexes with p-hydroxybenzaldehyde and p-nitrophenol, respectively are solved
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cytochrome b558 from neutrophils
-
native enzyme partially by membrane preparation
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cytosolic components p67-phox and p47-phox of the multicomponent NADPH oxidase
-
expression in Escherichia coli
expression of p47-phox and p67-phox in Sf9 cells
-
gene arsh, expression as N-terminallyy His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
overexpression of CBR4 in bovine endothelial cells reveals that the enzyme has a non-cleavable mitochondrial targeting signal
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
induction under different types of cellular stress, including ethanol and dimethylsulfoxide exposure and by reaching the stationary growth phase
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
P187S
-
Pro187Ser polymorphism in NQO1 has a limited role in the development of Tardive dyskinesia (a potentially irreversible side effect of antipsychotic medication treatment that occurs in approximately 25% of chronically treated schizophrenia patients)
D50N
less than 0.1% of wild-type activity
H117A
less than 0.1% of wild-type activity
K84M
complete loss of activity
K84R
complete loss of activity
Y55F
narrow substrate specificity, reduction of selected aromatic quinones and alpha-dicarbonyls. The activation energy for 9,10-phenanthrenequinone reduction is unchanged in Y55 mutants
Y55S
narrow substrate specificity, reduction of selected aromatic quinones and alpha-dicarbonyls. The activation energy for 9,10-phenanthrenequinone reduction is unchanged in Y55 mutants
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine