Information on EC 1.6.5.5 - NADPH:quinone reductase

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

EC NUMBER
COMMENTARY
1.6.5.5
-
RECOMMENDED NAME
GeneOntology No.
NADPH:quinone reductase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NADPH + H+ + 2 quinone = NADP+ + 2 semiquinone
show the reaction diagram
reaction with 9,10-phenanthrenequinone and NADPH proceeds through a ping-pong mechanism
-
NADPH + H+ + 2 quinone = NADP+ + 2 semiquinone
show the reaction diagram
reaction with 2,6-dichlorophenolindophenol and NADPH proceeds through a ping-pong mechanism
-
NADPH + H+ + 2 quinone = NADP+ + 2 semiquinone
show the reaction diagram
enzyme acts through a one-electron transfer process
-
NADPH + H+ + 2 quinone = NADP+ + 2 semiquinone
show the reaction diagram
ping pong reaction mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
NADPH:quinone oxidoreductase
A zinc enzyme, specific for NADPH. Catalyses the one-electron reduction of certain quinones, with the orthoquinones 1,2-naphthoquinone and 9,10-phenanthrenequinone being the best substrates [1]. Dicoumarol [cf. EC 1.6.5.2 NAD(P)H dehydrogenase (quinone)] and nitrofurantoin are competitive inhibitors with respect to the quinone substrate. The semiquinone free-radical product may be non-enzymically reduced to the hydroquinone or oxidized back to quinone in the presence of O2 [1]. In some mammals, the enzyme is abundant in the lens of the eye, where it is identified with the protein zeta-crystallin.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Dehydrogenase, reduced nicotinamide adenine dinucleotide (phosphate) (quinone)
-
-
-
-
DT-diaphorase
-
-
-
-
EC 1.6.99.2
-
-
related
-
Flavoprotein NAD(P)H:quinone reductase
-
-
-
-
Menadione oxidoreductase
-
-
-
-
Menadione reductase
-
-
-
-
NAD(P)H dehydrogenase
-
-
-
-
NAD(P)H dehydrogenase (quinone)
-
-
-
-
NAD(P)H menadione reductase
-
-
-
-
NAD(P)H quinone reductase
-
-
-
-
NAD(P)H-quinone dehydrogenase
-
-
-
-
NAD(P)H-quinone oxidoreductase
-
-
-
-
NAD(P)H-quinone reductase
-
-
-
-
NAD(P)H:(quinone-acceptor) oxidoreductase
-
-
-
-
NAD(P)H:menadione oxidoreductase
-
-
-
-
NAD(P)H:paraquat diaphorase
-
-
-
-
NADH-menadione reductase
-
-
-
-
NADH-menaquinone reductase
-
-
-
-
NADH:quinone reductase
-
-
-
-
NADPH DT-diaphorase
-
-
-
-
NADPH quinone acceptor oxidoreductase
-
-
NADPH-dependent quinone reductase
-
-
NADPH:azodicarbonyl/quinone reductase
-
-
NADPH:quinone oxidoreductase
-
-
-
-
NADPH:quinone oxidoreductase
-
-
NADPH:quinone reductase
-
-
-
-
Naphthoquinone reductase
-
-
-
-
old yellow enzyme
-
-
p-Benzoquinone reductase
-
-
-
-
P36
-
-
-
-
Phylloquinone reductase
-
-
-
-
Quinone reductase
-
-
-
-
Reduced NAD(P)H dehydrogenase
-
-
-
-
TmQR1
Q56D13
-
Viologen accepting pyridine nucleotide oxidoreductase
-
-
-
-
Vitamin K reductase
-
-
-
-
zeta-Crystallin
-
-
-
-
zeta-Crystallin
-
-
zeta-Crystallin
Cavia porcellus 13/N
-
-
-
zeta-Crystallin
-
-
zeta-Crystallin
Q08257
-
zeta-Crystallin
-
-
zeta-Crystallin
-
-
zeta-Crystallin
P38230
-
Zeta-crystallin homolog protein
-
-
-
-
zeta-Crystallin/NADPH:quinone oxidoreductase
-
-
-
-
zeta-Crystallin/quinone reductase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9032-20-6
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
zeta crystallin shows minimal NADPH:quinone reductase activity
-
-
Manually annotated by BRENDA team
strain 13/N
-
-
Manually annotated by BRENDA team
Cavia porcellus 13/N
strain 13/N
-
-
Manually annotated by BRENDA team
pv. tomato DC3000
-
-
Manually annotated by BRENDA team
gene arsh, encoded in the arsenic resistance operon
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
-
ArsH plays a role in the response to oxidative stress caused by arsenite
additional information
-
in silico structural model of ArsH reconstituted with FMN, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
1,2-naphthoquinone + NADPH
1,2-naphthoquinol + NADP+
show the reaction diagram
-
-
-
-
-
1,2-naphthoquinone + NADPH
1,2-naphthoquinol + NADP+
show the reaction diagram
-
-
-
-
-
1,2-naphthoquinone + NADPH + H+
1,2-naphthosemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
1,2-naphthoquinone + NADPH + H+
? + NADP+
show the reaction diagram
-
the activity with 9,10-phenanthrenequinone and with 1,2-naphthoquinone is equal
-
-
?
1,4-benzoquinone + NADPH
1,4-benzoquinol + NADP+
show the reaction diagram
-
-
-
-
-
1,4-benzoquinone + NADPH
1,4-benzoquinol + NADP+
show the reaction diagram
-
15.3% of the activity with 1,2-naphthoquinone
-
-
-
1,4-benzoquinone + NADPH + H+
1,4-benzosemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
1,4-naphthoquinone + NADPH
1,4-naphthoquinol + NADP+
show the reaction diagram
-
-
-
-
-
1,4-naphthoquinone + NADPH
1,4-naphthoquinol + NADP+
show the reaction diagram
-
-
-
-
-
1,4-naphthoquinone + NADPH
1,4-naphthoquinol + NADP+
show the reaction diagram
-
2.6% of the activity with 1,2-naphthoquinone
-
-
-
1,4-naphthoquinone + NADPH + H+
1,4-naphthosemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2 1,2-naphthoquinone + NADPH + H+
2 1,2-naphthosemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2 1,2-naphthoquinone + NADPH + H+
? + NADP+
show the reaction diagram
-
the activity with 9,10-phenanthrenequinone and with 1,2-naphthoquinone is equal
-
-
?
2 1,4-benzoquinone + NADPH + H+
2 1,4-benzosemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2 1,4-benzoquinone + NADPH + H+
? + NADP+
show the reaction diagram
-
weak activity
-
-
?
2 1,4-naphthosemiquinone + NADPH + H+
2 1,4-naphthosemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2 5-hydroxy-1,4-naphthoquinone + NADPH + H+
2 5-hydroxy-1,4-naphthosemiquinone + NADP+
show the reaction diagram
-
i.e. juglone. Production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2 5-hydroxy-2-methyl-1,4-naphthoquinone + NADPH + H+
5-hydroxy-2-methyl-1,4-naphthoquinone + NADP+
show the reaction diagram
-
i.e. plumbagin. Production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2 9,10-phenanthrenequinone + NADPH + H+
2 9,10-phenanthrenesemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2 9,10-phenanthrenequinone + NADPH + H+
2 9,10-phenanthrenesemiquinone + NADP+
show the reaction diagram
-
very strong reduction activity towards large substrates such as 9,10-phenanthrenequinone. The zeta-crystallin-like quinone oxidoreductase catalyzes one-electron reduction of certain quinones to generate semiquinone
-
-
?
2 9,10-phenanthrenequinone + NADPH + H+
? + NADP+
show the reaction diagram
-
70% of the activity with 9,10-phenanthrenequinone
-
-
?
2 decyl-plastoquinone + NADPH + H+
2 decyl-plastosemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
2-hexenal + NADPH
hexanal + NADP+
show the reaction diagram
-
-
-
-
?
2-nonenal + NADPH
nonanal + NADP+
show the reaction diagram
-
-
-
-
?
2-pentenal + NADPH
pentanal + NADP+
show the reaction diagram
-
-
-
-
?
3-buten-2-one + NADPH
2-butanone + NADP+
show the reaction diagram
-
-
-
-
?
3-nonen-2-one + NADPH
2-nonanone + NADP+
show the reaction diagram
-
-
-
-
?
3-penten-2-one + NADPH
2-pentanone + NADP+
show the reaction diagram
-
-
-
-
?
4-hydroxy-2-hexenal + NADPH
4-hydroxy-hexanal + NADP+
show the reaction diagram
-
-
-
-
?
4-hydroxy-2-nonenal + NADPH
4-hydroxy-nonanal + NADP+
show the reaction diagram
-
-
-
-
?
5-hydroxy-1,4-naphthoquinone + NADPH
5-hydroxy-1,4-naphthoquinol + NADP+
show the reaction diagram
-
-
-
-
-
5-hydroxy-1,4-naphthoquinone + NADPH
5-hydroxy-1,4-naphthoquinol + NADP+
show the reaction diagram
-
i.e. juglone, 12.5% of the activity with 1,2-naphthoquinone
-
-
-
5-hydroxy-1,4-naphthoquinone + NADPH + H+
5-hydroxy-1,4-naphthosemiquinone + NADP+
show the reaction diagram
-
i.e. juglone. Production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
5-hydroxy-1,4-naphthoquinone + NADPH + H+
?
show the reaction diagram
-
i.e. juglone
-
-
?
5-hydroxy-2-methyl-1,4-naphthoquinone + NADPH
5-hydroxy-2-methyl-1,4-naphthoquinol + NADP+
show the reaction diagram
-
i.e. plumbagin, 0.9% of the activity with 1,2-naphthoquinone
-
-
-
5-hydroxy-2-methyl-1,4-naphthoquinone + NADPH + H+
5-hydroxy-2-methyl-1,4-naphthosemiquinone + NADP+
show the reaction diagram
-
i.e. plumbagin. Production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
9,10-phenanthrenequinone + NADPH
9,10-phenanthrenequinol + NADP+
show the reaction diagram
-
-
-
-
-
9,10-phenanthrenequinone + NADPH
9,10-phenanthrenequinol + NADP+
show the reaction diagram
-
-
-
-
-
9,10-phenanthrenequinone + NADPH
9,10-phenanthrenequinol + NADP+
show the reaction diagram
-
best substrate
-
-
-
9,10-phenanthrenequinone + NADPH
9,10-phenanthrenequinol + NADP+
show the reaction diagram
-
50% of the activity with 1,2-naphthoquinone
-
-
-
9,10-phenanthrenequinone + NADPH + H+
9,10-phenanthrenequinol + NADP+
show the reaction diagram
Q7A492
one-electron reduction mechanism. Concomitantly with NADPH consumption, generation of superoxide is observed
-
-
?
9,10-phenanthrenequinone + NADPH + H+
9,10-phenanthrenesemiquinone + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
9,10-phenanthrenequinone + NADPH + H+
? + NADP+
show the reaction diagram
-
the activity with 9,10-phenanthrenequinone and with 1,2-naphthoquinone is equal
-
-
?
dichlorophenolindophenol + NADPH + H+
reduced dichlorophenolindophenol + NADP+
show the reaction diagram
-
-
-
-
?
dichlorophenolindophenol + NADPH + H+
reduced dichlorophenolindophenol + NADP+
show the reaction diagram
-
production of semiquinone by univalent catalysts is detectable by the reduction of ferricytochrome c by the semiquinone to ferrocytochrome c
-
-
?
ferricytochrome + NADPH + H+
ferrocytochrome + NADPH
show the reaction diagram
-
-
-
-
?
menadione + NADPH + H+
menadiol + NADP+
show the reaction diagram
Q7A492
-
-
-
?
menadione + NADPH + H+
menadiol + NADP+
show the reaction diagram
-
-
under aerobic conditions, menadiol is readily oxidized to menadione by two 1-electron steps producing the semiquinone and the parent quinone with concomitant production of superoxide anion, which leads to generation of hydroxyl radicals
-
?
NADPH + H+ + 2 2,5-dimethyl-4-benzoquinone
NADP+ + 2 2,5-dimethyl-4-benzosemiquinone
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2 2-hydroxy-1,4-naphthoquinone
NADP+ + 2 2-hydroxy-1,4-naphthosemiquinone
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2 anthraquinone-2-sulfonate
NADP+ + ?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2 coenzyme Q10
NADP+ + ?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2 dibromothymoquinone
NADP+ + 2 dibromothymosemiquinone
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2 duroquinone
NADP+ + 2 durosemiquinone
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2 menadione
NADP+ + ?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + 2 quinone
NADP+ + 2 semiquinone
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+ + komaroviquinone
NADP+ + ?
show the reaction diagram
-
reduction of komaroviquinone to its semiquinone radical. Antichagasic activity of komaroviquinone is due to generation of reactive oxygen species catalyzed by Trypanosoma cruzi old yellow enzyme
-
-
?
NADPH + H+ + menadione
NADP+ + ?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + nifurtimox
NADP+ + ?
show the reaction diagram
-
-
-
-
?
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
-
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
-
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
3.8% of the activity with 1,2-naphthoquinone
-
-
-
propenal + NADPH
propanal + NADP+
show the reaction diagram
-
-
-
-
?
methyl-1,4-benzoquinone + NADPH
methyl-1,4-benzoquinol + NADP+
show the reaction diagram
-
20.6% of the activity with 1,2-naphthoquinone
-
-
-
additional information
?
-
-
no activity with menadione and 9,10-anthraquinone
-
-
-
additional information
?
-
-
inactive with: menadione, ubiquinone, 9,10-anthraquinone, vitamin K1, vitamin K2
-
-
-
additional information
?
-
-
although in the lens the enzyme is considered to be a crystallin, or lens structural protein, because of its high abundance its enzymatic activity and expression at catalytic levels in other tissues of various species suggest that it has a fundamental physiological role outside the lens, perhaps in the detoxification of xenobiotics
-
-
-
additional information
?
-
-
the human and yeast enzymes specifically bind to adenine-uracil rich elements (ARE) in RNA, indicating that both enzymes are ARE-binding proteins and that this property has been conserved in zeta-crystallins throughout evolution. This supports a role for zeta-crystallins as trans-acting factors that could regulate the turnover of certain mRNAs
-
-
-
additional information
?
-
-
enzyme reduces ortho-quinones in the presence of NADPH but is not active with 2-alkenals
-
-
-
additional information
?
-
-
no activity with: phylloquinone (vitamin K1), menaquinone (vitamin K2), menadione (vitamin K3) and ferricyanide. Preference for o-quinones over p-quinones, and the inability to recognize menadione and ferricyanide as substrates, clearly distinguishe P1-ZCr and guinea-pig ZCr from the flavin-containing NAD(P)H-quinone oxidoreductases in plants and animals. P1-ZCr also catalyzed the divalent reduction of diamide to 1,2-bis(N,N-dimethylcarbamoyl)hydrazine, with a kcat comparable with that for quinones. Two other azodicarbonyl compounds also served as substrates of P1-ZCr. Guinea-pig ZCr, however, did not catalyze the azodicarbonyl reduction. Hence, plant ZCr is distinct from mammalian ZCr, and can be referred to as NADPH:azodicarbonyl/quinone reductase. The quinone-reducing reaction is accompanied by radical chain reactions to produce superoxide radicals, while the azodicarbonyl reducing reaction is not
-
-
-
additional information
?
-
-
no activity with: phylloquinone (vitamin K1), menaquinone (vitamin K2), menadione (vitamin K3), ferricytochrome and ferricyanide. Preference for o-quinones over p-quinones, and the inability to recognize menadione and ferricyanide as substrates, clearly distinguishe Arabidopsis thaliana P1-ZCr and guinea-pig ZCr from the flavin-containing NAD(P)H-quinone oxidoreductases in plants and animals
-
-
-
additional information
?
-
Q56D13
QR1 catalyzes the univalent reduction of quinones to semiquinone radicals
-
-
-
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
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NADPH + H+ + 2 quinone
NADP+ + 2 semiquinone
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
although in the lens the enzyme is considered to be a crystallin, or lens structural protein, because of its high abundance its enzymatic activity and expression at catalytic levels in other tissues of various species suggest that it has a fundamental physiological role outside the lens, perhaps in the detoxification of xenobiotics
-
-
-
additional information
?
-
-
the human and yeast enzymes specifically bind to adenine-uracil rich elements (ARE) in RNA, indicating that both enzymes are ARE-binding proteins and that this property has been conserved in zeta-crystallins throughout evolution. This supports a role for zeta-crystallins as trans-acting factors that could regulate the turnover of certain mRNAs
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
-
specific for
NADPH
Q8L3C8
NADPH is located in the cleft between domains I and II. The adenine ring is sandwiched between the main chains of Ala220 and Glu221 and the side chain of Arg292. Ala220 and Glu221 are disordered in apo-QOR
NADPH
-
NADPH binding causes conformational changes in the structure of the enzyme
NADPH
-
completely specific for NADPH as cofactor
NADPH
-
NADPH, but not NADH, competitively prevents binding of zeta-crystallin to RNA, suggesting that the cofactor-binding site is involved in RNA binding
NADPH
P38230
interference of NADPH on Zta1p binding to RNA is much lower than that of NADPH on human zeta-crystallin, consistent with a weaker binding of NADPH to the yeast enzyme
NADPH
-
specificity to NADPH, as judged by kcat/Km, is more than 1000fold higher than that to NADH
NADPH
-
-
NADPH
Q7A492
-
NADPH
-
-
FMN
-
in silico structural model of ArsH reconstituted with FMN, overview
additional information
Q7A492
no cofactor: NADH. Sequence does not contain a flavin-binding motif
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,3-Dimercaptopropanol
-
-
2,5-Dichloro-3,6-dihydroxy-1,4-benzoquinone
-
i.e. chloranilic acid, noncompetitive with respect to both NADPH and 9,10-phenanthrenequinone
4-chloromercuribenzoate
-
both NADPH and NADP1 suppress the inhibition, but NADH does not
4-Hydroxycoumarin
-
reversible time-independent inhibition. Only dicoumarol, 4-hydroxycoumarin and warfarin inhibit in micromolar ranges. 7-Hydroxy-4-methylcoumarin is ineffective. Competitive inhibition with respect to 2,6-dichlorophenolindophenol, uncompetitive with respect to NADPH. Phenolic hydroxyl group at the C-4 position in the coumarin skeleton is important for the maximal inhibition. Sequence of potency for the inhibitors in descending order: dicoumarol, 4-hydroxycoumarin, warfarin, coumarin
5,5'-dithiobis(2-nitrobenzoate)
-
-
5,5'-dithiobis(2-nitrobenzoate)
-
inactivation is caused by a modification of one Cys per subunit, reactivation by dithiothreitol or KCN. NADPH partially protects from inactivation, 9,10-phenanthrenequinone enhances the modification
5,5'-dithiobis(2-nitrobenzoate)
-
-
ADP
-
10% inhibition at 0.2 mM
Cibacron blue 3GA
-
-
Cibacron blue 3GA
-
inhibits the reaction with NADPH and 9,10-phenanthrenequinone. Linear mixed type inhibition with respect to NADPH and noncompetitive with respect to 9,10-phenanthrenequinone
coumarin
-
reversible time-independent inhibition. Only dicoumarol, 4-hydroxycoumarin and warfarin inhibit in micromolar ranges. 7-Hydroxy-4-methylcoumarin is ineffective. Competitive inhibition with respect to 2,6-dichlorophenolindophenol, uncompetitive with respect to NADPH. Phenolic hydroxyl group at the C-4 position in the coumarin skeleton is important for the maximal inhibition. Sequence of potency for the inhibitors in descending order: dicoumarol, 4-hydroxycoumarin, warfarin, coumarin
Cu2+
-
25% inhibition at 1 mM
dicoumarol
-
-
dicoumarol
-
competitive with respect to 2,6-dichlorophenol-indophenol, uncompetitive with respect to NADPH
dicoumarol
-
reversible time-independent inhibition. Only dicoumarol, 4-hydroxycoumarin and warfarin inhibit in micromolar ranges. 7-Hydroxy-4-methylcoumarin is ineffective. Competitive inhibition with respect to 2,6-dichlorophenolindophenol, uncompetitive with respect to NADPH. Phenolic hydroxyl group at the C-4 position in the coumarin skeleton is important for the maximal inhibition.Sequence of potency for the inhibitors in descending order: dicoumarol, 4-hydroxycoumarin, warfarin, coumarin
dicoumarol
-
-
dicoumarol
-
mixed-type inhibition against NADPH
dicoumarol
-
presence of dicoumarol decreases the production of hydroxyl radical and attenuates DNA strand-breaks in MCF-7 cells treated with menadione
dithiothreitol
-
inhibition is completely prevented by preincubation with 9,10-phenanthrenequinone but not by NADPH
dithiothreitol
-
strong competitive inhibition with respect to 9,10-phenanthrenequinone
FAD
-
60% inhibition at 0.2 mM
FMN
-
40% inhibition at 0.2 mM
N-ethylmaleimide
-
both NADPH and NADP1 suppress the inhibition, but NADH does not
NAD+
-
5% inhibition at 0.2 mM
NADP+
-
mixed-type inhibition with respect to NADPH, competitive with respect to 9,10-phenanthrenequinone
NADP+
-
can act as a competitive inhibitor for NADPH binding at the active site of an enzyme
Nitrofurantoin
-
-
Nitrofurantoin
-
uncompetitive against NADPH
o-phthalaldehyde
-
-
p-Chloromercuriphenylsulfonate
-
-
pyridoxal-5'-phosphate
-
inactivation follows pseudo-first-order kinetics. NADPH protects against inactivation, 9,10-phenanthrenequinone does not protect. Inhibition is uncompetitive with NADPH and non-competitive with respect to 9,10-phenanthrenequinone
Warfarin
-
reversible time-independent inhibition. Only dicoumarol, 4-hydroxycoumarin and warfarin inhibit in micromolar ranges. 7-Hydroxy-4-methylcoumarin is ineffective. Competitive inhibition with respect to 2,6-dichlorophenolindophenol, uncompetitive with respect to NADPH. Phenolic hydroxyl group at the C-4 position in the coumarin skeleton is important for the maximal inhibition. Sequence of potency for the inhibitors in descending order: dicoumarol, 4-hydroxycoumarin, warfarin, coumarin
Warfarin
-
-
Zn2+
-
25% inhibition at 1 mM
menadione
-
-
additional information
-
no inactivation by 0.5 mM iodoacetate
-
additional information
-
inhibition studies suggest that an essential disulfide-bridge is present at the binding site of zeta-crystallin
-
additional information
-
the results of the inhibition studies suggest that an essential Lys is located in the vicinity of the NADPH binding site
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0024
1,2-naphthoquinone
-
-
0.009
1,2-naphthoquinone
-
pH 7.5
0.029
1,2-naphthoquinone
-
pH 7.5
0.065
1,4-benzoquinone
-
-
0.143
1,4-benzoquinone
-
-
0.143
1,4-benzoquinone
-
pH 7.5
0.152
1,4-benzoquinone
-
pH 7.5
0.26
1,4-Naphthoquinone
-
-
0.0013
2,5-dimethyl-4-benzoquinone
-
pH 7.5, 10C
-
0.013
2,6-dichlorophenolindophenol
-
-
0.0153
2,6-dichlorophenolindophenol
-
-
0.13
2-hexenal
-
pH 7, 25C, mutant T53F
5.45
2-hexenal
-
pH 7, 25C, wild-type
6.12
2-hexenal
-
pH 7, 25C, mutant T59F
0.0237
2-Hydroxy-1,4-naphthoquinone
-
pH 7.5, 10C
0.482
2-nonenal
-
pH 7, 25C, wild-type
8.6
2-pentenal
-
pH 7, 25C, wild-type
-
0.035
3-buten-2-one
-
pH 7, 25C, wild-type
0.06
3-buten-2-one
-
pH 7, 25C, mutant T59F
0.13
3-buten-2-one
-
pH 7, 25C, mutant T53F
0.05
3-nonen-2-one
-
pH 7, 25C, mutant T53F
0.94
3-nonen-2-one
-
pH 7, 25C, wild-type
0.06
3-penten-2-one
-
pH 7, 25C, mutant T53F
0.535
3-penten-2-one
-
pH 7, 25C, wild-type
0.08
4-hydroxy-2-hexenal
-
pH 7, 25C, mutant T53F
0.13
4-hydroxy-2-hexenal
-
pH 7, 25C, wild-type
1.26
4-hydroxy-2-hexenal
-
pH 7, 25C, mutant T59F
0.55
4-hydroxy-2-nonenal
-
pH 7, 25C, wild-type
0.011
5-hydroxy-1,4-naphthoquinone
-
pH 7.5
0.027
5-hydroxy-1,4-naphthoquinone
-
-
0.027
5-hydroxy-1,4-naphthoquinone
-
pH 7.5
0.00065
9,10-phenanthrenequinone
-
pH 7.5
0.0015
9,10-phenanthrenequinone
-
pH 7.5
0.004
9,10-phenanthrenequinone
-
pH 7.5
0.01
9,10-phenanthrenequinone
-
-
0.013
9,10-phenanthrenequinone
-
pH 7.5
0.017
9,10-phenanthrenequinone
-
-
0.0491
9,10-phenanthrenequinone
Q7A492
pH 7.5, 25C
0.0345
anthraquinone-2-sulfonate
-
pH 7.5, 10C
0.0119
coenzyme Q10
-
pH 7.5, 10C
0.025
decyl-plastoquinone
-
pH 7.5
0.0012
dibromothymoquinone
-
pH 7.5, 10C
0.0028
duroquinone
-
pH 7.5, 10C
0.02
Ferricytochrome
-
pH 7.5
0.03
komaroviquinone
-
-
0.0057
menadione
-
pH 7.5, 10C
0.0025
NADPH
-
pH 7.5, cosubstrate: 9,10-phenanthrenequinone
0.005
NADPH
-
-
0.005
NADPH
-
pH 7.5
0.005
NADPH
-
pH 7, 25C, wild-type
0.0069
NADPH
-
-
0.007
NADPH
-
-
0.015
NADPH
-
pH 7, 25C, mutant T59F
0.0315
NADPH
-
pH 7.5, 10C
0.06
NADPH
-
pH 7, 25C, mutant T53F
0.07
NADPH
-
pH 7.5
0.013
nifurtimox
-
-
0.86
propenal
-
pH 7, 25C, mutant T59F
1.45
propenal
-
pH 7, 25C, wild-type
2.3
propenal
-
pH 7, 25C, mutant T53F
0.019
menadione
-
-
additional information
additional information
-
stopped-flow and laser-flash photolysis kinetic analyses, steady-state kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.8
1,2-naphthoquinone
-
pH 7.5
4.17
1,2-naphthoquinone
-
pH 7.5
39
1,2-naphthoquinone
-
pH 7.5
54
1,2-naphthoquinone
-
pH 7.5
3.4
1,4-benzoquinone
-
-
5.9
1,4-benzoquinone
-
pH 7.5
12
1,4-benzoquinone
-
pH 7.5
1
1,4-Naphthoquinone
-
pH 7.5
3
1,4-Naphthoquinone
-
pH 7.5
36.7
2,5-dimethyl-4-benzoquinone
-
pH 7.5, 10C
-
0.28
2-hexenal
-
pH 7, 25C, wild-type
0.36
2-hexenal
-
pH 7, 25C, mutant T59F
73.27
2-hexenal
-
pH 7, 25C, mutant T53F
11
2-Hydroxy-1,4-naphthoquinone
-
pH 7.5, 10C
0.11
2-nonenal
-
pH 7, 25C, wild-type
0.2
2-pentenal
-
pH 7, 25C, wild-type
-
0.16
3-buten-2-one
-
pH 7, 25C, wild-type
0.28
3-buten-2-one
-
pH 7, 25C, mutant T59F
0.97
3-buten-2-one
-
pH 7, 25C, mutant T53F
0.21
3-nonen-2-one
-
pH 7, 25C, wild-type
3.11
3-nonen-2-one
-
pH 7, 25C, mutant T53F
0.2
3-penten-2-one
-
pH 7, 25C, wild-type
2.66
3-penten-2-one
-
pH 7, 25C, mutant T53F
1.33
4-hydroxy-2-hexenal
-
pH 7, 25C, wild-type
2.16
4-hydroxy-2-hexenal
-
pH 7, 25C, mutant T59F
3.67
4-hydroxy-2-hexenal
-
pH 7, 25C, mutant T53F
1.15
4-hydroxy-2-nonenal
-
pH 7, 25C, wild-type
1.9
5-hydroxy-1,4-naphthoquinone
-
pH 7.5
2.6
5-hydroxy-1,4-naphthoquinone
-
-
4.9
5-hydroxy-1,4-naphthoquinone
-
pH 7.5
0.37
5-Hydroxy-2-methyl-1,4-naphthoquinone
-
pH 7.5
3.8
5-hydroxy-2-methyl-1,4-naphtoquinone
-
pH 7.5
-
2.2
9,10-phenanthrenequinone
-
pH 7.5
4.17
9,10-phenanthrenequinone
-
pH 7.5
10
9,10-phenanthrenequinone
-
-
19
9,10-phenanthrenequinone
-
pH 7.5
98
9,10-phenanthrenequinone
-
pH 7.5
9.4
anthraquinone-2-sulfonate
-
pH 7.5, 10C
5
coenzyme Q10
-
pH 7.5, 10C
0.1
decyl-plastoquinone
-
pH 7.5
35
dibromothymoquinone
-
pH 7.5, 10C
1.5
dichlorophenolindophenol
-
pH 7.5
7.5
dichlorophenolindophenol
-
pH 7.5
25
duroquinone
-
pH 7.5, 10C
0.03
Ferricytochrome
-
pH 7.5
26
menadione
-
pH 7.5, 10C
1.25
propenal
-
pH 7, 25C, mutant T59F
1.66
propenal
-
pH 7, 25C, wild-type
39.74
propenal
-
pH 7, 25C, mutant T53F
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0016
2-hexenal
-
pH 7, 25C, mutant T53F
6215
0.051
2-hexenal
-
pH 7, 25C, wild-type
6215
0.06
2-hexenal
-
pH 7, 25C, mutant T59F
6215
0.23
2-nonenal
-
pH 7, 25C, wild-type
5769
0.023
2-pentenal
-
pH 7, 25C, wild-type
0
0.13
3-buten-2-one
-
pH 7, 25C, mutant T53F
2904
4.6
3-buten-2-one
-
pH 7, 25C, mutant T59F
2904
4.8
3-buten-2-one
-
pH 7, 25C, wild-type
2904
0.016
3-nonen-2-one
-
pH 7, 25C, mutant T53F
6728
0.23
3-nonen-2-one
-
pH 7, 25C, wild-type
6728
0.025
3-penten-2-one
-
pH 7, 25C, mutant T53F
4103
0.36
3-penten-2-one
-
pH 7, 25C, wild-type
4103
0.023
4-hydroxy-2-hexenal
-
pH 7, 25C, mutant T53F
4640
1.66
4-hydroxy-2-hexenal
-
pH 7, 25C, mutant T59F
4640
10.21
4-hydroxy-2-hexenal
-
pH 7, 25C, wild-type
4640
2.1
4-hydroxy-2-nonenal
-
pH 7, 25C, wild-type
1426
0.058
propenal
-
pH 7, 25C, mutant T53F
4108
1.16
propenal
-
pH 7, 25C, wild-type
4108
1.5
propenal
-
pH 7, 25C, mutant T59F
4108
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
14.8
Q7A492
substrate menadione, pH 7.5, 25C
311
Q7A492
substrate 9,10-phenanthrenequinone, pH 7.5, 25C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 8
-
assay at
7.8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 10
-
pH 4.5: about 60% of maximal activity, pH 10: about 50% of maximal activity
7.5 - 9.2
-
half-maximal activity at pH 7.5 and pH 9.2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10 - 25
-
assay at
25
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
20 - 60
-
about 60% of maximal activity at 20C and at 60C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.2
Q7A492
calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
the enzyme is expressed throughout the Trypanosoma cruzi life cycle
Manually annotated by BRENDA team
Q56D13
the gene for QR1 is isolated from an expressed sequence tag collection derived from the epidermis of a diploid Triticum monococcum L. 24 h after inoculation with the powdery mildew fungus Blumeria graminis EO Speer f. sp. tritici Em. Marchal. TmQR1 is repressed while TmQR2 is induced in the epidermis during powdery mildew infection
Manually annotated by BRENDA team
-
the enzyme is expressed throughout the Trypanosoma cruzi life cycle
Manually annotated by BRENDA team
-
the concentration of zeta crystallin for the cataract phenotype is approximately half that present in tissue from normal control animals
Manually annotated by BRENDA team
Cavia porcellus 13/N
-
the concentration of zeta crystallin for the cataract phenotype is approximately half that present in tissue from normal control animals
-
Manually annotated by BRENDA team
-
in animals homozygous for the cataract phenotype the normal zeta-crystallin polypeptide is absent from the lens
Manually annotated by BRENDA team
Cavia porcellus 13/N
-
in animals homozygous for the cataract phenotype the normal zeta-crystallin polypeptide is absent from the lens
-
Manually annotated by BRENDA team
-
the concentration of zeta crystallin for the cataract phenotype is approximately half that present in tissue from normal control animals
Manually annotated by BRENDA team
Cavia porcellus 13/N
-
the concentration of zeta crystallin for the cataract phenotype is approximately half that present in tissue from normal control animals
-
Manually annotated by BRENDA team
-
the enzyme is expressed throughout the Trypanosoma cruzi life cycle
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
P38230
localizes in both cytoplasm and nucleus
Manually annotated by BRENDA team
P38230
localizes in both cytoplasm and nucleus
Manually annotated by BRENDA team
-
it is possible that Arabidopsis P1-ZCr functions as a quinone reductase in vivo. Possible substrate quinones are not abundant in the cytosol, but under severe stress the quinones might be liberated from the cell compartments where they are normally sequestered, as exemplified by the release of polyphenols from vacuoles and polyphenol oxidase from thylakoid lumen upon the disruption of cells. Quinone reduction would not lead to the radical chain reaction, because superoxide dismutase is ubiquitous in cells
Manually annotated by BRENDA team
additional information
-
not in nucleus
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
Coxiella burnetii (strain RSA 493 / Nine Mile phase I)
Pseudomonas syringae pv. tomato (strain DC3000)
Pseudomonas syringae pv. tomato (strain DC3000)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
Saccharomyces cerevisiae (strain ATCC 204508 / S288c)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
14000
-
gel filtration
697208
70000
-
gel filtration
697208
83200
-
gel filtration
697701
108000
-
gel filtration
724333
140000
-
gel filtration
14081
140000
-
gel filtration
14085
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
-
2 * 38700, recombinant P1-ZCr is a noncovalent dimer, SDS-PAGE
dimer
-
PtoQOR forms as a homologous dimer, each monomer containing two domains
dimer
-
gel filtration, 3 M NaCl
homodimer
-
2 * 36000, SDS-PAGE
homotetramer
-
4 * 36000, SDS-PAGE
homotetramer
-
gel filtration, 0.3 M NaCl
multimer
Q7A492
x * 36300, calculated and co-purification results
tetramer
-
4 * 35000, SDS-PAGE
tetramer
-
4 * 35000, SDS-PAGE
tetramer
-
4 * 25900, SDS-PAGE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystallographic structure of human zeta-crystallin is reported. Enzyme shows a tetrameric structure
-
crystal structures of zeta-crystallin-like quinone oxidoreductase and its complexes with NADPH determined at 2.4 and 2.01 A resolution
-
native enzyme and its complex with NADPH at 2.3 A and 2.8 A resolution. QOR forms a homodimer in the crystal by interaction of the betaF-strands in domain II, forming a large beta-sheet that crosses the dimer interface. NADPH is located between the two domains in the QOR-NADPH complex. The disordered segment involved in the coenzyme binding of apo-QOR becomes ordered upon NADPH binding. The segment covers an NADPH-binding cleft and may serve as a lid. The 2'-phosphate group of the adenine of NADPH is surrounded by polar and positively charged residues in QOR, suggesting that QOR binds NADPH more readily than NADH. The putative substrate-binding site of QOR, is largely blocked by nearby residues
Q8L3C8
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45
-
10 min, 65% loss of activity
14077
51
-
10 min, complete loss of activity
14077
80
Q8L3C8
thermal denaturation
655855
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
NADPH protects against inactivation caused by heat, NEM or H2O2
-
very stable to freezing
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, 5 months, stable
-
4C, stable for at least 1 month
-
-20C, less than 10% loss of activity after 4-6 weeks
-
4C, 1 week, complete inactivation of purified enzyme
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
using Ni-NTA chromatography
-
the quinone oxidoreductase activity of purified his-tagged recombinant mouse zeta-crystallin is comparable to that of purified native guinea pig lens zeta-crystallin, and to that of recombinant guinea pig zeta-crystallin. The method permits production of substantial amounts of recombinant zeta-crystallin for conducting studies on the biological role of this protein
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
-
expressed in Escherichia coli as a His-tagged fusion protein
-
expression in Escherichia coli
-
expression of His-tagged enzyme in Escherichia coli
-
expression in Escherichia coli
-
expression in Escherichia coli
Q7A492
expression in Escherichia coli, expression of TmQR1 is lethal to the cells, it is not possible to purify enough protein for further analysis
Q56D13
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
induced in presence of 9,10-phenanthrenequinone and by oxidative stress
Q7A492
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
T53F
-
Tyr53Phe mutant displays a large increase in Km values for all substrates and the cofactor, but mainly towards 3-buten-2-one and propenal with a 30fold increase. For 3-penten-2-one, 3-nonen-2-one, 2-hexenal and 4-hydroxy-2-hexenal mutant also shows a decrease in kcat
T59F
-
Tyr59Phe mutant exhibits almost the same kinetic parameter values as the wild-type enzyme for 2-alkenals,while the Km is increased for 4-hydroxy-2-hexenal
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
QAO does not possess a protective role in menadione-induced free radical production and DNA damage in human cancer cells. Under aerobic conditions, menadiol produced by QAR is readily oxidized to menadione by two 1-electron steps producing the semiquinone and the parent quinone with concomitant production of superoxide anion, which leads to generation of hydroxyl radicals