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Information on EC 1.6.5.5 - NADPH:quinone reductase and Organism(s) Homo sapiens and UniProt Accession Q08257
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1.6.5.5 NADPH:quinone reductaseIUBMB Comments
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 . 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 . In some mammals, the enzyme is abundant in the lens of the eye, where it is identified with the protein zeta-crystallin.
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Word Map
- 1.6.5.5
-
1.6.99.2
- flavin
- lens
- fmn
- flavoproteins
-
two-electron
- dicumarol
-
nadph:quinone-acceptor
- hydroquinone
- semiquinone
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bioreductive
- camel
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pentaerythritol
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tetranitrate
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nadph-quinone
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taxon-specific
- 2-methyl-1,4-naphthoquinone
- 5-aziridin-1-yl-2,4-dinitrobenzamide
- morphinone
-
1.6.2.4
- 2,4,6-trinitrotoluene
- eo9
- p-hydroxybenzaldehyde
- 9,10-phenanthrenequinone
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explosives
-
nitroaromatic
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alpha,beta-unsaturated
- pastorianus
-
single-electron
-
enones
-
2.5.1.18
- environmental protection
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
zeta-crystallin, old yellow enzyme, vat-1, nadph:quinone oxidoreductase, nad(p)h:menadione oxidoreductase, tcoye, nad(p)h:(quinone-acceptor) oxidoreductase, nad(p)h-quinone reductase, zta1p, p1-zcr, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Dehydrogenase, reduced nicotinamide adenine dinucleotide (phosphate) (quinone)
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DT-diaphorase
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Flavoprotein NAD(P)H:quinone reductase
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Menadione oxidoreductase
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Menadione reductase
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NAD(P)H dehydrogenase
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NAD(P)H dehydrogenase (quinone)
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NAD(P)H menadione reductase
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NAD(P)H quinone reductase
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NAD(P)H-quinone dehydrogenase
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NAD(P)H-quinone oxidoreductase
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NAD(P)H-quinone reductase
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NAD(P)H:(quinone-acceptor) oxidoreductase
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NAD(P)H:menadione oxidoreductase
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NAD(P)H:paraquat diaphorase
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NADH-menadione reductase
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NADH-menaquinone reductase
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NADH:quinone reductase
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NADPH DT-diaphorase
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NADPH:quinone oxidoreductase
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NADPH:quinone reductase
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Naphthoquinone reductase
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p-Benzoquinone reductase
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P36
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Phylloquinone reductase
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Quinone reductase
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Reduced NAD(P)H dehydrogenase
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Viologen accepting pyridine nucleotide oxidoreductase
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Vitamin K reductase
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zeta-Crystallin
zeta-crystallin homolog protein
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zeta-crystallin/NADPH:quinone oxidoreductase
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zeta-Crystallin/quinone reductase
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zeta-Crystallin
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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reduction
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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.
CAS REGISTRY NUMBER
COMMENTARY
9032-20-6
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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
2 1,2-naphthoquinone + NADPH + H+
? + NADP+
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the activity with 9,10-phenanthrenequinone and with 1,2-naphthoquinone is equal
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?
2 9,10-phenanthrenequinone + NADPH + H+
? + NADP+
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70% of the activity with 9,10-phenanthrenequinone
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?
9,10-phenanthrenequinone + NADPH + H+
9,10-phenanthrenequinol + NADP+
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?
menadione + NADPH + H+
menadiol + NADP+
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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
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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enzyme reduces ortho-quinones in the presence of NADPH but is not active with 2-alkenals
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?
NATURAL SUBSTRATE
NATURAL 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
additional information
?
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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
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-
?
additional information
?
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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
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
NADPH, but not NADH, competitively prevents binding of zeta-crystallin to RNA, suggesting that the cofactor-binding site is involved in RNA binding
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dicoumarol
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presence of dicoumarol decreases the production of hydroxyl radical and attenuates DNA strand-breaks in MCF-7 cells treated with menadione
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). QOR_HUMAN
329
0
35207
Swiss-Prot
Mitochondrion (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallographic structure of human zeta-crystallin is reported. Enzyme shows a tetrameric structure
structure in the free state at 2.3 A resolution. VAT-1 forms a dimer with the conserved NADPH-binding cleft on each protomer. The structure of VAT-1 in the NADP-bound state at 2.6 A resolution shows that NADP binds the binding cleft to create a putative active site with the nicotine ring
PROTEIN VARIANTS
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
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rao, P.V.; Zigler, J.S.
Purification and characterization of zeta-crystallin/quinone reductase from guinea pig liver
Biochim. Biophys. Acta
1117
315-320
1992
Cavia porcellus, Homo sapiens
Fernandez, M.R.; Porte, S.; Crosas, E.; Barbera, N.; Farres, J.; Biosca, J.A.; Pares, X.
Human and yeast zeta-crystallins bind AU-rich elements in RNA
Cell. Mol. Life Sci.
64
1419-1427
2007
Saccharomyces cerevisiae, Homo sapiens
Porte, S.; Crosas, E.; Yakovtseva, E.; Biosca, J.A.; Farres, J.; Fernandez, M.R.; Pares, X.
MDR quinone oxidoreductases: the human and yeast zeta-crystallins
Chem. Biol. Interact.
178
288-294
2009
Saccharomyces cerevisiae (P38230), Saccharomyces cerevisiae, Homo sapiens (Q08257), Homo sapiens
Nutter, L.M.; Ngo, E.O.; Fisher, G.R.; Gutierrez, P.L.
DNA strand scission and free radical production in menadione-treated cells. Correlation with cytotoxicity and role of NADPH quinone acceptor oxidoreductase
J. Biol. Chem.
267
2474-2479
1992
Homo sapiens
Porte, S.; Moeini, A.; Reche, I.; Shafqat, N.; Oppermann, U.; Farres, J.; Pares, X.
Kinetic and structural evidence of the alkenal/one reductase specificity of human zeta-crystallin
Cell. Mol. Life Sci.
68
1065-1077
2011
Homo sapiens (Q08257)
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