Information on EC 1.8.1.8 - protein-disulfide reductase

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

EC NUMBER
COMMENTARY hide
1.8.1.8
-
RECOMMENDED NAME
GeneOntology No.
protein-disulfide reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
protein-dithiol + NAD(P)+ = protein-disulfide + NAD(P)H + H+
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
redox reaction
-
-
-
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reduction
SYSTEMATIC NAME
IUBMB Comments
protein-dithiol:NAD(P)+ oxidoreductase
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CAS REGISTRY NUMBER
COMMENTARY hide
9029-19-0
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
protein disulfide reductase ERdj5 mediates endoplasmic reticulum-associated degradation in concert with EDEM1
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2,6-dimethyl-1,4-benzoquinone + NAD(P)H
2,6-dimethyl-1,4-benzoquinol + NAD(P)+
show the reaction diagram
-
-
-
-
?
5-hydroxy-1,4-naphthoquinone + NAD(P)H
5-hydroxy-1,4-naphthoquinol + NAD(P)+
show the reaction diagram
-
-
-
-
?
barley alpha-amylase/subtilisin inhibitor + ?
?
show the reaction diagram
-
-
-
-
?
DTNB + NAD(P)H
5-mercapto-2-nitrobenzoate + NAD(P)+
show the reaction diagram
-
-
-
-
-
insulin disulfide + ?
?
show the reaction diagram
insulin disulfide + NAD(P)H
? + NAD(P)+
show the reaction diagram
-
-
-
-
?
insulin disulfide + NADPH
?
show the reaction diagram
NAD(P)H + protein disulfide
NAD(P)+ + protein dithiol
show the reaction diagram
NAD+ + NADH
NADH + NAD+
show the reaction diagram
-
enzyme-catalyzed interconversion
-
-
?
NADH + CoA-SS-CoA + H+
NAD+ + CoA
show the reaction diagram
-
-
-
-
?
NADH + CoA-SS-pantetheine-4'-phosphate
NAD+ + CoA + 4'-phosphopantetheine
show the reaction diagram
-
-
-
-
?
NADH + pantethine 4',4''-diphosphate
NAD+ + 4'-phosphopantetheine
show the reaction diagram
-
-
-
-
?
NADH + pantethine 4',4''-diphosphate + H+
NAD+ + 4'-phosphopantetheine
show the reaction diagram
-
-
-
-
?
peroxiredoxin disulfide + NAD(P)H
reduced peroxiredoxin + NAD(P)+
show the reaction diagram
-
-
-
-
ir
peroxiredoxin disulfide + NADH
reduced peroxiredoxin + NAD+
show the reaction diagram
-
enzyme recycles peroxiredoxin AhpC, enzyme acts in a catalytic cycle reaction together with peroxidase forming the bacterial alkyl hydroperoxide reductase system, formerly known as F-52a
-
-
ir
protein disulfide + NAD(P)H
protein dithiol + NAD(P)+
show the reaction diagram
protein disulfide + NADH
protein dithiol + NAD+
show the reaction diagram
thio-NAD+ + NAD(P)H
NAD+ + thio-NAD(P)H
show the reaction diagram
-
-
-
-
?
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
peroxiredoxin disulfide + NADH
reduced peroxiredoxin + NAD+
show the reaction diagram
-
enzyme recycles peroxiredoxin AhpC, enzyme acts in a catalytic cycle reaction together with peroxidase forming the bacterial alkyl hydroperoxide reductase system, formerly known as F-52a
-
-
ir
protein disulfide + NAD(P)H
protein dithiol + NAD(P)+
show the reaction diagram
-
-
-
-
r
protein disulfide + NADH
protein dithiol + NAD+
show the reaction diagram
-
the activity of MdrA and the organization of mdrA in a transcriptional unit with oxidative stress genes are consistent with a role in the oxidative stress response of Methanosarcina acetivorans
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-
?
additional information
?
-
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the disulfide reductase system varies with the organism, overview
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-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)H
-
NADH/SS binding domain structure, residues 328-449, physiological reductant is NADH, NADH is strongly favoured over NADPH
NADP+
-
tightly but noncovalentyl bound, 1 molecule per subunit, physiological cofactor
NADPH
thioredoxin
the enzyme contains six thioredoxin domains
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron-sulfur cluster
-
the enzyme contains an intermolecular Fe-S cluster that controls oligomerization as a mechanism to regulate protein disulfide reductase activity
Zn2+
-
in the crystal unit cell two neighboring PfPDO molecules are associated by two zinc ions to form a dimer in the crystal
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2'-phospho-ADP-ribose
-
inhibition of 2,6-dimethyl-1,4-benzoquinone reduction
AgNO3
-
0.009 mM, 66% inhibition
arsenite
CdSO4
-
0.005 mM, 91% inhibition
CuSO4
-
0.015 mM, complete inhibition
HgCl2
-
0.002 mM, 92% inhibition
idoacetate
-
0.054 mM, 57% inhibition
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N-ethylmaleimide
-
-
NADP+
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inhibition of 2,6-dimethyl-1,4-benzoquinone reduction
p-chloromercuribenzoate
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0.054 mM, 88% inhibition
ZnSO4
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0.003 mM, 82% inhibition
additional information
-
enzyme is inhibited by alkylation of either pair of Cys residues, i.e. Cys129-Cys132, or Cys345-Cys348
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0016 - 0.011
2,6-dimethyl-1,4-benzoquinone
0.00039 - 0.0055
5-hydroxy-1,4-naphthoquinone
7.4
CoA-SS-CoA
-
-
0.028 - 0.036
NADH
0.00044 - 0.002
NADPH
0.65
pantethine 4',4''-diphosphate
-
-
0.0054 - 0.018
thio-NAD+
additional information
additional information
-
steady-state kinetics, ping-pong kinetic mechanism with NAD(P)H and 2,6-dimethyl-1,4-benzoquinone or 5-hydroxy-1,4-naphthoquinone
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0077 - 2.8
2,6-dimethyl-1,4-benzoquinone
0.0079 - 2.5
5-hydroxy-1,4-naphthoquinone
0.0087
NAD(P)H
Mycobacterium tuberculosis
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pH 7.5, 25C, with thio-NAD+
2.5 - 3.6
NADH
0.0077 - 0.0079
NADPH
0.0087 - 3.6
thio-NAD+
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0008
2'-phospho-ADP-ribose
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-
0.000006
NADP+
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-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.8
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substrate: pantethine 4',4''-diphosphate
6.9 - 7.4
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.2 - 7.8
-
pH 6.2: about 50% of activity maximum, pH 7.8: about 20% of activity maximum
additional information
-
seven times as active in phosphate buffer as in Tris at the same pH
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.9
-
isoelectric focusing
9.23
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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the enzyme is at a low level in log-phase cells but increases up to 10fold early in the stationary phase and has a similar specific activity in both the mother cell and the forespore compartment. The enzyme activity falls only slowly during spore germination and outgrowth
Manually annotated by BRENDA team
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highest level in cells late in sporulation and in dormant spores
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
ERp16 mediates disulfide bond formation in the endoplasmic reticulum and plays an important role in cellular defense against prolonged ER stress
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
UNIPROT
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Neisseria meningitidis serogroup A / serotype 4A (strain Z2491)
Neisseria meningitidis serogroup B (strain MC58)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25000
-
SDS-PAGE
29000
-
gel filtration
34900
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gel filtration
122000
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gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
additional information
-
the redox-active disulfide in the N-terminal domain, Cys129-Cys132, of the enzyme is in functional communication with the thioredoxin reductase-like disulfide center in the C-terminal portion, Cys345-Cys348, and with FAD
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapour diffusion method
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sitting drop vapor diffusion method, using 10% (w/v) PEG 8000, 100 mM HEPES (pH 7.5), and 8 mM cystin at 20C
purified recombinant His-tagged enzyme LpdA, hanging drop vapour diffusion method at room temperature, 0.003 ml protein solution containing 25 mg/ml protein, 10 mM HEPES, pH 7.5, mixed with 0.002 ml precipitant solution containing 0.1 M trisodium citrate, pH 5.4-5.8, 2.5-5.0% PEG 6000, 3-7 days depending on the pH, crystallization takes longer at higher pH-value, crystals are immersed in 10% PEG 6000, 100 mM MES, pH 5.75, and 25% glycerol, X-ray diffraction structure determination and analysis at 2.8 A resolution
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sitting-drop vapor diffusion method, crystals belong to the hexagonal space group P6522 with cell dimensions of a = b = 110.3 and c = 68.5 and with one molecule in the asymmtric unit. The structure is solved by multiple isomorphous replacement including anomalous scattering data. The structure is refined to 1.9 resolution
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analysis of the X-ray structure at 2.0 A resolution
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5
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5C or 22C, irreversible inactivation
437710
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60
-
10 min, stable
70
-
10 min, complete inactivation
90
-
3 h, no loss of activity
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, 8 weeks, stable
-20C, stable fo at least 3 months without any loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
HisTrap column chromatography and HiLoad Superdex 16/60 75 gel filtration
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Ni2+-NTA affinity chromatography
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recombinant enzyme
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recombinant His-tagged enzyme from Escherichia coli
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Superdex 200 gel filtration
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
expressed in Escherichia coli and in HEK-293 cells
expression in Escherichia coli
expression in Escherichia coli. Expression of ERp16 in HeLa cells inhibits the induction of apoptosis by agents that elicit ER stress, including brefeldin A, tunicamycin, and dithiothreitol
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gene lpdA, expression in Escherichia coli strain BL21(DE3) as His-tagged protein
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overexpression in Escherichia coli
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
enzyme is inhibited by mutation of either pair of Cys residues, i.e. Cys129-Cys132, or Cys345-Cys348, construction and functional analysis of a chimeric mutant enzyme comprising the enzymes N-terminal domain attached to the N-terminus of thioredoxin reductase from Escherichia coli, the chimeric mutant can reduce thioredoxin, which the wild-type AhpF is not capable of, overview
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