Information on EC 1.8.1.15 - mycothione reductase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.8.1.15
-
RECOMMENDED NAME
GeneOntology No.
mycothione reductase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 mycothiol + NAD(P)+ = mycothione + NAD(P)H + H+
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
arsenate detoxification III (mycothiol)
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mycothiol oxidation
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SYSTEMATIC NAME
IUBMB Comments
mycothiol:NAD(P)+ oxidoreductase
Contains FAD. No activity with glutathione, trypanothione or coenzyme A as substrate.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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in vivo Mtr knockout strain shows that the enzyme is involved in arsenate (As(V)) resistance suggesting a possible relation with the arsenate reductase activities
metabolism
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cellular mycothiol metabolism, overview. Under stress conditions, proteins are oxidized to mixed disulfides with MSH to form S-mycothiolated proteins that is reversed by the Mrx1/Mtr/MSH pathway
physiological function
additional information
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-dimethylbenzoquinone + NADPH
?
show the reaction diagram
-
-
-
?
2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
show the reaction diagram
-
-
-
-
?
2-methyl-1,4-naphthoquinone + alpha-NADPH
?
show the reaction diagram
-
-
-
?
5,8-dihydroxy-1,4-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
?
5-(benzyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate + NADPH
?
show the reaction diagram
-
a 5,5'-dithiobis-2-nitrobenzoic acid (DTNB)-coupled assay is developed. The mixed disulfide substrate liberates one molecule of TNB on NADPH-dependent reduction by Mycobacterium tubercolosis reductase. The liberated mycothiol analogue then reacts with DTNB to regenerate the mixed disulfide substrate and another molecule of TNB. Reaction progress can be measured by the increase in absorbance (412 nm) from the two molecules of TNB produced per turn of this catalytic cycle
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-
?
5-hydroxy-1,4-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
?
7-methyljuglone + NADPH
?
show the reaction diagram
-
potent subversive substrate
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-
?
8-chloro-5-methoxy-7-methyl-1,4-naphthoquinone + NADPH
?
show the reaction diagram
-
-
-
-
?
AcCys-GlcN + NADPH
?
show the reaction diagram
-
-
-
-
?
AcCys-GlcN-1-O-CH2Ph + NADPH
?
show the reaction diagram
-
-
-
-
?
AcCys-GlcN-1-O-CH3 + NADPH
?
show the reaction diagram
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-
-
-
?
benzyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
show the reaction diagram
-
-
-
-
?
benzyl 2-(N-acetyl-L-cysteinyl)amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
show the reaction diagram
-
-
-
-
?
des-myo-inositol mycothione + NADH
?
show the reaction diagram
des-myo-inositol mycothione + reduced beta-nicotinamide hypoxanthine dinucleotide
?
show the reaction diagram
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-
?
des-myo-inositol mycothione + reduced beta-nicotinamide hypoxanthine dinucleotide phosphate
?
show the reaction diagram
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-
?
des-myo-inositol mycothione + thio-NADH
?
show the reaction diagram
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-
?
des-myo-inositol mycothione + thio-NADPH
?
show the reaction diagram
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-
?
desmyoinositol mycothione + NADPH
?
show the reaction diagram
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?
dimeric mycothiol disulfide + NADPH
2 mycothione + H+
show the reaction diagram
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-
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-
?
diospyrin + NADPH
?
show the reaction diagram
-
subversive substrate
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-
?
DTNB + NADPH
?
show the reaction diagram
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-
-
?
juglone + NADPH
?
show the reaction diagram
-
subversive substrate
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-
?
menadione + NADPH
?
show the reaction diagram
-
subversive substrate
-
-
?
methyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
show the reaction diagram
-
-
-
-
?
mycothione + NADPH
mycothiol + NADP+
show the reaction diagram
mycothione + NADPH + H+
2 mycothiol + NADP+
show the reaction diagram
mycothione + NADPH + H+
mycothiol + NADP+
show the reaction diagram
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-
-
-
?
neodiospyrin + NADPH
?
show the reaction diagram
-
subversive substrate
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-
?
additional information
?
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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
mycothione + NADPH
mycothiol + NADP+
show the reaction diagram
mycothione + NADPH + H+
2 mycothiol + NADP+
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NADPH
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-(5-bromo-2-methoxyphenyl)acrylonitrile
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time-dependent inhibitor
DMSO
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in the presence of 4% (v/v) DMSO, Mycobacterium tubercolosis reductase activity is reduced by only 10%. It is recommended that the DMSO content in sets of inhibition assays should be kept at a constant with 4% (v/v) DMSO as the upper limit
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4
2,6-dimethylbenzoquinone
-
-
0.463
2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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30C, pH 7.5
0.24
2-methyl-1,4-naphthoquinone
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-
0.34
5,8-Dihydroxy-1,4-naphthoquinone
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-
0.268
5-(benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate
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-
0.54
5-hydroxy-1,4-naphthoquinone
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2.365
7-methyljuglone
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pH 7.6, 30C
0.142
8-chloro-5-methoxy-7-methyl-1,4-naphthoquinone
-
pH 7.6, 30C
0.055
alpha-NADPH
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des-myo-inositol mycothione as second substrate
0.438
benzyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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30C, pH 7.5
0.438
benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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0.008
beta-NADPH
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des-myo-inositol mycothione as second substrate
0.4 - 0.51
des-myo-inositol mycothione
0.118
diospyrin
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pH 7.6, 30C
1.088
juglone
-
pH 7.6, 30C
0.732
menadione
-
pH 7.6, 30C
0.61
methyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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30C, pH 7.5
0.073 - 0.113
mycothione
0.043
NADH
-
des-myo-inositol mycothione as second substrate
0.308
neodiospyrin
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pH 7.6, 30C
0.2
reduced beta-nicotinamide hypoxanthine dinucleotide
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des-myo-inositol mycothione as second substrate
0.023
reduced beta-nicotinamide hypoxanthine dinucleotide phosphate
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des-myo-inositol mycothione as second substrate
0.09
thio-NADH
-
des-myo-inositol mycothione as second substrate
0.001
thio-NADPH
-
des-myo-inositol mycothione as second substrate
additional information
additional information
-
stopped-flow kinetics
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
70.05
2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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30C, pH 7.5
115
5-(benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate
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0.254
7-methyljuglone
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pH 7.6, 30C
0.435
8-chloro-5-methoxy-7-methyl-1,4-naphthoquinone
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pH 7.6, 30C
36.99
benzyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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30C, pH 7.5
37
benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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-
0.033
diospyrin
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pH 7.6, 30C
0.324
juglone
-
pH 7.6, 30C
0.483
menadione
-
pH 7.6, 30C
25.54
methyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
-
30C, pH 7.5
68.76 - 69
mycothione
20 - 30
NADH
129
NADPH
0.063
neodiospyrin
-
pH 7.6, 30C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.427
5-(benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate
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-
0.09
benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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-
0.61
mycothione
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-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.11
2-(5-bromo-2-methoxyphenyl)acrylonitrile
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kinact: 0.22/min
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
gene is actively transcribed during logarithmic growth
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
50000
-
alpha2, 2 * 50000, SDS-PAGE
92000
-
recombinant enzyme, gel filtration
100000
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gel filtration
137000
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recombinant enzyme, dynamic light scattering analysis
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
alpha2, 2 * 50000, SDS-PAGE
additional information
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant tagged enzyme by affinity chromatography and gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli as a His-tagged fusion protein
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expression in Mycobacterium smegmatis pyrF
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functional recombinant expression of tagged enzyme
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overexpression of His6-tagged enzyme from expression vector pXMJ19 in Corynebacterium glutamicum. Transfected cells show increased tolerance to reactive oxygen species induced by oxidants, bactericidal antibiotics, alkylating agents, and heavy metals
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is positively regulated by SigH, the stress-responsive extracytoplasmic function-sigma (ECF-sigma) factor
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
overexpression of mycothiol disulfide reductase enhances Corynebacterium glutamicum robustness by modulating cellular redox homeostasis and antioxidant proteins under oxidative stress. Overexpression of Mtr causes a marked increase in the ratio of reduced to oxidized mycothiol (MSH:MSSM), and significantly enhances the activities of a variety of antioxidant enzymes, including mycothiol peroxidase (MPx), mycoredoxin 1 (Mrx1), thioredoxin 1 (Trx1), and methionine sulfoxide reductase A (MsrA). The mycothione levels of enzyme expressing cells are lower than those of untransfectde cells under H2O2, ciprofloxacin, CdCl2, N-ethylmaleimide, iodoacetamide, methylglyoxal, and 1-chloro-2,4-dinitrobenzene stresses, no significant difference in MSH or MSSM levels when both cells are exposed to formaldehyde and rifamycin SV
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
medicine
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the enzyme is sensitive to free radical generating antituberculosis drugs and may be useful target for new drug development
molecular biology
-
a DTNB-coupled assay is developed for time-dependent inhibition of Mycobacterium tubercolosis reductase employing a benzyl glycoside analogue of MSH, from which an efficient mixed disulfide substrate is chemically recycled in situ, thereby greatly reducing the substrate quantities needed for such assays
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