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Information on EC 1.8.1.15 - mycothione reductase
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1.8.1.15 mycothione reductaseIUBMB Comments
Contains FAD. No activity with glutathione, trypanothione or coenzyme A as substrate.
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Word Map
- 1.8.1.15
- tuberculosis
- mycoredoxins
-
corynebacterium
- glutamicum
- actinobacteria
-
dithiolic
-
antimycobacterial
-
oxidized-reduced
-
peroxidatic
-
low-molecular
-
nadph-binding
- isoniazid
-
antituberculosis
-
monothiolic
-
ms-based
-
mycothiol-dependent
-
small-angle
- peroxidases
- natalensis
-
sulfenic
- analysis
- molecular biology
- medicine
The enzyme appears in viruses and cellular organisms
Synonyms
mycothiol disulfide reductase, mtmtr, mycothiol disulphide reductase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
MtMtr
MTR
mycothiol disulfide reductase
mycothiol disulphide reductase
mycothiol-disulfide reductase
-
-
-
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mycothione reductase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 mycothiol + NAD(P)+ = mycothione + NAD(P)H + H+
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-
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
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redox reaction
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-
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reduction
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-
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-
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
mycothiol:NAD(P)+ oxidoreductase
Contains FAD. No activity with glutathione, trypanothione or coenzyme A as substrate.
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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-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
-
-
-
-
?
5-(benzyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate + NADPH
?
-
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
-
-
?
8-chloro-5-methoxy-7-methyl-1,4-naphthoquinone + NADPH
?
-
-
-
-
?
benzyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
-
-
-
-
?
benzyl 2-(N-acetyl-L-cysteinyl)amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
-
-
-
-
?
des-myo-inositol mycothione + reduced beta-nicotinamide hypoxanthine dinucleotide
?
-
-
-
?
des-myo-inositol mycothione + reduced beta-nicotinamide hypoxanthine dinucleotide phosphate
?
-
-
-
?
methyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide + NADPH
?
-
-
-
-
?
mycothione + NADPH
mycothiol + NADP+
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the enzyme is involved in mycothiol metabolism. Mycothiol may play an important role in the survival and adaption of mycobacteria to oxidative stress caused by normal metabolism, ir induced by the action of anti-tubercular drugs
-
-
?
additional information
?
-
-
many naphthoquinones operate as subversive substrates. The native functions of these enzyme involves the NADPH-dependent reduction of disulfide bonds in the substrate. The enzyme-mediated toxicity of quinones/naphthoquinones is a consequence of their enzymatic reduction to semiquinone radicals. The naphthoquinone is then regenerated via the concomitant reduction of oxygen to toxic superoxide anion radicals. In this manner the naphthoquinone substrate is regenerated and the futile redox cycle continues
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-
additional information
?
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mycothiol disulfide reductase (Mtr) interacts with the oxido-reductase Mycoredoxin-1 (Mrx-1). the MtMtr-MtMrx-1 interaction is characterized by a fast exchange regime, critical residues by NMR spectroscopy and docking studies, overview
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-
-
additional information
?
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mycothiol disulfide reductase (Mtr) interacts with the oxido-reductase Mycoredoxin-1 (Mrx-1). the MtMtr-MtMrx-1 interaction is characterized by a fast exchange regime, critical residues by NMR spectroscopy and docking studies, overview
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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
mycothione + NADPH
mycothiol + NADP+
-
the enzyme is involved in mycothiol metabolism. Mycothiol may play an important role in the survival and adaption of mycobacteria to oxidative stress caused by normal metabolism, ir induced by the action of anti-tubercular drugs
-
-
?
additional information
?
-
-
mycothiol disulfide reductase (Mtr) interacts with the oxido-reductase Mycoredoxin-1 (Mrx-1). the MtMtr-MtMrx-1 interaction is characterized by a fast exchange regime, critical residues by NMR spectroscopy and docking studies, overview
-
-
-
additional information
?
-
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mycothiol disulfide reductase (Mtr) interacts with the oxido-reductase Mycoredoxin-1 (Mrx-1). the MtMtr-MtMrx-1 interaction is characterized by a fast exchange regime, critical residues by NMR spectroscopy and docking studies, overview
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
the FAD-binding- and interface domain participate in the dimer formation
NADPH
-
structure analysis of the two NADPH-binding domains inside the dimeric MtMtr in different conformations
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.463
2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
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30°C, pH 7.5
0.268
5-(benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate
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-
0.142
8-chloro-5-methoxy-7-methyl-1,4-naphthoquinone
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pH 7.6, 30°C
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
-
30°C, 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
0.61
methyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
-
30°C, pH 7.5
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
0.001
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
LITERATURE
IMAGE
70.05
2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
-
30°C, pH 7.5
115
5-(benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate
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-
0.435
8-chloro-5-methoxy-7-methyl-1,4-naphthoquinone
-
pH 7.6, 30°C
36.99
benzyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
-
30°C, pH 7.5
37
benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
-
-
25.54
methyl 2-(-N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
-
30°C, pH 7.5
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.427
5-(benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside)-dithio-2-nitrobenzoate
-
-
0.09
benzyl 2-(N-acetyl-L-cysteinyl) amino-2-deoxy-alpha-D-glucopyranoside disulfide
-
-
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
gene is actively transcribed during logarithmic growth
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
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
-
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
physiological function
-
in a mycothione disulfide reductase mutant, mycothiol levels decrease only upon treatment with peroxide
physiological function
-
in Mycobacterium tuberculosis, the enzyme is part of a versatile machinery of the mycothiol-dependent system, containing the proteins mycothiol disulfide reductase (Mtr), the oxido-reductase mycoredoxin-1 (Mrx-1) and the alkyl-hydroperoxide subunit E (AhpE), system overview. The mycothiol-dependent protein ensemble regulates the balance of oxidized-reduced mycothiol, to ensure a reductive intracellular environment for optimal functioning of its proteins even uponexposure to oxidative stress
physiological function
-
the enzyme maintains intracellular redox homeostasis. The physiological roles of Mtr in resistance to oxidative stresses are corroborated by decreased reactive oxygen species levels, reduced carbonylation damage, decreased loss of reduced protein thiols, and a massive increase in the levels of reversible protein thiols in Mtr-overexpressing cells exposed to stressful conditions
physiological function
-
in Mycobacterium tuberculosis, the enzyme is part of a versatile machinery of the mycothiol-dependent system, containing the proteins mycothiol disulfide reductase (Mtr), the oxido-reductase mycoredoxin-1 (Mrx-1) and the alkyl-hydroperoxide subunit E (AhpE), system overview. The mycothiol-dependent protein ensemble regulates the balance of oxidized-reduced mycothiol, to ensure a reductive intracellular environment for optimal functioning of its proteins even uponexposure to oxidative stress
-
physiological function
Mycolicibacterium smegmatis mc(2)155 / ATCC 700084
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in a mycothione disulfide reductase mutant, mycothiol levels decrease only upon treatment with peroxide
-
additional information
-
MtMtr is predicted to undergo a mono-to-dimeric equilibrium in solution during catalysis. Enzyme homology structure modelling
additional information
-
MtMtr is predicted to undergo a mono-to-dimeric equilibrium in solution during catalysis. Enzyme homology structure modelling
-
Show AA Sequence and Transmembrane Helices (205 entries)
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Please use the AA Sequence and Transmembrane Helices Search for a specific query.
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
dimer
-
2 * 49800, about, sequence calculation, spectroscopic and dynamic light scattering structure analysis, modelling
dimer
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2 * 49800, about, sequence calculation, spectroscopic and dynamic light scattering structure analysis, modelling
-
additional information
-
MtMtr is predicted to undergo a mono-to-dimeric equilibrium in solution during catalysis. Enzyme homology structure modelling, the FAD-binding- and interface domain participate in the dimer formation
additional information
-
MtMtr is predicted to undergo a mono-to-dimeric equilibrium in solution during catalysis. Enzyme homology structure modelling, the FAD-binding- and interface domain participate in the dimer formation
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
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
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PURIFICATION/commentary
ORGANISM
UNIPROT
LITERATURE
recombinant tagged enzyme by affinity chromatography and gel filtration
-
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CLONED/commentary
ORGANISM
UNIPROT
LITERATURE
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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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
medicine
-
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
analysis
-
rapid method for the relative quantification of mycothiol using high-sensitivity mass spectrometry with selected ion monitoring. The method uses only minimal sample cleanup, and does not require advanced chromatographic equipment or fluorescent compounds
analysis
Mycolicibacterium smegmatis mc(2)155 / ATCC 700084
-
rapid method for the relative quantification of mycothiol using high-sensitivity mass spectrometry with selected ion monitoring. The method uses only minimal sample cleanup, and does not require advanced chromatographic equipment or fluorescent compounds
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Patel, M.P.; Blanchard, J.S.
Synthesis of des-myo-inositol mycothiol and demonstration of a mycobacterial specific reductase activity
J. Am. Chem. Soc.
120
11538-11539
1998
Mycobacterium tuberculosis
-
brenda
Patel, M.P.; Blanchard, J.S.
Expression, purification, and characterization of Mycobacterium tuberculosis mycothione reductase
Biochemistry
38
11827-11833
1999
Mycobacterium tuberculosis, Mycobacterium tuberculosis (P9WHH3), Mycobacterium tuberculosis H37Rv (P9WHH3)
brenda
Patel, M.P.; Blanchard, J.S.
Mycobacterium tuberkulosis mycothione reductase: pH dependence of the kinetic parameters and kinetic isotope effects
Biochemistry
40
5119-5126
2001
Mycobacterium tuberculosis
brenda
Hayward, D.; Wiid, I.; van Helden, P.
Differential expression of mycothiol pathway genes: are they affected by antituberculosis drugs?
IUBMB Life
56
131-138
2004
Mycobacterium tuberculosis variant bovis
brenda
Mahapatra, A.; Mativandlela, S.P.; Binneman, B.; Fourie, P.B.; Hamilton, C.J.; Meyer, J.J.; van der Kooy, F.; Houghton, P.; Lall, N.
Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase
Bioorg. Med. Chem.
15
7638-7646
2007
Mycobacterium tuberculosis
brenda
Newton, G.L.; Buchmeier, N.; Fahey, R.C.
Biosynthesis and functions of mycothiol, the unique protective thiol of actinobacteria
Microbiol. Mol. Biol. Rev.
72
471-494
2008
Mycobacterium tuberculosis
brenda
Stewart, M.J.; Jothivasan, V.K.; Rowan, A.S.; Wagg, J.; Hamilton, C.J.
Mycothiol disulfide reductase: solid phase synthesis and evaluation of alternative substrate analogues
Org. Biomol. Chem.
6
385-390
2008
Mycobacterium tuberculosis
brenda
Ordonez, E.; Van Belle, K.; Roos, G.; De Galan, S.; Letek, M.; Gil, J.A.; Wyns, L.; Mateos, L.M.; Messens, J.
Arsenate reductase, mycothiol, and mycoredoxin concert thiol/disulfide exchange
J. Biol. Chem.
284
15107-15116
2009
Corynebacterium glutamicum
brenda
Hamilton, C.J.; Finlay, R.M.; Stewart, M.J.; Bonner, A.
Mycothiol disulfide reductase: A continuous assay for slow time-dependent inhibitors
Anal. Biochem.
388
91-96
2009
Mycobacterium tuberculosis
brenda
Holsclaw, C.M.; Muse, W.B.; Carroll, K.S.; Leary, J.A.
Mass Spectrometric Analysis of Mycothiol levels in wild-type and mycothiol disulfide reductase mutant Mycobacterium smegmatis
Int. J. Mass Spectrom.
305
151-156
2011
Mycolicibacterium smegmatis, Mycolicibacterium smegmatis mc(2)155 / ATCC 700084
brenda
Kumar, A.; Nartey, W.; Shin, J.; Manimekalai, M.S.S.; Grueber, G.
Structural and mechanistic insights into mycothiol disulphide reductase and the mycoredoxin-1-alkylhydroperoxide reductase E assembly of Mycobacterium tuberculosis
Biochim. Biophys. Acta
1861
2354-2366
2017
Mycobacterium tuberculosis, Mycobacterium tuberculosis (P9WHH3), Mycobacterium tuberculosis H37Rv (P9WHH3)
brenda
Si, M.; Zhao, C.; Zhang, B.; Wei, D.; Chen, K.; Yang, X.; Xiao, H.; Shen, X.
Overexpression of mycothiol disulfide reductase enhances Corynebacterium glutamicum robustness by modulating cellular redox homeostasis and antioxidant proteins under oxidative stress
Sci. Rep.
6
29491
2016
Corynebacterium glutamicum
brenda
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