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Information on EC 1.8.1.B1 - thioredoxin glutathione reductase and Organism(s) Schistosoma mansoni and UniProt Accession Q962Y6
for references in articles please use BRENDA:EC1.8.1.B1preliminary BRENDA-supplied EC number
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1.8.1.B1 thioredoxin glutathione reductaseSpecify your search results
Word Map
- 1.8.1.B1
- schistosoma
- schistosomiasis
- worm
- mansoni
- praziquantel
- glutaredoxin
- selenocysteine
-
antischistosomal
- gssg
- auranofin
-
platyhelminth
- flatworm
- dtnb
- fluke
-
sjtgr
- fasciola
-
oxadiazole
- cysticerci
-
hysteretic
- medicine
-
taenia
-
trematode
-
echinococcus
- granulosus
-
schistosomicidal
- crassiceps
- gigantica
-
selenocysteine-containing
- furoxans
- analysis
The taxonomic range for the selected organisms is: Schistosoma mansoni
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
thioredoxin glutathione reductase, smtgr, thioredoxin-glutathione reductase, tgrsec, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
TGR
TGR
thioredoxin glutathione reductase
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
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
additional information
?
-
-
the parasite-specific enzyme thioredoxin glutathione reductase is a component of the defense system
-
-
?
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
-
-
-
-
?
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
-
the enzyme of the parasite essential for the survival of schistosomes in the mammalian host
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
the enzyme of the parasite essential for the survival of schistosomes in the mammalian host
-
-
?
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
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
-
the enzyme of the parasite essential for the survival of schistosomes in the mammalian host
-
-
?
additional information
?
-
-
the parasite-specific enzyme thioredoxin glutathione reductase is a component of the defense system
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
the enzyme of the parasite essential for the survival of schistosomes in the mammalian host
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
selenium
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,8-naphthyridine-2 carboxylate
mixed inhibition. 1,8-Naphthyridine-2 carboxylate prevents Tyr296 from rotating, a process necessary for NADPH binding and enzyme reduction. It inhibits by stabilizing a protein conformation whose affinity for NADPH is greatly reduced
-
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(1,3-dimethyl-1H-pyrazol-4-yl)methanone]
-
-
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(4-methoxyphenyl)methanone]
-
-
1,3,4-oxadiazole-2-sulfone
-
shows potent schistomicidal activity (LD50 above 0.01 mM) against Schistosoma mansoni, Schistosoma japonicum and Schistosoma hematobium, particularly against immature flukes. The compounds exceeds the standard set by WHO for antischistosome lead compounds. Kills schistosomes within 1 h of administration
-
2-((4-chlorophenyl)sulfonal)-6-methoxy-3-nitropyridine
-
shows potent schistomicidal activity (LD50 above 0.01 mM) against Schistosoma mansoni, Schistosoma japonicum and Schistosoma hematobium, particularly against immature flukes. Kills schistosomes within 1 h of administration
-
2-(4-chlorophenoxy)-6-methyl-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
-
-
2-(4-ethoxyphenoxy)-6-methyl-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
-
-
4-aminopiazthiole
inhibit the enzyme in a NADPH-dependent manner, and the inhibition appears to be irreversible even upon extensive dilution of the inhibited protein
-
5-bromo-N-ethyl-3,4-dinitrothiophen-2-amine
-
at 0.005 microM, 100 % larval death at 48 hours
5-chloro-N-[4-[ethyl(phenyl)sulfamoyl]phenyl]-2-(methanesulfonyl)pyrimidine-4-carboxamide
-
-
-
6-methyl-2-phenoxy-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
-
-
6-nitrobenzo[b]thiophene-1,1-dioxide
-
shows potent schistomicidal activity (LD50 above 0.01 mM) against Schistosoma mansoni, Schistosoma japonicum and Schistosoma hematobium, particularly against immature flukes. The compounds exceeds the standard set by WHO for antischistosome lead compounds. Kills schistosomes within 1 h of administration
-
7-[(4-methoxyphenyl)[(4-methylpyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
-
-
-
diethyl 2-(3-bromo-6-oxo-6H-anthra[1,9-cd][1,2]oxazol-4-yl)-3-oxobutanedioate
-
-
-
indole-3-carbinol
inhibit the enzyme in a NADPH-dependent manner, and the inhibition appears to be irreversible even upon extensive dilution of the inhibited protein
methyl (5-[1-[(tert-butoxycarbonyl)amino]-2-phenylethyl]-1,3,4-oxadiazole-2-sulfonyl)acetate
-
-
-
P-1,3-benzothiazol-2-yl-N-(2-fluorophenyl)-P-phenylphosphinic amide
-
-
P-1,3-benzothiazol-2-yl-N-(5-chloropyridin-2-yl)-P-phenylphosphinic amide
-
-
P-1,3-benzothiazol-2-yl-P-phenyl-N-1,3-thiazol-2-ylphosphinic amide
-
-
pyrazine-3-one
-
shows potent schistomicidal activity (LD50 above 0.01 mM) against Schistosoma mansoni, Schistosoma japonicum and Schistosoma hematobium, particularly against immature flukes. The compounds exceeds the standard set by WHO for antischistosome lead compounds. Kills schistosomes within 1 h of administration
-
auranofin
very potent inhibitor, nearly compete inhibition at 0.01 mM
4-chloro-5-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-2-phenylpyridazin-3(2H)-one
-
-
4-chloro-5-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-2-phenylpyridazin-3(2H)-one
-
at 0.010 microM, 100 % larval death at 48 hours
6-nitro-1H-1-benzothiophene-1,1-dione
-
at 0.010 microM, 100 % larval death at 48 hours
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0612
glutathione disulfide
-
pH not specified in the publication, temperature not specified in the publication
0.00434
5,5'-dithiobis(2-nitrobenzoic acid)
-
pH not specified in the publication, temperature not specified in the publication
0.043
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.107
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.169
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.187
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.23
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.23
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.319
5,5'-dithiobis(2-nitrobenzoic acid)
-
wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.375
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.406
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C28A/C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.013
GSSG
-
mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.016
GSSG
-
mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.023
GSSG
-
mutant enzyme C28A/C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.024
GSSG
-
mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.031
GSSG
-
mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.036
GSSG
-
mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.042
GSSG
-
wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.071
GSSG
-
mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.189
GSSG
-
mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.007
thioredoxin disulfide
-
mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.007
thioredoxin disulfide
-
mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.008
thioredoxin disulfide
-
mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.008
thioredoxin disulfide
-
mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.008
thioredoxin disulfide
-
wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.015
thioredoxin disulfide
-
mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.015
thioredoxin disulfide
-
mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.019
thioredoxin disulfide
-
mutant enzyme C28A/C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.022
thioredoxin disulfide
-
mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
5
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
6
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
6
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
6
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
6
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
8
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C28A/C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
16
5,5'-dithiobis(2-nitrobenzoic acid)
-
mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
16
5,5'-dithiobis(2-nitrobenzoic acid)
-
wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.6
GSSG
-
mutant enzyme C28A/C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.7
GSSG
-
mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
3.5
GSSG
-
mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
4
GSSG
-
mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
5
GSSG
-
mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
5
GSSG
-
mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
7
GSSG
-
mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
19.4
GSSG
-
wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
25
GSSG
-
mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
3.5
thioredoxin disulfide
-
mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
8
thioredoxin disulfide
-
mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
8
thioredoxin disulfide
-
mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
9
thioredoxin disulfide
-
mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00129 - 0.00408
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(1,3-dimethyl-1H-pyrazol-4-yl)methanone]
0.00005
2-(4-chlorobenzene-1-sulfonyl)-6-methoxy-3-nitropyridine
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
-
0.00055
2-(4-chlorophenoxy)-6-methyl-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
Schistosoma mansoni
-
-
0.0006
2-(4-ethoxyphenoxy)-6-methyl-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
Schistosoma mansoni
-
-
0.00249 - 0.0063
4-chloro-5-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-2-phenylpyridazin-3(2H)-one
0.00023
5-chloro-N-[4-[ethyl(phenyl)sulfamoyl]phenyl]-2-(methanesulfonyl)pyrimidine-4-carboxamide
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
-
0.00013
5-[[3-(trifluoromethyl)anilino]methyl]quinolin-8-ol
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
-
0.004
6-methyl-2-phenoxy-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
Schistosoma mansoni
-
-
0.00033
7-[(4-methoxyphenyl)[(4-methylpyridin-2-yl)amino]methyl]-2-methylquinolin-8-ol
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
-
0.009
diethyl (3-bromo-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)propanedioate
Schistosoma mansoni
-
-
0.00015
diethyl 2-(3-bromo-6-oxo-6H-anthra[1,9-cd][1,2]oxazol-4-yl)-3-oxobutanedioate
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
-
0.00008
dimethyl (3-bromo-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)propanedioate
Schistosoma mansoni
-
-
0.00039
methyl (5-[1-[(tert-butoxycarbonyl)amino]-2-phenylethyl]-1,3,4-oxadiazole-2-sulfonyl)acetate
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
-
0.000789 - 0.00154
P-1,3-benzothiazol-2-yl-N-(5-chloropyridin-2-yl)-P-phenylphosphinic amide
0.000038
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis(2-furylmethanone)
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.000082
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis(2-furylmethanone)
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.000042
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis(2-thienylmethanone)
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.00051
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis(2-thienylmethanone)
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.00129
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(1,3-dimethyl-1H-pyrazol-4-yl)methanone]
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.002
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(1,3-dimethyl-1H-pyrazol-4-yl)methanone]
Schistosoma mansoni
-
-
0.00408
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(1,3-dimethyl-1H-pyrazol-4-yl)methanone]
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.00006
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(4-methoxyphenyl)methanone]
Schistosoma mansoni
-
-
0.000105
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(4-methoxyphenyl)methanone]
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.00244
(2-oxido-1,2,5-oxadiazole-3,4-diyl)bis[(4-methoxyphenyl)methanone]
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.0005
3-DAP
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.00249
4-chloro-5-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-2-phenylpyridazin-3(2H)-one
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
0.0063
4-chloro-5-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-2-phenylpyridazin-3(2H)-one
Schistosoma mansoni
-
pH 7.5, 22°C
0.00032
4-phenyl-1,2,5-oxadiazole-3-carbonitrile 2-oxide
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.00167
4-phenyl-1,2,5-oxadiazole-3-carbonitrile 2-oxide
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.0022
6-nitro-1H-1-benzothiophene-1,1-dione
Schistosoma mansoni
-
pH and temperature not specified in the publication, inhibition of GSSG reducing activity
0.0000032
auranofin
Schistosoma mansoni
-
wild type enzyme, with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.0000054
auranofin
Schistosoma mansoni
-
wild type enzyme, with GSSG as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.000007
auranofin
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.0000083
auranofin
Schistosoma mansoni
-
wild type enzyme, with thioredoxin disulfide as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.00007
aurothioglucose
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.00009
aurothiomalate
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.025
CDE16-2
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.007
CDE4
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.003
furoxan
Schistosoma mansoni
-
wild type enzyme, with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.0032
furoxan
Schistosoma mansoni
-
wild type enzyme, with GSSG as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.0054
furoxan
Schistosoma mansoni
-
wild type enzyme, with thioredoxin disulfide as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.0005
JD159
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.008
LS826
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.0025
naphthazarin
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.08
OPZ
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.012
P-1,3-benzothiazol-2-yl-N-(2-fluorophenyl)-P-phenylphosphinic amide
Schistosoma mansoni
-
-
0.0151
P-1,3-benzothiazol-2-yl-N-(2-fluorophenyl)-P-phenylphosphinic amide
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.0203
P-1,3-benzothiazol-2-yl-N-(2-fluorophenyl)-P-phenylphosphinic amide
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.000789
P-1,3-benzothiazol-2-yl-N-(5-chloropyridin-2-yl)-P-phenylphosphinic amide
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.0008
P-1,3-benzothiazol-2-yl-N-(5-chloropyridin-2-yl)-P-phenylphosphinic amide
Schistosoma mansoni
-
-
0.00154
P-1,3-benzothiazol-2-yl-N-(5-chloropyridin-2-yl)-P-phenylphosphinic amide
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.0000212
P-1,3-benzothiazol-2-yl-P-phenyl-N-1,3-thiazol-2-ylphosphinic amide
Schistosoma mansoni
-
pH 7, thioredoxin reductase activity
0.000025
P-1,3-benzothiazol-2-yl-P-phenyl-N-1,3-thiazol-2-ylphosphinic amide
Schistosoma mansoni
-
-
0.000121
P-1,3-benzothiazol-2-yl-P-phenyl-N-1,3-thiazol-2-ylphosphinic amide
Schistosoma mansoni
-
pH 7, glutathione reductase activity
0.000051
PAT
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
0.000008
potassium antimony tartrate
Schistosoma mansoni
-
wild type enzyme, with GSSG as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.000009
potassium antimony tartrate
Schistosoma mansoni
-
wild type enzyme, with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.000045
potassium antimony tartrate
Schistosoma mansoni
-
wild type enzyme, with thioredoxin disulfide as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
0.004
RMA35
Schistosoma mansoni
-
pH 7.4, 25°C, substrates: 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
1536-well based kinetic absorbance assay for thioredoxin glutathione reductase. The assay uses the catalytic reduction of DTNB by NADPH in the presence of thioredoxin glutathione reductase
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
thioredoxin glutathione reductase appears to be the major, if not the sole enzyme for these activities in adult worms, completely replacing thioredoxin reductase and glutathione reductase
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
promising drug target for the treatment of schistosomiasis
drug target
-
the enzyme is a promising drug target, as this enzyme is parasite-specific and absent in their host. A study identifies compounds with extremely potent antischistosome activity. Certain compounds are active against all major schistosomes across different life cycle stages
physiological function
physiological function
-
the enzyme plays a crucial role in maintaining redox homeostasis
physiological function
-
the enzyme of the parasite is essential for the survival of schistosomes in the mammalian host
physiological function
-
under redox pressure, schistosomes survive in mammalian hosts with the help of thioredoxin glutathione reductase
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystallization of the enzyme in complex with 1,8-naphthyridine-2 carboxylate and with the 1-(2-hydroxyethyl)piperazine derivatives, sitting drop vapor diffusion method
molecular docking of inhibitory compounds into the NADPH binding site, the active site of the thioredoxin reductase domain and the glutaredoxin active site. The most favoured binding site for all compounds is the oxidized glutathione-binding pocket of the thioredoxin reductase domain. Peptide fragments Phe505'-Leu508' and Pro572'-Thr577' play a critical role in the interactions with the inhibitors
crystal structure at 2.2 A resolution of TGR, deleted in the last two residues
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
U597C
the mutant displays significantly decreased enzyme activities compared to the wild type enzyme
C28A
-
compared to the wild type enzyme, the mutant shows 38% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 4% activity with GSSG, and 74% activity with thioredoxin disulfide
C28A/C31A
-
compared to the wild type enzyme, the mutant shows 50% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 3% activity with GSSG, and 79% activity with thioredoxin disulfide
C31A
-
compared to the wild type enzyme, the mutant shows 38% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 18% activity with GSSG, and 100% activity with thioredoxin disulfide
C31S
-
compared to the wild type enzyme, the mutant shows 100% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 129% activity with GSSG, and 105% activity with thioredoxin disulfide
C520A
-
compared to the wild type enzyme, the mutant shows 31% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 26% activity with GSSG, and 47% activity with thioredoxin disulfide
C520A/C574A
-
compared to the wild type enzyme, the mutant shows 38% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 26% activity with GSSG, and 42% activity with thioredoxin disulfide
C574A
-
compared to the wild type enzyme, the mutant shows 38% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 37% activity with GSSG, and 42% activity with thioredoxin disulfide
E330A/D334A
mutation of two key residues interacting with the inhibitor 4-aminopiazthiole. Inhibition at 0.5 mM 4-aminopiazthiole is indistinguishable from that of the wild type enzyme
E337A
mutation of E337 an interacting residue of the inhibitor indole-3-carbinol, Inhibition at 0.5 mM indole-3-carbinol is indistinguishable from that of the wild type enzyme
U597C
-
compared to the wild type enzyme, the mutant shows 25% activity with 5,5'-dithiobis(2-nitrobenzoic acid), 21% activity with GSSG, and 18% activity with thioredoxin disulfide
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
2',5'-ADP Sepharose column chromatography and Sephadex G-25 gel filtration
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli as a six-histidine tagged protein. Recombinant His-SmTGR, which would not have a penultimate selenocysteine when expressed in Escherichia coli, has no measurable activity in the insulin reduction assay
recombinant enzyme with a fused bacterial-type SECIS element is expressed in Escherichia coli strain BL21(DE3)
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
development of a cost sensitive classification model to evaluate the biological activity of inhibitors. Random forest analysis revealed 10 highly enriched scaffolds in the actives dataset. Models are evaluated using docking approaches
drug development
-
identification of inhibitory compounds facilitates further development of anti-schistosomiasis drugs with novel mechanism of action
medicine
medicine
-
identification of oxadiazole 2-oxides (TGR inhibitors) as new lead compounds for schistosomiasis chemotherapy
medicine
-
quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade, several of which are highly potent and should serve both as mechanistic tools for probing the redox balance in Schistosome mansoni, and starting points for developing medicinal leads for treatments for schistosomiasis
medicine
-
the enzyme presents a target for anti-schistosomiasis drug development
medicine
-
enzyme can be used as a diagnostic target antigen for Schistosama mansoni infection in serum and urine. Sandwich ELISA detects the protein with high diagnostic efficiency in individuals with high or low worm burden
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lea, W.A.; Jadhav, A.; Rai, G.; Sayed, A.A.; Cass, C.L.; Inglese, J.; Williams, D.L.; Austin, C.P.; Simeonov, A.
A 1,536-well-based kinetic HTS assay for inhibitors of Schistosoma mansoni thioredoxin glutathione reductase
Assay Drug Dev. Technol.
6
551-555
2008
Schistosoma mansoni
Alger, H.M.; Williams, D.L.
The disulfide redox system of Schistosoma mansoni and the importance of a multifunctional enzyme, thioredoxin glutathione reductase
Mol. Biochem. Parasitol.
121
129-139
2002
Schistosoma mansoni (Q962Y6), Schistosoma mansoni
Sayed, A.A.; Simeonov, A.; Thomas, C.J.; Inglese, J.; Austin, C.P.; Williams, D.L.
Identification of oxadiazoles as new drug leads for the control of schistosomiasis
Nat. Med.
14
407-412
2008
Schistosoma mansoni
Kuntz Angela, N.; Davioud-Charvet, E.; Sayed Ahmed, A.; Califf Lindsay, L.; Dessolin, J.; Arner Elias, S.J.; Williams David, L.
Thioredoxin glutathione reductase from Schistosoma mansoni: an essential parasite enzyme and a key drug target
PLoS Med.
4
e206
2007
Schistosoma mansoni
Simeonov, A.; Jadhav, A.; Sayed, A.A.; Wang, Y.; Nelson, M.E.; Thomas, C.J.; Inglese, J.; Williams, D.L.; Austin, C.P.
Quantitative high-throughput screen identifies inhibitors of the Schistosoma mansoni redox cascade
PLoS Negl. Trop. Dis.
2
e127
2008
Schistosoma mansoni
Angelucci, F.; Miele, A.E.; Boumis, G.; Dimastrogiovanni, D.; Brunori, M.; Bellelli, A.
Glutathione reductase and thioredoxin reductase at the crossroad: the structure of Schistosoma mansoni thioredoxin glutathione reductase
Proteins
72
936-945
2008
Schistosoma mansoni
Salinas, G.; Selkirk, M.E.; Chalar, C.; Maizels, R.M.; Fernandez, C.
Linked thioredoxin-glutathione systems in platyhelminths
Trends Parasitol.
20
340-346
2004
Echinococcus granulosus (Q869D6), Echinococcus granulosus (Q869D7), Schistosoma mansoni (Q962Y6)
Huang, H.H.; Day, L.; Cass, C.L.; Ballou, D.P.; Williams, C.H.; Williams, D.L.
Investigations of the catalytic mechanism of thioredoxin glutathione reductase from Schistosoma mansoni
Biochemistry
50
5870-5882
2011
Schistosoma mansoni
Prast-Nielsen, S.; Huang, H.H.; Williams, D.L.
Thioredoxin glutathione reductase: its role in redox biology and potential as a target for drugs against neglected diseases
Biochim. Biophys. Acta
1810
1262-1271
2011
Schistosoma mansoni (Q962Y6)
Li, T.; Ziniel, P.D.; He, P.Q.; Kommer, V.P.; Crowther, G.J.; He, M.; Liu, Q.; Van Voorhis, W.C.; Williams, D.L.; Wang, M.W.
High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis
Infect. Dis. Poverty
4
40
2015
Schistosoma mansoni
El Gendy, A.; Rabie, I.; El Deeb, S.; El Amir, A.
Importance of Schistosoma mansoni thioredoxin glutathione reductase 1- evaluation of its role in schistosomiasis diagnosis in human
J. Med. Sci.
13
635-646
2013
Schistosoma mansoni
-
Huang, J.; Hua, W.; Li, J.; Hua, Z.
Molecular docking to explore the possible binding mode of potential inhibitors of thioredoxin glutathione reductase
Mol. Med. Rep.
12
5787-5795
2015
Schistosoma japonicum (B5THG7), Schistosoma japonicum, Schistosoma mansoni (Q962Y6), Schistosoma mansoni
Gaba, S.; Jamal, S.; Drug Discovery Consortium, O.; Scaria, V.
Cheminformatics models for inhibitors of Schistosoma mansoni thioredoxin glutathione reductase
Sci. World J.
2014
957107
2014
Schistosoma mansoni
Silvestri, I.; Lyu, H.; Fata, F.; Boumis, G.; Miele, A.E.; Ardini, M.; Ippoliti, R.; Bellelli, A.; Jadhav, A.; Lea, W.A.; Simeonov, A.; Cheng, Q.; Arner, E.S.J.; Thatcher, G.R.J.; Petukhov, P.A.; Williams, D.L.; Angelucci, F.
Fragment-based discovery of a regulatory site in thioredoxin glutathione reductase acting as ''Doorstop'' for NADPH Entry
ACS Chem. Biol.
13
2190-2202
2018
Schistosoma mansoni (Q962Y6), Schistosoma mansoni
Lyu, H.; Petukhov, P.A.; Banta, P.R.; Jadhav, A.; Lea, W.A.; Cheng, Q.; Arner, E.S.J.; Simeonov, A.; Thatcher, G.R.J.; Angelucci, F.; Williams, D.L.
Characterization of lead compounds targeting the selenoprotein thioredoxin glutathione reductase for treatment of Schistosomiasis
ACS Infect. Dis.
6
393-405
2020
Schistosoma mansoni
Tripathi, T.; Chetri, P.B.
Potent inhibitors of thioredoxin glutathione reductase grail of anti-Schistosome drug within reach?
ACS Infect. Dis.
6
893-895
2020
Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium
Fata, F.; Silvestri, I.; Ardini, M.; Ippoliti, R.; Di Leandro, L.; Demitri, N.; Polentarutti, M.; Di Matteo, A.; Lyu, H.; Thatcher, G.R.J.; Petukhov, P.A.; Williams, D.L.; Angelucci, F.
Probing the surface of a parasite drug target thioredoxin glutathione reductase using small molecule fragments
ACS Infect. Dis.
7
1932-1944
2021
Schistosoma mansoni (A0A3Q0KFL1), Schistosoma mansoni
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