HOME
login
history
all enzymes
BRENDA home
History
Information on EC 1.8.1.B1 - thioredoxin glutathione reductase
for references in articles please use BRENDA:EC1.8.1.B1preliminary BRENDA-supplied EC number
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.8.1.B1 thioredoxin glutathione reductaseSpecify your search results
Word Map
- 1.8.1.B1
- schistosoma
- schistosomiasis
- mansoni
- worm
- praziquantel
- glutaredoxin
- selenocysteine
-
antischistosomal
- gssg
- auranofin
- flatworm
-
platyhelminth
-
sjtgr
- fasciola
- dtnb
- fluke
- medicine
-
hysteretic
-
oxadiazole
-
taenia
- cysticerci
-
selenocysteine-containing
-
schistosomicidal
- granulosus
-
echinococcus
- gigantica
- crassiceps
-
trematode
- furoxans
- analysis
The enzyme appears in viruses and cellular organisms
Synonyms
cTGR, DmTrxR, EgTGR, mTGR, SmTGR, TGR, thioredoxin glutathione reductase, thioredoxin-glutathione reductase, thioredoxin/glutathione reductase, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
cTGR
SmTGR
TGR
thioredoxin glutathione reductase
thioredoxin-glutathione reductase
thioredoxin/glutathione reductase
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
glutathione disulfide + NADPH + H+ = 2 glutathione + NADP+
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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'-dithio-bis(2-nitrobenzoic acid) + NADPH + H+
5'-thionitrobenzoic acid + NADP+
-
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
2-nitro-5-thiobenzoate + NADP+
-
-
-
?
beta-hydroxyethyl disulfide + NADPH + H+
2 2-sulfanylethan-1-ol + NADP+
-
-
-
-
?
cytosolic thioredoxin + NADP+
cytosolic thioredoxin disulfide + NADPH
-
-
-
-
r
glutathione-hydroxyethyl disulfide + NADPH + H+
glutathione + 2-sulfanylethan-1-ol + NADP+
-
-
-
-
?
mitochondrial thioredoxin + NADP+
mitochondrial thioredoxin disulfide + NADPH
-
-
-
-
r
thioredoxin disulfide + NADPH
thioredoxin + NADP+
-
absolute specificity for NADPH as electron donor
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
absolute specificity for NADPH as electron donor
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
glutathione disulfide + NADPH + H+
2 glutathione + NADP+
-
enzyme displays hysteretic behavior
-
-
?
GSSG + NADPH + H+
glutathione + NADP+
-
absolute specificity for NADPH as electron donor
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
Escherichia coli thioredoxin disulfide
-
-
?
additional information
?
-
-
the glutathione reductase activity of TGR exhibits hysteretic behavior regulated by the [GSSG]/[GSH] ratio. This behavior is associated with glutathionylation by GSSG and abolished by deglutathionylation
-
-
?
additional information
?
-
-
TGR promotes isomerization of disulfide bonds formed between glutathione peroxidase 4 and certain sperm proteins, generating a 46-kDa species containing glutathione peroxidase 4 from high molecular weight nonspecific cross-links
-
-
?
additional information
?
-
-
the parasite-specific enzyme thioredoxin glutathione reductase is a component of the defense system
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
?
-
-
the parasite-specific enzyme thioredoxin glutathione reductase is a component of the defense system
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
each catalytically active unit consists of three redox centers: FAD and an N-terminal Cys57/Cys62 redox-active disulfide from one monomer and a Cys489/Cys490 C-terminal redox-active disulfide from the second monomer
FAD
-
the flavin ring of FAD cofactor binds in a hydrophobic cleft formed by Cys154, Val157, Gly158, Cys159, Pro572, Phe474, and Pro443
NADPH
-
nicotinamide moiety binds up in the hydrophobic cleft formed by Val348, Ile266, Pro264,Val292, Met315, Val316, and Pro349, etc. and the diphosphate forms H-bond with Ile391, Ser318, and Arg317. The ribose sugar formes H-bonds with Arg262, Arg322, and Tyr296
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
selenium
selenium
-
glutathione reductase and thioredoxin reductase activities are dependent on the Sec-containing redox center. The activity loss caused by the Sec-to-Cys mutation can be partially compensated by a Cys-to-Sec mutation of the neighboring residue, indicating that Sec can support catalysis at this alternative position
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(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]
-
-
(3R,5R,8R) 5-(((3-carboxy-4-nitrophenyl)disulfanyl)methyl)tetrahydro-2H-thiazolo[4,3-b]thiazole-3-carboxylic acid
-
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-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
5-(((3-carboxy-4-nitrophenyl)disulfanyl)methyl) (2RS,5RS)-3,3a-dihydro-benzo[d]thiazolo[4,3-b]thiazole
-
5-bromo-N-ethyl-3,4-dinitrothiophen-2-amine
-
at 0.005 microM, 100 % larval death at 48 hours
6-methyl-2-phenoxy-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
-
-
6-nitro-1H-1-benzothiophene-1,1-dione
-
at 0.010 microM, 100 % larval death at 48 hours
NOC-7
-
i.e. 1-hydroxy-2-oxo-3-(N-3-methyl-aminopropyl)-3-methyl-1-triazene, complete inhibition at 0.1 mM
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
-
-
[mu-[1-(hydroxy-1kappaO)-2-(sulfanyl-1kappaS)pyridin-1-iumato(2-)]]-[mu-[1-(hydroxy-2kappaO)-2-(sulfanyl-1kappaS)pyridin-1-iumato(2-)]]bis(triphenylphosphane)digold
-
a single gold atom binds to Cys519 and Cys573 in the AuI-enzyme complex. 75–80% inhibition of thioredoxin and glutathione reductase activities is achieved at a 1:1 concentration ratio of inhibitor:enzyme
additional information
-
the recombinant plasmid DNA vaccine pVAX1/SjTGR lowers enzymatic activity in vivo and in vitro
-
auranofin
-
auranofin at 0.005 mg/ml (0.0074 mM) reduces 57.1% of the thioredoxin reductase activity and 71% of the glutathione reductase activity in the Schistosoma japonicum adult worms
auranofin
very potent inhibitor, nearly compete inhibition at 0.01 mM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Infections
[Study on immunologic function of thioredoxin glutathione reductase from Schistosoma japonicum].
Malaria
Investigation of a potential mechanism for the inhibition of SmTGR by Auranofin and its implications for Plasmodium falciparum inhibition.
Schistosomiasis
Characterization of Lead Compounds Targeting the Selenoprotein Thioredoxin Glutathione Reductase for Treatment of Schistosomiasis.
Schistosomiasis
Computer-Aided Drug Design for the Identification of Novel Antischistosomal Compounds.
Schistosomiasis
Fragment-Based Discovery of a Regulatory Site in Thioredoxin Glutathione Reductase Acting as "Doorstop" for NADPH Entry.
Schistosomiasis
High-throughput screening against thioredoxin glutathione reductase identifies novel inhibitors with potential therapeutic value for schistosomiasis.
Schistosomiasis
Investigations of the catalytic mechanism of thioredoxin glutathione reductase from Schistosoma mansoni.
Schistosomiasis
Mapping the catalytic cycle of Schistosoma mansoni thioredoxin glutathione reductase by X-ray crystallography.
Schistosomiasis
Proteomic profiling of nitrosative stress: protein s-oxidation accompanies s-nitrosylation.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.792
2-hydroxyethyl disulfide
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
additional information
additional information
-
kinetic properties of the Grx domain of TGR
-
0.033
5,5'-dithio-bis(2-nitrobenzoic acid)
-
mutant C574S, pH 7.0, temperature not specified in the publication
0.034
5,5'-dithio-bis(2-nitrobenzoic acid)
-
mutant C519S, pH 7.0, temperature not specified in the publication
0.038
5,5'-dithio-bis(2-nitrobenzoic acid)
-
wild-type, pH 7.0, 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
0.045
5,5'-dithiobis(2-nitrobenzoic acid)
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
0.088
5,5'-dithiobis(2-nitrobenzoic acid)
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
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
0.1451
5,5'-dithiobis(2-nitrobenzoic acid)
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
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
0.004
glutathione disulfide
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
0.0063
glutathione disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
0.012
glutathione disulfide
-
mutant C519S, pH 7.0, temperature not specified in the publication
0.013
glutathione disulfide
-
mutant C574S, pH 7.0, temperature not specified in the publication
0.015
glutathione disulfide
-
wild-type, pH 7.0, temperature not specified in the publication
0.0612
glutathione disulfide
-
pH not specified in the publication, temperature not specified in the publication
0.184
glutathione-hydroxyethyl disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
0.41
glutathione-hydroxyethyl disulfide
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
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
0.012
mitochondial thioredoxin
-
pH 7.0, 25°C, Sec-to-Cys mutant enzyme
0.0016
NADPH
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
0.01097
NADPH
-
with glutaredoxin as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
0.02142
NADPH
-
with 5,5'-dithiobis(2-nitrobenzoic acid) as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
0.048
NADPH
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
0.08324
NADPH
-
with GSSG as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
0.00324
thioredoxin disulfide
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
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
0.067
thioredoxin disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
8.65
2-hydroxyethyl disulfide
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
10.2
5,5'-dithio-bis(2-nitrobenzoic acid)
-
mutant C574S, pH 7.0, temperature not specified in the publication
12
5,5'-dithio-bis(2-nitrobenzoic acid)
-
mutant C519S, pH 7.0, temperature not specified in the publication
55
5,5'-dithio-bis(2-nitrobenzoic acid)
-
wild-type, pH 7.0, temperature not specified in the publication
1.85
5,5'-dithiobis(2-nitrobenzoic acid)
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
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
8.16
5,5'-dithiobis(2-nitrobenzoic acid)
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
12.6
5,5'-dithiobis(2-nitrobenzoic acid)
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
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
118
5,5'-dithiobis(2-nitrobenzoic acid)
-
pH 7.0, 25°C, wild-type enzyme
0.96
glutathione disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
1.62
glutathione disulfide
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
2 - 8
glutathione disulfide
-
wild-type, pH 7.0, temperature not specified in the publication
5
glutathione disulfide
-
mutant C574S, pH 7.0, temperature not specified in the publication
5.6
glutathione disulfide
-
mutant C519S, pH 7.0, temperature not specified in the publication
5.13
glutathione-hydroxyethyl disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
163.5
glutathione-hydroxyethyl disulfide
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
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
6.4
mitochondial thioredoxin
-
pH 7.0, 25°C, Sec-to-Cys mutant enzyme
1.64
NADPH
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
4.87
NADPH
-
with GSSG as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
10.92
NADPH
-
with 5,5'-dithiobis(2-nitrobenzoic acid) as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
12.6
NADPH
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
14.93
NADPH
-
with glutaredoxin as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
0.35
thioredoxin disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
3.5
thioredoxin disulfide
-
mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C
4.78
thioredoxin disulfide
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.1
2-hydroxyethyl disulfide
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
0.31
5,5'-dithio-bis(2-nitrobenzoic acid)
-
mutant C574S, pH 7.0, temperature not specified in the publication
0.35
5,5'-dithio-bis(2-nitrobenzoic acid)
-
mutant C519S, pH 7.0, temperature not specified in the publication
1.45
5,5'-dithio-bis(2-nitrobenzoic acid)
-
wild-type, pH 7.0, temperature not specified in the publication
21
5,5'-dithiobis(2-nitrobenzoic acid)
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
119
5,5'-dithiobis(2-nitrobenzoic acid)
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
2800
5,5'-dithiobis(2-nitrobenzoic acid)
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
0.38
glutathione disulfide
-
mutant C574S, pH 7.0, temperature not specified in the publication
0.47
glutathione disulfide
-
mutant C519S, pH 7.0, temperature not specified in the publication
1.87
glutathione disulfide
-
wild-type, pH 7.0, temperature not specified in the publication
150
glutathione disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
420
glutathione disulfide
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
28
glutathione-hydroxyethyl disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
390
glutathione-hydroxyethyl disulfide
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
34
NADPH
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
58.5
NADPH
-
with GSSG as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
510
NADPH
-
with 5,5'-dithiobis(2-nitrobenzoic acid) as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
1360
NADPH
-
with glutaredoxin as cosubstrate, at 25°C in 0.1 M potassium phosphate (pH 7.4)
7900
NADPH
-
mitochondrial isoform, pH 7.8, temperature not specified in the publication
5.2
thioredoxin disulfide
-
cytosolic isoform, pH 7.8, temperature not specified in the publication
1480
thioredoxin disulfide
-
at 25°C in 0.1 M potassium phosphate (pH 7.4)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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]
0.024
(3R,5R,8R) 5-(((3-carboxy-4-nitrophenyl)disulfanyl)methyl)tetrahydro-2H-thiazolo[4,3-b]thiazole-3-carboxylic acid
Echinococcus granulosus
pH 7.0, 25°C
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
-
-
0.0063
4-chloro-5-[4-(hydroxymethyl)-1H-1,2,3-triazol-1-yl]-2-phenylpyridazin-3(2H)-one
Schistosoma mansoni
-
pH 7.5, 22°C
0.014
5-(((3-carboxy-4-nitrophenyl)disulfanyl)methyl) (2RS,5RS)-3,3a-dihydro-benzo[d]thiazolo[4,3-b]thiazole
Echinococcus granulosus
pH 7.0, 25°C
0.004
6-methyl-2-phenoxy-2,3-dihydro-1,3,2-diazaphosphinin-4(1H)-one 2-oxide
Schistosoma mansoni
-
-
0.009
diethyl (3-bromo-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)propanedioate
Schistosoma mansoni
-
-
0.00008
dimethyl (3-bromo-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)propanedioate
Schistosoma mansoni
-
-
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
0.00032
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
0.0000032
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
10100
-
mitochondrial isoform, substrate 5,5'-dithiobis(2-nitrobenzoic acid), pH 7.8, temperature not specified in the publication
1091
-
after 31fold purification, using 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, at pH 7.8 and 25°C
128.5
-
crude extract, using hydroxyethyl disulfide as substrate, at pH 7.8 and 25°C
1300
-
mitochondrial isoform, substrate glutathione disulfide, pH 7.8, temperature not specified in the publication
2140
-
cytosolic isoform, substrate 5,5'-dithiobis(2-nitrobenzoic acid), pH 7.8, temperature not specified in the publication
2243
-
after 31fold purification, using hydroxyethyl disulfide as substrate, at pH 7.8 and 25°C
229
-
after 31fold purification, using GSSG as substrate, at pH 7.8 and 25°C
35
-
crude extract, using 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, at pH 7.8 and 25°C
8.11
-
with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, at pH 7.4 and 25°C
980
-
cytosolic isoform, substrate glutathione disulfide, pH 7.8, temperature not specified in the publication
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.3
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
brenda
-
tegument and tegumental cell of 2- and 4-week-old juveniles
brenda
additional information
-
no expression in caecum, muscle, and parenchyma of juvenile nor in spine and muscle of adult
brenda
-
TGR is regulated by both selenium availability and selenocysteine tRNA status. This regulation is more pronounced in liver, whereas in testes, the expression level is only slightly affected
brenda
much higher number of TGR transcripts in testis than in the rest of organs
brenda
-
TGR is not detected in the testes of a 20-day-old mouse. It is highly expressed in 7-month-old mouse testes. The enzyme accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm
brenda
-
TGR is regulated by both selenium availability and selenocysteine tRNA status. This regulation is more pronounced in liver, whereas in testes, the expression level is only slightly affected
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
mitochondrial and cytosolic variants of TGR are generated from a single TGR gene
brenda
mitochondrial and cytosolic variants of TGR are generated from a single TGR gene
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
physiological function
-
the enzyme is able to protect glutamine synthetase from oxidative inactivation, suggesting that the enzyme is competent to contend with oxidative stress
physiological function
-
the enzyme is essential for maintaining the thiol-disulfide redox homeostasis of Schistosoma japonicum
physiological function
-
the enzyme plays a crucial role in maintaining redox homeostasis
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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). F8QQF4_ECHGR
624
0
68532
TrEMBL
Mitochondrion (Reliability: 2)
Q962Y6_SCHMA
598
0
64992
TrEMBL
other Location (Reliability: 3)
TRXR3_MOUSE
652
0
71319
Swiss-Prot
other Location (Reliability: 4)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
65000
66000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
?
-
x * 65800, cytosolic isoform, x * 65800, mature mitochondrial isoform, x * 66000, SDS-PAGE of recombinant protein
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the glutathione reductase activity of TGR exhibits hysteretic behavior regulated by the [GSSG]/[GSH] ratio. This behavior is associated with glutathionylation by GSSG and abolished by deglutathionylation. TGR is glutathionylated at two Cys residues: Cys88 and Cys354 after 1 min incubation with 1 mM GSSG and NADPH. Absence of NADPH did not prevent glutathionylation
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
to 2.7 A resolution, space group of P43212, one physiological homodimer per asymmetric unit. Strucuture displays distinct binding sites for thioredoxin and the glutaredoxin domain, a single glutathione disulfide reduction site in the Grx domain, and rotation of the glutaredoxin domain toward the Sec-containing redox active site
-
modeled structure is a functional dimer, and contains a Grx domain (residues 21–83), a FAD/NADPH-binding domain or TrxR domain (residues 109–450) and a dimerization domain (residues 470–598)
-
in complex with FAD, orthorhombic space group P212121, with unit-cell parameters a 84.185, b 86.47, c 183.164 A
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
crystal structure at 2.2 A resolution of TGR, deleted in the last two residues
-
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H464Q
-
mutant enzyme has only 2% of the wild-type activity. The pH dependence of Vmax for wild-type DmTrxR has pKa values of 6.4 and 9.3 on the DmTrxR-DmTrx-2 complex, whereas H464Q DmTrxR only has an observable pKa at 6.4, indicating that the pKa at pH 9.3 is contributed mainly by His464. The pKa at pH 6.4 is assigned to Cys57 and Cys490. The thiolate on Cys490 is the nucleophile in the reduction of Trx. In contrast to wild-type DmTrxR, H464Q DmTrxR does not stabilize a thiolate-FAD charge-transfer complex in the presence of excess NADPH. The rates of steps in both the reductive and the oxidative half-reactions are markedly diminished in H464Q DmTrxR as compared to those of wild-type enzyme, indicating that His464 is involved in both half-reactions
C31S
-
the mutant has negligible deglutathionylase and GR activities when compared with wild type enzyme
C34S
-
both the deglutathionylase and GR activities of the mutant are only slightly lower when compared with wild type enzyme
C519S
-
about 30% of wild-type activity with both substrates glutathione and 5,5'-dithio-bis(2-nitrobenzoic acid)
C574S
-
about 30% of wild-type activity with both substrates glutathione and 5,5'-dithio-bis(2-nitrobenzoic acid)
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
U597C
additional information
-
analysis of TGR mutants reveales that the glutaredoxin domain is required for the glutathione reductase activity but does not affect the thioredoxin reductase activity. In contrast, both glutathione reductase and thioredoxin reductase activities are dependent on the Sec-containing redox center. The activity loss caused by the Sec-to-Cys mutation can be partially compensated by a Cys-to-Sec mutation of the neighboring residue, indicating that Sec can support catalysis at this alternative position
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
U597C
the mutant displays significantly decreased enzyme activities compared to the wild type enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
2',5'-ADP Sepharose column chromatography and Sephadex G-25 gel filtration
-
ammonium sulfate precipitation, Ni-NTA column chromatography, GSH-Sepharose column chromatography, and 2',5'-ADP-Sepharose column chromatography
DEAE-Sephacel gel filtration, hydroxyapatite chromatography column chromatography, and Cibacron blue chromatography column chromatography
-
small amounts of the soluble enzyme are obtained by purifying it from a large quantity of cells, in which protein synthesis is induced slowly for a period of 24 h at a low temperature
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cloning of two trans-spliced mRNA variants that encode thioredoxin glutathione reductases (mitochondrial and cytosolic selenocysteine-containing isoforms) that possess identical glutaredoxin and thioredoxin reductase domains and differ exclusively in their N-termini
expressed in Escherichia coli BL21 (DE3) cells
expressed in Escherichia coli BL21(DE3) cells
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
expresssion in Escherichia coli, truncated form without the last two residues Sec597Gly598
recombinant enzyme with a fused bacterial-type SECIS element is expressed in Escherichia coli strain BL21(DE3)
-
recombinant TGR is mostly insoluble when expressed in Escherichi coli, and neither cloning of the enzyme that contain various tags nor coexpression of TGR with chaperones increases its solubility
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the expression levels in 35-day-old worms and 42-day-old female worms are approximately 7times higher than the 7- and 14-day-old worms, and over 2times higher than 21- and 28-day-old worms and 42-day-old male worms
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
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
-
the enzyme is a potential target for development of novel agents against schistosomes
medicine
the enzyme is a promising target for anti Fasciola treatments
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Su, D.; Novoselov, S.V.; Sun, Q.A.; Moustafa, M.E.; Zhou, Y.; Oko, R.; Hatfield, D.L.; Gladyshev, V.N.
Mammalian selenoprotein thioredoxin/glutathione reductase: roles in disulfide bond formation and sperm maturation
J. Biol. Chem.
280
26491-26498
2005
Mus musculus
brenda
Rendon, J.L.; del Arenal, I.P.; Guevara-Flores, A.; Uribe, A.; Plancarte, A.; Mendoza-Hernandez, G.
Purification, characterization and kinetic properties of the multifunctional thioredoxin-glutathione reductase from Taenia crassiceps metacestode (cysticerci)
Mol. Biochem. Parasitol.
133
61-69
2004
Taenia crassiceps
brenda
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
brenda
Sun, Q.A.; Su, D.; Novoselov, S.V.; Carlson, B.A.; Hatfield, D.L.; Gladyshev, V.N.
Reaction mechanism and regulation of mammalian thioredoxin/glutathione reductase
Biochemistry
44
14528-14537
2005
Bos taurus, Danio rerio, Gallus gallus, Homo sapiens, Mus musculus, no activity in Caenorhabditis elegans, no activity in Canis familiaris, no activity in Drosophila melanogaster, no activity in Sus scrofa, Pan troglodytes, Rattus norvegicus, Takifugu rubripes, Xenopus laevis, Tetraodon nigroviridis
brenda
Huang, H.H.; Arscott, L.D.; Ballou, D.P.; Williams, C.H.
Acid-base catalysis in the mechanism of thioredoxin reductase from Drosophila melanogaster
Biochemistry
47
1721-1731
2008
Drosophila melanogaster
brenda
Agorio, A.; Chalar, C.; Cardozo, S.; Salinas, G.
Alternative mRNAs arising from trans-splicing code for mitochondrial and cytosolic variants of Echinococcus granulosus thioredoxin glutathione reductase
J. Biol. Chem.
278
12920-12928
2003
Echinococcus granulosus (Q869D6), Echinococcus granulosus (Q869D7), Echinococcus granulosus
brenda
Jurado, J.; Prieto-Alamo, M.J.; Madrid-Risquez, J.; Pueyo, C.
Absolute gene expression patterns of thioredoxin and glutaredoxin redox systems in mouse
J. Biol. Chem.
278
45546-45554
2003
Mus musculus (Q99MD6)
brenda
Bonilla, M.; Denicola, A.; Novoselov, S.V.; Turanov, A.A.; Protasio, A.; Izmendi, D.; Gladyshev, V.N.; Salinas, G.
Platyhelminth mitochondrial and cytosolic redox homeostasis is controlled by a single thioredoxin glutathione reductase and dependent on selenium and glutathione
J. Biol. Chem.
283
17898-17907
2008
Echinococcus granulosus
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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
brenda
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)
brenda
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
brenda
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)
brenda
Cao, Y.; Zhao, B.; Han, Y.; Zhang, J.; Li, X.; Qiu, C.; Wu, X.; Hong, Y.; Ai, D.; Lin, J.; Fu, Z.
Gene gun bombardment with DNA-coated golden particles enhanced the protective effect of a DNA vaccine based on thioredoxin glutathione reductase of Schistosoma japonicum
BioMed Res. Int.
2013
952416
2013
Schistosoma japonicum
brenda
Maggioli, G.; Silveira, F.; Martin-Alonso, J.M.; Salinas, G.; Carmona, C.; Parra, F.
A recombinant thioredoxin-glutathione reductase from Fasciola hepatica induces a protective response in rabbits
Exp. Parasitol.
129
323-330
2011
Fasciola hepatica (A8E0R8), Fasciola hepatica
brenda
Bonilla, M.; Denicola, A.; Marino, S.M.; Gladyshev, V.N.; Salinas, G.
Linked thioredoxin-glutathione systems in platyhelminth parasites: alternative pathways for glutathione reduction and deglutathionylation
J. Biol. Chem.
286
4959-4967
2011
Echinococcus granulosus
brenda
Guevara-Flores, A.; Del Arenal, I.P.; Mendoza-Hernandez, G.; Pardo, J.P.; Flores-Herrera, O.; Rendon, J.L.
Mitochondrial thioredoxin-glutathione reductase from larval Taenia crassiceps (Cysticerci)
J. Parasitol. Res.
2010
2010
2010
Taenia crassiceps
brenda
Han, Y.; Zhang, M.; Hong, Y.; Zhu, Z.; Li, D.; Li, X.; Fu, Z.; Lin, J.
Characterization of thioredoxin glutathione reductase in Schiotosoma japonicum
Parasitol. Int.
61
475-480
2012
Schistosoma japonicum (B5THG7), Schistosoma japonicum
brenda
Song, L.; Li, J.; Xie, S.; Qian, C.; Wang, J.; Zhang, W.; Yin, X.; Hua, Z.; Yu, C.
Thioredoxin glutathione reductase as a novel drug target: evidence from Schistosoma japonicum
PLoS ONE
7
e31456
2012
Schistosoma japonicum
brenda
Dobrovolska, O.; Shumilina, E.; Gladyshev, V.N.; Dikiy, A.
Structural analysis of glutaredoxin domain of Mus musculus thioredoxin glutathione reductase
PLoS ONE
7
e52914
2012
Mus musculus (Q99MD6), Mus musculus
brenda
Li, Y.; Wu, Q.; Peng, Y.; Huang, F.; Li, X.; Chen, L.; Shi, D.; Zhou, X.; Fan, X.
Expression, crystallization and preliminary X-ray diffraction analysis of thioredoxin glutathione reductase from Schistosoma japonicum in complex with FAD
Acta Crystallogr. Sect. F
70
92-96
2014
Schistosoma japonicum (Q5DE05), Schistosoma japonicum
brenda
Wu, Z.; Hou, Y.; Dai, Z.; Hu, C.A.; Wu, G.
Metabolism, nutrition, and redox signaling of hydroxyproline
Antioxid. Redox Signal.
30
674-682
2017
Echinococcus granulosus
brenda
Plancarte, A.; Nava, G.
Purification and kinetic analysis of cytosolic and mitochondrial thioredoxin glutathione reductase extracted from Taenia solium cysticerci
Exp. Parasitol.
149
65-73
2015
Taenia solium
brenda
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
brenda
Gupta, A.; Kesherwani, M.; Velmurugan, D.; Tripathi, T.
Fasciola gigantica thioredoxin glutathione reductase Biochemical properties and structural modeling
Int. J. Biol. Macromol.
89
152-160
2016
Fasciola gigantica
brenda
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
-
brenda
Saiz, C.; Castillo, V.; Fontan, P.; Bonilla, M.; Salinas, G.; Rodriguez-Haralambides, A.; Mahler, S.G.
Discovering Echinococcus granulosus thioredoxin glutathione reductase inhibitors through site-specific dynamic combinatorial chemistry
Mol. Divers.
18
1-12
2014
Echinococcus granulosus (F8QQF4), Echinococcus granulosus
brenda
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
brenda
Martinez-Gonzalez, J.J.; Guevara-Flores, A.; Rendon, J.L.; Sosa-Peinado, A.; Del Arenal Mena, I.P.
Purification and characterization of Taenia crassiceps cysticerci thioredoxin insight into thioredoxin-glutathione-reductase (TGR) substrate recognition
Parasitol. Int.
64
194-201
2015
Taenia crassiceps
brenda
Changklungmoa, N.; Kueakhai, P.; Sangpairoj, K.; Chaichanasak, P.; Jaikua, W.; Riengrojpitak, S.; Sobhon, P.; Chaithirayanon, K.
Molecular cloning and characterization of Fasciola gigantica thioredoxin-glutathione reductase
Parasitol. Res.
114
2119-2127
2015
Fasciola gigantica
brenda
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
brenda
Select items on the left to see more content.
EXTERNAL LINKS (specific for EC-Number 1.8.1.B1)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Information
