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Information on EC 1.8.1.9 - thioredoxin-disulfide reductase and Organism(s) Rattus norvegicus and UniProt Accession Q9Z0J5
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1.8.1.9 thioredoxin-disulfide reductaseIUBMB Comments
A flavoprotein (FAD).
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Word Map
- 1.8.1.9
- selenium
-
selenoproteins
- selenocysteine
- gsh
- peroxiredoxins
- dismutase
- catalase
- auranofin
- glutaredoxins
- trx1
-
selenoenzyme
- hydroperoxide
- peroxidases
- fad
- ribonucleotide
-
redox-active
- cisplatin
- dithiols
-
goldi
-
se-deficient
- dtnb
-
iodothyronine
-
flavoenzyme
- ebselen
-
redox-sensitive
-
selenium-containing
-
selenols
-
deiodinases
-
thiol-dependent
-
organoselenium
-
thioredoxin-like
-
selenium-deficient
-
se-dependent
-
n-heterocyclic
-
thioredoxin-dependent
- diselenide
-
redox-regulated
-
selenium-dependent
-
thiol-disulfide
-
thiol-based
- thioredoxin-1
- ask1
-
carbene
- 1-chloro-2,4-dinitrobenzene
- sulforaphane
-
secis
-
txnip
- trypanothione
- medicine
- analysis
- na2seo3
- agriculture
-
thioredoxin-interacting
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
thioredoxin reductase, trxr, trxr1, txnrd1, thioredoxin reductase 1, trxr2, txnrd2, thioredoxin reductase-1, thioredoxin reductase 2, nadph-dependent thioredoxin reductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
general stress protein 35
-
-
-
-
GSP35
-
-
-
-
NADP-thioredoxin reductase
-
-
-
-
NADPH-thioredoxin reductase
-
-
-
-
NADPH2:oxidized thioredoxin oxidoreductase
-
-
-
-
reductase, thioredoxin
-
-
-
-
thioredoxin reductase
thioredoxin reductase (NADPH)
-
-
-
-
thioredoxin reductase 1
TR1
TR3
TrxR
TrxR1
TrxR2
thioredoxin reductase
-
-
TrxR
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
thioredoxin:NADP+ oxidoreductase
A flavoprotein (FAD).
CAS REGISTRY NUMBER
COMMENTARY
9074-14-0
-
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
2-nitro-5-thiobenzoate + NADP
-
-
-
-
?
5,5'-dithiobis-(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
human thioredoxin + NADP+
human thioredoxin disulfide + NADPH + H+
-
-
-
-
r
thioredoxin + insulin disulfide
thioredoxin disulfide + insulin
thioredixin is the native principal substrate of TrxR1
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
2-nitro-5-thiobenzoate + NADP+
-
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
2-nitro-5-thiobenzoate + NADP+
-
i.e. DTNB
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
2-nitro-5-thiobenzoate + NADP+
-
coupled assay
-
-
?
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+
-
-
-
?
methylseleninate + H2O2
?
-
addition of selenocysteine increases the activity by 20%
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
-
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
coupled assay with DTNB
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
coupled assay, measurement of NADPH oxidation in presence of insulin and thioredoxin
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH + H+
-
in presence of NADPH, coupled assay
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
?
additional information
?
-
-
specific for NADPH, B side of nicotinamide ring
-
-
?
additional information
?
-
-
ribonucleotide reductase, thioredoxin and thioredoxin reductase constitute a system necessary for the biosynthesis of deesoxyribonucleotides
-
-
?
additional information
?
-
mitochondrial respiratory chain and thioredoxin reductase regulate intermembrane Cu,Zn-superoxide dismutase activity
-
-
?
additional information
?
-
-
the internal disulfide bond (CD7D5) of human neuroglobin can be reduced by thioredoxin reductase
-
-
?
additional information
?
-
-
ebselen, 4,4'-bistrifluoromethyl-diphenyl diselenide, 2,4,6,2',4',6-hexamethyldiphenyl diselenide, and 4,4'-biscarboxydiphenyl diselenide are no substrates
-
-
?
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
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
-
?
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
-
-
?
additional information
?
-
-
ribonucleotide reductase, thioredoxin and thioredoxin reductase constitute a system necessary for the biosynthesis of deesoxyribonucleotides
-
-
?
additional information
?
-
mitochondrial respiratory chain and thioredoxin reductase regulate intermembrane Cu,Zn-superoxide dismutase activity
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
selenium
selenocysteine
selenium
selenoprotein. TrxR1 is more sensitive to Se depletion than TrxR2, greater changes in liver than kidney. There is a prioritisation of TrxR2 over TrxR1 during Se deficiency such that TrxR1 expression is more sensitive to Se supply than TrxR2 but this sensitivity of TrxR1 is not fully accounted for by TrxR1 5' or 3'-untranslated region sequences when assessed using luciferase reporter constructs
selenium
-
the presence of a selenium atom is not chemically required to catalyze the reduction of the disulfide bond of thioredoxin
selenium
thioredoxin reductase 1 is a selenoprotein, the oxidized enzyme presents a selenenylsulfide motif in trans-configuration, with the selenium atom of selenocysteine-498 positioned beneath the side chain of Tyr-116
selenium
TrxR1 is a selenoprotein that contains a selenocysteine residue at the penultimate C-terminal
selenium
-
all three isoenzymes of mammalian TrxR contain an essential selenocysteine residue, which is the target of several drugs in cancer treatment or mercury intoxication
selenium
-
the enzyme possesses selenium in the form of selenocysteine in the active site
selenocysteine
-
contains selenocysteine as part of the redox active selenosulfide in the active center
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-aminothiazolium [trans-tetrachlorobis(2-aminothiazole)ruthenate(III)]
-
2-hydroxymethyl-5-methoxy-1-methyl-3-[(2,4,6-trifluorophenoxy)methyl]indole-4,7-dione
-
maximum inhibition is achieved 5 min after addition of 0.003 mM
2-hydroxymethyl-5-methoxy-1-methyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione
-
-
2-hydroxymethyl-6-methoxy-1-methyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione
-
-
3-(4-[[2-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)-1H-indol-1-yl]sulfonyl]phenyl)propanoic acid
-
-
3-(4-[[6-fluoro-2-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)-1H-indol-1-yl]sulfonyl]phenyl)propanoic acid
-
-
4-[6-fluoro-1-(phenylsulfonyl)-1H-indol-2-yl]-4-hydroxycyclohexa-2,5-dien-1-one
-
-
5-methoxy-1,2-dimethyl-3-[1-oxo-2-(2,4,6-trifluorophenyl)ethyl]indole-4,7-dione
-
-
chloro[N(4)-ortho-chlorophenyl-2-acetylpyridinethiosemicarbazonato]gold(III)dichloroaurate(I)
-
in addition, the complex is highly cytotoxic to MCF-7 and HT29 cells
dichloro[N(4)-ortho-chlorophenyl-2-acetylpyridinethiosemicarbazonato]antimony(III)
-
in addition, the complex is highly cytotoxic to MCF-7 and HT29 cells
ES936
-
i.e. 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione, potent inhibitor
gold
-
potent inhibitor, the inhibition of TrxR1 by the metal compound is not markedly influenced by the presence of EDTA
K2PdCl4
-
strong and irreversible inhibition, about 30% residual activity at 400 nM in the presence of NADPH, less than 10% residual activity at 400 nM for 5,5'-dithiobis(2-nitrobenzoic acid) reduction, about 90% residual activity at 400 nM for juglone reduction
K2PtCl4
-
irreversible inhibition, about 5% residual activity at 400 nM in the presence of NADPH, complete inhibition of 5,5'-dithiobis(2-nitrobenzoic acid) reduction at 400 nM, about 90% residual activity at 400 nM for juglone reduction
KAuCl4
-
irreversible inhibition, about 10% residual activity at 400 nM in the presence of NADPH, less than 5% residual activity at 400 nM for 5,5'-dithiobis(2-nitrobenzoic acid) reduction, about 70% residual activity at 400 nM for juglone reduction
methylmercury
-
in the case of methylmercury, a ratio of 16 molecules per dimer leads to a virtually inactive enzyme
palladium
-
potent inhibitor, the inhibition of TrxR1 by the metal compound is not markedly influenced by the presence of EDTA
platinum
-
the inhibition of TrxR1 by the metal compound is not markedly influenced by the presence of EDTA
reactive oxygen species
-
0.1 mM, ROS generated by xanthine/xanthine oxidase enhance the inhibitory effect of flavonoids
-
trans,trans-curcumin
-
IC50: 0.0036 mM, irreversible inhibition after incubation at room temperature for 2 h in vitro
trans-[bis(2-amino-5-methylthiazole)tetrachlororuthenate(III)]
selective inhibition of TrxR1
1-chloro-2,4-dinitrobenzene
-
TrxR inhibition by 1-chloro-2,4-dinitrobenzene results in generation of reactive oxygen species and subsequent activation of stress-inducible kinases without impairment of the cellular antioxidant status or mitochondrial function
4-hydroxy-2-nonenal
-
0.005-0.025 mM, IC50: 0.0038 mM, irreversible inhibition
auranofin
-
about 10% residual activity at 400 nM in the presence of NADPH, less than 5% residual activity at 400 nM for 5,5'-dithiobis(2-nitrobenzoic acid) reduction, about 80% residual activity at 400 nM for juglone reduction
auranofin
-
protects cerebellar granular neurons from the action of different doses of tetanus neurotoxin, about 1 microM auranofinF confers a full protection against tetnus neurotoxin intoxication. Auranofin protects cerebellar granular neurons from the cleavage of VAMP-2 induced by botulinum neurotoxi B and the cleavage of syntaxin 1A induced by botulinum neurotoxin C
cisplatin
-
i.e. cis-diamminedichloroplatinum(II), about 3% residual activity at 400 nM in the presence of NADPH, about 10% residual activity at 400 nM for 5,5'-dithiobis(2-nitrobenzoic acid) reduction, about 90% residual activity at 400 nM for juglone reduction
Hg2+
-
in the presence of NADPH, a ratio of 2 HgCl2 molecules to 1 TrxR dimer leads to a virtually inactive enzyme. On treatment with 0.005 mM selenite and NADPH, TrxR inactivated by HgCl2 displays almost full recovery of activity
additional information
-
quinols irreversible inhibit mammalian TrxR by targeting the penultimate C-terminal selenocysteine residue
-
additional information
SecTRAPs (selenium compromised thioredoxin reductase-derived apoptotic proteins) can be formed from the selenoprotein thioredoxin reductase by targeting of its selenocysteine residue with electrophiles, or by its removal through C-terminal truncation. SecTRAPs are devoid of thioredoxin reductase activity but can induce rapid cell death in cultured cancer cell lines by a gain of function. Human and rat SecTRAPs induce cell death in human A549 and HeLa cells
-
additional information
-
not inhibited by 2-methoxycinnamaldehyde and cinnamic acid after 1 h of incubation
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.5
H2O2
-
wild-type enzyme, Km-value can be reduced by addition of selenocysteine
0.0906
5,5'-dithiobis(2-nitrobenzoic acid)
mutant enzyme Y116T, in TE buffer, at 20°C
0.094
5,5'-dithiobis(2-nitrobenzoic acid)
wild type enzyme, in TE buffer, at 20°C
0.0971
5,5'-dithiobis(2-nitrobenzoic acid)
mutant enzyme Y116I, in TE buffer, at 20°C
0.139
5,5'-dithiobis(2-nitrobenzoic acid)
purified, recombinant, tetrameric enzyme
0.2156
5,5'-dithiobis(2-nitrobenzoic acid)
purified, recombinant, dimeric enzyme
0.00227
5-hydroxy-1,4-naphthoquinone
wild type enzyme, in TE buffer, at 20°C
0.00698
5-hydroxy-1,4-naphthoquinone
mutant enzyme Y116T, in TE buffer, at 20°C
0.02374
5-hydroxy-1,4-naphthoquinone
mutant enzyme Y116I, in TE buffer, at 20°C
0.00099
thioredoxin disulfide
mutant enzyme Y116I, in TE buffer, at 20°C
0.00106
thioredoxin disulfide
mutant enzyme Y116T, in TE buffer, at 20°C
0.00143
thioredoxin disulfide
wild type enzyme, in TE buffer, at 20°C
0.0032
thioredoxin disulfide
purified, recombinant, tetrameric enzyme
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
33.08
5,5'-dithiobis(2-nitrobenzoic acid)
purified, recombinant, tetrameric enzyme
47.72
5,5'-dithiobis(2-nitrobenzoic acid)
mutant enzyme Y116T, in TE buffer, at 20°C
49.87
5,5'-dithiobis(2-nitrobenzoic acid)
mutant enzyme Y116I, in TE buffer, at 20°C
70.3
5,5'-dithiobis(2-nitrobenzoic acid)
wild type enzyme, in TE buffer, at 20°C
106.3
5,5'-dithiobis(2-nitrobenzoic acid)
purified, recombinant, dimeric enzyme
24.1
5-hydroxy-1,4-naphthoquinone
wild type enzyme, in TE buffer, at 20°C
52.75
5-hydroxy-1,4-naphthoquinone
mutant enzyme Y116T, in TE buffer, at 20°C
174.3
5-hydroxy-1,4-naphthoquinone
mutant enzyme Y116I, in TE buffer, at 20°C
40.98
thioredoxin disulfide
mutant enzyme Y116I, in TE buffer, at 20°C
44.85
thioredoxin disulfide
mutant enzyme Y116T, in TE buffer, at 20°C
47 - 73
thioredoxin disulfide
purified, recombinant, tetrameric enzyme
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
183.3
5,5'-dithiobis(2-nitrobenzoic acid)
purified, recombinant, tetrameric enzyme
495
5,5'-dithiobis(2-nitrobenzoic acid)
purified, recombinant, dimeric enzyme
513.3
5,5'-dithiobis(2-nitrobenzoic acid)
mutant enzyme Y116I, in TE buffer, at 20°C
526.7
5,5'-dithiobis(2-nitrobenzoic acid)
mutant enzyme Y116T, in TE buffer, at 20°C
748.3
5,5'-dithiobis(2-nitrobenzoic acid)
wild type enzyme, in TE buffer, at 20°C
7343
5-hydroxy-1,4-naphthoquinone
mutant enzyme Y116I, in TE buffer, at 20°C
7557
5-hydroxy-1,4-naphthoquinone
mutant enzyme Y116T, in TE buffer, at 20°C
10620
5-hydroxy-1,4-naphthoquinone
wild type enzyme, in TE buffer, at 20°C
14920
thioredoxin disulfide
purified, recombinant, tetrameric enzyme
41450
thioredoxin disulfide
mutant enzyme Y116I, in TE buffer, at 20°C
42150
thioredoxin disulfide
mutant enzyme Y116T, in TE buffer, at 20°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.2
1,4-dihydroxyanthroquinone
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
1,8-dihydroxyanthroquinone
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
aloe emodin
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
aloin A
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
anthrone
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.181
chrysophanol
Rattus norvegicus
isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
frangulin A
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.049
hypericin
Rattus norvegicus
isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.132
physcion
Rattus norvegicus
isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.0079
pseudohypericin
Rattus norvegicus
isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.123
Rhein
Rattus norvegicus
isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
sennoside A
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
sennoside B
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
skyrin glucoside
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR2, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
1,4-dihydroxyanthroquinone
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
1,8-dihydroxyanthroquinone
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.0086
2-aminothiazolium [trans-tetrachlorobis(2-aminothiazole)ruthenate(III)]
Rattus norvegicus
-
0.017
2-benzoyloxycinnamaldehyde
Rattus norvegicus
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
0.0636
2-benzyloxycinnamaldehyde
Rattus norvegicus
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
0.0253
2-hydroxycinnamaldehyde
Rattus norvegicus
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
0.000146
2-hydroxymethyl-5-methoxy-1-methyl-3-[(2,4,6-trifluorophenoxy)methyl]indole-4,7-dione
Rattus norvegicus
-
in 100 mM potassium phosphate buffer, pH 7.4, at 22°C
0.1
2-pentoxycinnamaldehyde
Rattus norvegicus
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
0.0083
3-(4-[[2-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)-1H-indol-1-yl]sulfonyl]phenyl)propanoic acid
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.0098
3-(4-[[6-fluoro-2-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)-1H-indol-1-yl]sulfonyl]phenyl)propanoic acid
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.0065
4-(1,3-benzothiazol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-one
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.0761
4-(1,3-benzoxazol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-one
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.1043
4-(1-benzothien-2-yl)-4-hydroxycyclohexa-2,5-dien-1-one
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.0063
4-(5-fluoro-1,3-benzothiazol-2-yl)-4-hydroxycyclohexa-2,5-dien-1-one
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.0038
4-hydroxy-2-nonenal
Rattus norvegicus
-
0.005-0.025 mM, IC50: 0.0038 mM, irreversible inhibition
0.0029
4-hydroxy-4-[1-(phenylsulfonyl)-1H-indol-2-yl]cyclohexa-2,5-dien-1-one
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.0027
4-[6-fluoro-1-(phenylsulfonyl)-1H-indol-2-yl]-4-hydroxycyclohexa-2,5-dien-1-one
Rattus norvegicus
-
pH 7.5, determined after 60 min incubation of recombinant rat TrxR with 5,5'-dithiobis(2-nitrobenzoic acid) as substrate, irreversible
0.007
5-fluoro-2-hydroxycinnamaldehyde
Rattus norvegicus
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
0.000082
5-methoxy-1,2-dimethyl-3-[1-oxo-2-(2,4,6-trifluorophenyl)ethyl]indole-4,7-dione
Rattus norvegicus
-
in 100 mM potassium phosphate buffer, pH 7.4, at 22°C
0.18
aloe emodin
Rattus norvegicus
isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
aloin A
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
anthrone
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.00023
chloro[N(4)-ortho-chlorophenyl-2-acetylpyridinethiosemicarbazonato]gold(III)dichloroaurate(I)
Rattus norvegicus
-
pH 7.0, 37°C
0.194
chrysophanol
Rattus norvegicus
isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.00016
dichloro[N(4)-ortho-chlorophenyl-2-acetylpyridinethiosemicarbazonato]antimony(III)
Rattus norvegicus
-
pH 7.0, 37°C
0.2
frangulin A
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.198
hypericin
Rattus norvegicus
isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.185
physcion
Rattus norvegicus
isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.0046
pseudohypericin
Rattus norvegicus
isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.084
Rhein
Rattus norvegicus
isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
sennoside A
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
sennoside B
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.2
skyrin glucoside
Rattus norvegicus
IC50 above 0.2 mM, isoform TrxR1, at 25°C in 0.2 M Na, K-phosphate buffer (pH 7.4)
0.0036
trans,trans-curcumin
Rattus norvegicus
-
IC50: 0.0036 mM, irreversible inhibition after incubation at room temperature for 2 h in vitro
0.0713
trans-cinnamaldehyde
Rattus norvegicus
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
TGF-betA1-treatment up-regulated thioredoxin reductase 1
lead exposure causes a marked increase in the thioredoxin reductase-1 activity in the kidney of rats. This is the only parameter affected by low lead doses both after acute and chronic exposure
-
Abeta-resistant PC-12 cells display higher levels of thioredoxin and thioredoxin reductase
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
-
inhibition of mitochondrial thioredoxin reductase leads to oxidation of downstream enzymes such as thioredoxin and peroxiredoxin
malfunction
-
Txnrd1 knock-out cells cannot be rescued from glutathione depletion-induced cell death either by antioxidants, xCT overexpression, or co-culturing with xCT-overexpressing cells that condition the medium with Cys
physiological function
-
glutathione deficiency can be rescued by forced expression of xCT (the substrate-specific subunit of the cystine/glutamate antiporter), which additionally requires the presence of functional isoform Txnrd1, but not isoform Txnrd2
physiological function
-
the thioredoxin system has a large number of functions in DNA synthesis, defense against oxidative stress and apoptosis or redox signaling with reference to many diseases
physiological function
-
the thioredoxin system, comprising thioredoxin, thioredoxin reductase, and NADPH, is critical for cellular stress response, protein repair, and protection against oxidative damage
physiological function
-
the thioredoxin system plays a major role in releasing the L chain of tetanus neurotoxin and botulinum neurotoxins after their translocation across the membrane of the endocytic vesicle
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). TRXR2_RAT
526
0
56575
Swiss-Prot
Mitochondrion (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
54386
2 * 54386, highly active enzyme form, calculated from amino acid sequence
55000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
homodimer
2 * 54386, highly active enzyme form, calculated from amino acid sequence
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
in the presence of 10 mM NADP+, hanging drop vapor diffusion method, using 15% polyethylene glycol 3350, 12% ethylene glycol, and 0.1 M HEPES, pH 7.5
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SCCS
mutant with flanking serine residues introduced into the C-terminal tetrapeptide of the wild type enzyme, less than 0.5% activity of the wild type enzyme
SeC498C
-
antisense technique, exchange in the catalytic active selenosulfide at the C-terminus, resulting in higher pH-optimum, 100fold lower turnover number, 10fold lower Km-value, no activity with H2O2
Y116I
additional information
-
truncated enzyme mutant without catalytic active C-terminus
Y116I
the mutation decreases sensitivity to inhibition by cisplatin and lowers catalytic efficiency in reduction of thioredoxin compared to the wild type enzyme
Y116I
the mutation decreases sensitivity to inhibition by cisplatin, lowers catalytic efficiency in reduction of thioredoxin, and increases turnover using 5-hydroxy-1,4-naphthoquinone (juglone) as substrate compared to the wild type enzyme
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
2',5'-ADP Sepharose column chromatography and phenylarsine oxide Sepharose column chromatography
2',5'-ADP Sepharose column chromatography and phenylarsine oxide-Sepharose column chroamtography
ammonium sulfate precipitation, DEAE-Sephacel gel filtration, 2',5'-ADP-Sepharose 4B affinity chromatography, and omega-aminohexyl-Sepharose 4B column chromatography
-
HisBind HiTrap metal-affinity column chromatography, 2',5'-ADP-Sepharose column chromatography, and CNBr-activated Sepharose column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
overexpression of antisense mutant in Escherichia coli, expression of wild-type in COS-7 cells, amino acid sequence analysis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
thioredoxin reductase-1 may be an early indicator of acute exposure to low lead doses
medicine
medicine
-
inhibition of thioredoxin reductase represents a potential target in pancreatic cancer and provides a biomarker of effect of lead indolequinones in this type of cancer
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Luthman, M.; Holmgren, A.
Rat liver thioredoxin and thioredoxin reductase: purification and characterization
Biochemistry
21
6628-6633
1982
Rattus norvegicus
Larsson, A.
Thioredoxin reductase from rat liver
Eur. J. Biochem.
35
346-349
1973
Rattus norvegicus
Zhong, L.; Holmgren, A.
Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations
J. Biol. Chem.
275
18121-18128
2000
Rattus norvegicus
Sun, Q.A.; Zappacosta, F.; Factor, V.M.; Wirth, P.J.; Hatfield, D.L.; Gladyshev, V.N.
Heterogeneity within animal thioredoxin reductases. Evidence for alternative first exon splicing
J. Biol. Chem.
276
3106-3114
2001
Drosophila melanogaster, Drosophila melanogaster (P91938), Homo sapiens, Homo sapiens (Q9NNW7), Mus musculus, Mus musculus (Q9JMH6), Rattus norvegicus
Xia, L.; Nordman, T.; Olsson, J.M.; Damdimopoulos, A.; Bjorkhem-Bergman, L.; Nalvarte, I.; Eriksson, L.C.; Arner, E.S.; Spyrou, G.; Bjornstedt, M.
The mammalian cytosolic selenoenzyme thioredoxin reductase reduces ubiquinone. A novel mechanism for defense against oxidative stress
J. Biol. Chem.
278
2141-2146
2003
Bos taurus, Escherichia coli, Homo sapiens, Rattus norvegicus
Lu, J.; Papp, L.V.; Fang, J.; Rodriguez-Nieto, S.; Zhivotovsky, B.; Holmgren, A.
Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity
Cancer Res.
66
4410-4418
2006
Rattus norvegicus
Cassidy, P.B.; Edes, K.; Nelson, C.C.; Parsawar, K.; Fitzpatrick, F.A.; Moos, P.J.
Thioredoxin reductase is required for the inactivation of tumor suppressor p53 and for apoptosis induced by endogenous electrophiles
Carcinogenesis
27
2538-2549
2006
Rattus norvegicus
Johansson, L.; Arscott, L.D.; Ballou, D.P.; Williams, C.H.; Arner, E.S.
Studies of an active site mutant of the selenoprotein thioredoxin reductase: the Ser-Cys-Cys-Ser motif of the insect orthologue is not sufficient to replace the Cys-Sec dyad in the mammalian enzyme
Free Radic. Biol. Med.
41
649-656
2006
Rattus norvegicus (O89049)
Fang, J.; Holmgren, A.
Inhibition of thioredoxin and thioredoxin reductase by 4-hydroxy-2-nonenal in vitro and in vivo
J. Am. Chem. Soc.
128
1879-1885
2006
Rattus norvegicus
Fang, J.; Lu, J.; Holmgren, A.
Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity
J. Biol. Chem.
280
25284-25290
2005
Homo sapiens, Rattus norvegicus
Omata, Y.; Folan, M.; Shaw, M.; Messer, R.L.; Lockwood, P.E.; Hobbs, D.; Bouillaguet, S.; Sano, H.; Lewis, J.B.; Wataha, J.C.
Sublethal concentrations of diverse gold compounds inhibit mammalian cytosolic thioredoxin reductase (TrxR1)
Toxicol. In Vitro
20
882-890
2006
Rattus norvegicus
Crosley, L.K.; Meplan, C.; Nicol, F.; Rundloef, A.K.; Arner, E.S.; Hesketh, J.E.; Arthur, J.R.
Differential regulation of expression of cytosolic and mitochondrial thioredoxin reductase in rat liver and kidney
Arch. Biochem. Biophys.
459
178-188
2007
Rattus norvegicus (O89049), Rattus norvegicus Rowett (O89049)
Conterato, G.M.; Augusti, P.R.; Somacal, S.; Einsfeld, L.; Sobieski, R.; Torres, J.R.; Emanuelli, T.
Effect of lead acetate on cytosolic thioredoxin reductase activity and oxidative stress parameters in rat kidneys
Basic Clin. Pharmacol. Toxicol.
101
96-100
2007
Rattus norvegicus (O89049)
Seyfried, J.; Wuellner, U.
Inhibition of thioredoxin reductase induces apoptosis in neuronal cell lines: role of glutathione and the MKK4/JNK pathway
Biochem. Biophys. Res. Commun.
359
759-764
2007
Rattus norvegicus
Inarrea, P.; Moini, H.; Han, D.; Rettori, D.; Aguilo, I.; Alava, M.A.; Iturralde, M.; Cadenas, E.
Mitochondrial respiratory chain and thioredoxin reductase regulate intermembrane Cu,Zn-superoxide dismutase activity: implications for mitochondrial energy metabolism and apoptosis
Biochem. J.
405
173-179
2007
Rattus norvegicus (O89049)
Park, S.M.; Jung, J.S.; Jang, M.S.; Kang, K.S.; Kang, S.K.
Transforming growth factor-beta1 regulates the fate of cultured spinal cord-derived neural progenitor cells
Cell Prolif.
41
248-264
2008
Rattus norvegicus (O89049)
Chew, E.H.; Lu, J.; Bradshaw, T.D.; Holmgren, A.
Thioredoxin reductase inhibition by antitumor quinols: a quinol pharmacophore effect correlating to antiproliferative activity
FASEB J.
22
2072-2083
2008
Rattus norvegicus
Trandafir, F.; Hoogewijs, D.; Altieri, F.; Rivetti di Val Cervo, P.; Ramser, K.; Van Doorslaer, S.; Vanfleteren, J.R.; Moens, L.; Dewilde, S.
Neuroglobin and cytoglobin as potential enzyme or substrate
Gene
398
103-113
2007
Rattus norvegicus
Cumming, R.C.; Dargusch, R.; Fischer, W.H.; Schubert, D.
Increase in expression levels and resistance to sulfhydryl oxidation of peroxiredoxin isoforms in amyloid beta-resistant nerve cells
J. Biol. Chem.
282
30523-30534
2007
Rattus norvegicus
Mura, P.; Camalli, M.; Bindoli, A.; Sorrentino, F.; Casini, A.; Gabbiani, C.; Corsini, M.; Zanello, P.; Rigobello, M.P.; Messori, L.
Activity of rat cytosolic thioredoxin reductase is strongly decreased by trans-[bis(2-amino-5-methylthiazole)tetrachlororuthenate(III)]: first report of relevant thioredoxin reductase inhibition for a ruthenium compound
J. Med. Chem.
50
5871-5874
2007
Rattus norvegicus (O89049)
Reyes, D.Y.; Zuber, P.
Activation of transcription initiation by Spx: formation of transcription complex and identification of a Cis-acting element required for transcriptional activation
Mol. Microbiol.
69
765-779
2008
Rattus norvegicus (O89049), Homo sapiens (Q16881)
Anestal, K.; Prast-Nielsen, S.; Cenas, N.; Arner, E.S.
Cell death by SecTRAPs: thioredoxin reductase as a prooxidant killer of cells
PLoS ONE
3
e1846
2008
Homo sapiens, Rattus norvegicus (O89049)
Lacey, B.M.; Eckenroth, B.E.; Flemer, S.; Hondal, R.J.
Selenium in thioredoxin reductase: a mechanistic perspective
Biochemistry
47
12810-12821
2008
Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus, Rattus norvegicus
Rengby, O.; Cheng, Q.; Vahter, M.; Joernvall, H.; Arner, E.S.
Highly active dimeric and low-activity tetrameric forms of selenium-containing rat thioredoxin reductase 1
Free Radic. Biol. Med.
46
893-904
2009
Rattus norvegicus (O89049)
Eriksson, S.E.; Prast-Nielsen, S.; Flaberg, E.; Szekely, L.; Arner, E.S.
High levels of thioredoxin reductase 1 modulate drug-specific cytotoxic efficacy
Free Radic. Biol. Med.
47
1661-1671
2009
Rattus norvegicus (O89049), Homo sapiens (Q16881), Homo sapiens
Chew, E.H.; Nagle, A.A.; Zhang, Y.; Scarmagnani, S.; Palaniappan, P.; Bradshaw, T.D.; Holmgren, A.; Westwell, A.D.
Cinnamaldehydes inhibit thioredoxin reductase and induce Nrf2: potential candidates for cancer therapy and chemoprevention
Free Radic. Biol. Med.
48
98-111
2010
Escherichia coli, Homo sapiens, Rattus norvegicus
Cheng, Q.; Sandalova, T.; Lindqvist, Y.; Arner, E.S.
Crystal structure and catalysis of the selenoprotein thioredoxin reductase 1
J. Biol. Chem.
284
3998-4008
2009
Rattus norvegicus (O89049)
Hondal, R.J.; Ruggles, E.L.
Differing views of the role of selenium in thioredoxin reductase
Amino Acids
41
73-89
2011
Mus musculus, Rattus norvegicus
Holmgren, A.; Lu, J.
Thioredoxin and thioredoxin reductase: current research with special reference to human disease
Biochem. Biophys. Res. Commun.
396
120-124
2010
Rattus norvegicus
Turanov, A.A.; Kehr, S.; Marino, S.M.; Yoo, M.H.; Carlson, B.A.; Hatfield, D.L.; Gladyshev, V.N.
Mammalian thioredoxin reductase 1: roles in redox homoeostasis and characterization of cellular targets
Biochem. J.
430
285-293
2010
Mus musculus, Rattus norvegicus (O89049), Homo sapiens (Q16881)
Singh, D.V.; Misra, K.
Curcuminoids as inhibitors of thioredoxin reductase: a receptor based pharmacophore study with distance mapping of the active site
Bioinformation
4
187-192
2009
Rattus norvegicus
Sorrentino, F.; Karioti, A.; Gratteri, P.; Rigobello, M.P.; Scutari, G.; Messori, L.; Bindoli, A.; Chioccioli, M.; Gabbiani, C.; Bergonzi, M.C.; Bilia, A.R.
Hypericins and thioredoxin reductase: Biochemical and docking studies disclose the molecular basis for effective inhibition by naphthodianthrones
Bioorg. Med. Chem.
19
631-641
2011
Rattus norvegicus (O89049), Rattus norvegicus (Q9Z0J5)
Carvalho, C.M.; Lu, J.; Zhang, X.; Arner, E.S.; Holmgren, A.
Effects of selenite and chelating agents on mammalian thioredoxin reductase inhibited by mercury: implications for treatment of mercury poisoning
FASEB J.
25
370-381
2011
Homo sapiens, Rattus norvegicus
Prast-Nielsen, S.; Cebula, M.; Pader, I.; Arner, E.S.
Noble metal targeting of thioredoxin reductase--covalent complexes with thioredoxin and thioredoxin-related protein of 14 kDa triggered by cisplatin
Free Radic. Biol. Med.
49
1765-1778
2010
Homo sapiens, Rattus norvegicus
Mandal, P.K.; Seiler, A.; Perisic, T.; Koelle, P.; Banjac Canak, A.; Foerster, H.; Weiss, N.; Kremmer, E.; Lieberman, M.W.; Bannai, S.; Kuhlencordt, P.; Sato, H.; Bornkamm, G.W.; Conrad, M.
System x(c)- and thioredoxin reductase 1 cooperatively rescue glutathione deficiency
J. Biol. Chem.
285
22244-22253
2010
Rattus norvegicus
Rigobello, M.P.; Bindoli, A.
Mitochondrial thioredoxin reductase purification, inhibitor studies, and role in cell signaling
Methods Enzymol.
474
109-122
2010
Rattus norvegicus
Turanov, A.A.; Hatfield, D.L.; Gladyshev, V.N.
Characterization of protein targets of mammalian thioredoxin reductases
Methods Enzymol.
474
245-254
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Yan, C.; Shieh, B.; Reigan, P.; Zhang, Z.; Colucci, M.A.; Chilloux, A.; Newsome, J.J.; Siegel, D.; Chan, D.; Moody, C.J.; Ross, D.
Potent activity of indolequinones against human pancreatic cancer: identification of thioredoxin reductase as a potential target
Mol. Pharmacol.
76
163-172
2009
Homo sapiens, Rattus norvegicus
de Freitas, A.S.; Rocha, J.B.
Diphenyl diselenide and analogs are substrates of cerebral rat thioredoxin reductase: a pathway for their neuroprotective effects
Neurosci. Lett.
503
1-5
2011
Rattus norvegicus
Parrilha, G.L.; Ferraz, K.S.; Lessa, J.A.; de Oliveira, K.N.; Rodrigues, B.L.; Ramos, J.P.; Souza-Fagundes, E.M.; Ott, I.; Beraldo, H.
Metal complexes with 2-acetylpyridine-N(4)-orthochlorophenylthiosemicarbazone cytotoxicity and effect on the enzymatic activity of thioredoxin reductase and glutathione reductase
Eur. J. Med. Chem.
84
537-544
2014
Rattus norvegicus
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