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Information on EC 1.8.1.9 - thioredoxin-disulfide reductase and Organism(s) Escherichia coli and UniProt Accession P0A9P4
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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: Escherichia coli
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 (NADPH)
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
thioredoxin + NADP+ = thioredoxin disulfide + NADPH + H+
catalytic mechanism
-
thioredoxin + NADP+ = thioredoxin disulfide + NADPH + H+
inhibition mechanism
-
thioredoxin + NADP+ = thioredoxin disulfide + NADPH + H+
oxidation-reduction cycle of thioredoxin
-
thioredoxin + NADP+ = thioredoxin disulfide + NADPH + H+
2 conformations possible, termed FR and FO conformation, which differ in their fluorescence spectroscopic behaviour, their accessibility for inhibitors and in the efficiency of electron transfer to FAD, involving position 138 in the wild-type and the mutant C138S
-
thioredoxin + NADP+ = thioredoxin disulfide + NADPH + H+
electron transfer in the enzyme complex of apoenzyme, FAD and thioredoxin with NADPH
-
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
thioredoxin disulfide + insulin
thioredoxin + insulin disulfide
-
-
-
?
5,5'-dithiobis-(2-nitrobenzoic acid) + NADPH + H+
2-nitro-5-thiobenzoate + NADP+
-
-
-
-
?
protein disulfide isomerase like protein 1 + NADPH
protein disulfide isomerase like protein 1 + NADP+
-
protein disulfide isomerase like protein 1 from rat liver containing a thioredoxin domain
protein disulfide isomerase like protein 1 with reduced disulfides, coupled assay with insulin
?
protein disulfide isomerase like protein 2 + NADPH
protein disulfide isomerase like protein 2 + NADP+
-
protein disulfide isomerase like protein 2 from rat liver containing a thioredoxin domain
protein disulfide isomerase like protein 2 with reduced disulfides, coupled assay with insulin
?
thioredoxin + 3-acetylpyridine adenine dinucleotide
thioredoxin disulfide + reduced 3-acetylpyridine adenine dinucleotide
-
wild-type enzyme, mutant enzyme C135S and thioredoxin in subunit complex C135-C32S with the enzyme
-
?
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+
-
requires thioredoxin for reduction of DTNB
-
-
?
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH
2-nitro-5-thiobenzoate + NADP+
-
coupled assay
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
wide variety of electron acceptors
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
coupled assay with DTNB
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
coupled assay with DTNB
-
r
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
coupled assay, measurement of NADPH oxidation in presence of insulin and thioredoxin
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
NADH in the standard assay, wild-type and chimeric mutants with and without amino acid exchanges
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
substrate e.g. thioredoxin disulfide from phage T4
-
r
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
metabolic function of thioredoxin reductase-thioredoxin system: supplies reducing equivalents for a wide variety of acceptors, e.g. : ribonucleotide reductase, nonspecific protein disulfide reductase, methionine sulfoxide reductase, D-proline reductase
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH + H+
-
in presence of NADPH, coupled assay
-
ir
thioredoxin + NADP+
thioredoxin disulfide + NADPH + H+
-
in presence of NADPH, coupled assay
-
r
thioredoxin + NADP+
thioredoxin disulfide + NADPH + H+
-
i.e. DTNB
-
ir
thioredoxin disulfide + NADPH + H+
thioredoxin + NADP+
-
the active site of Escherichia coli thioredoxin reductase contains a CATC motif without any selenocysteine and it specifically reduces oxidized Escherichia coli thioredoxin
-
-
?
additional information
?
-
R73G, R73D, and K36A site-directed mutants of thioredoxin are impaired to different extents in their ability to be reduced by TrxR
-
-
?
additional information
?
-
-
R73G, R73D, and K36A site-directed mutants of thioredoxin are impaired to different extents in their ability to be reduced by TrxR
-
-
?
additional information
?
-
-
reduction of thioredoxin by NADPH is virtually complete, equilibrium constant is 48 at pH 7
-
-
?
additional information
?
-
-
slowly reduces other proteins, e.g. insulin, lipoate and ribonuclease
-
-
?
additional information
?
-
-
redox system for electron transfer in the complex of apoenzyme, FAD and thioredoxin with NADPH or other electron acceptors
-
-
?
additional information
?
-
-
redox system for electron transfer in the complex of apoenzyme, FAD and thioredoxin with NADPH or other electron acceptors
-
-
?
additional information
?
-
-
thioredoxin reductase is essential for formate dehydrogenase H production and for labelling the formate dehydrogenase H polypeptide with 75Se-selenite
-
-
?
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
?
-
-
thioredoxin reductase is essential for formate dehydrogenase H production and for labelling the formate dehydrogenase H polypeptide with 75Se-selenite
-
-
?
thioredoxin + NADP+
thioredoxin disulfide + NADPH
-
metabolic function of thioredoxin reductase-thioredoxin system: supplies reducing equivalents for a wide variety of acceptors, e.g. : ribonucleotide reductase, nonspecific protein disulfide reductase, methionine sulfoxide reductase, D-proline reductase
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
-
-
FAD
-
wild-type and chimeric mutants partly from Salmonella typhimurium AhpF protein
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,2'-(ethane-1,2-diyl)di(1,2-benzoselenazol-3(2H)-one)
-
IC50 value for HEK-293T cells 3.4 microg/ml
2,2'-(hexane-1,6-diyl)di(1,2-benzoselenazol-3(2H)-one)
-
IC50 value for HEK-293T cells 2.5 microg/ml
phenyl mercuric acetate
-
stabilizes enzyme in one of two possible conformations
additional information
-
not inhibited by trans-cinnamaldehyde and 2-hydroxycinnamaldehyde after 1 h of incubation
-
ebselen
-
reversible competitive inhibitor of the enzyme from Escherichia coli. Ebselen can form a stable selenosulfide bond with the attacking cysteine in Escherichia coli thioredoxin reductase which cannot easily be resolved by the other cysteine in the active site. The binding blocks the electron transfer from Escherichia coli TrxR to Trx, and ultimately to the downstream substrates of thioredoxin. Ebselen is an excellent substrate for mammalian thioredoxin system
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0275
ebsulfur disulfide
-
pH 7.5, temperature not specified in the publication
additional information
additional information
-
Km-values are pH-dependent
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
50.3
DTNB
-
chimeric enzyme mutant, partly from Salmonella typhimurium AhpF protein
1.7
ebsulfur disulfide
-
pH 7.5, temperature not specified in the publication
additional information
additional information
-
wild-type and recombinant chimeric mutants in a coupled assay
-
additional information
additional information
-
transhydrogenase activity of mutants and wild-type enzyme with thioredoxin and FAD
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
60.5
ebsulfur disulfide
-
pH 7.5, temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00005
2,2'-(ethane-1,2-diyl)di(1,2-benzoselenazol-3(2H)-one)
-
pH 7.5, temperature not specified in the publication
0.00001
2,2'-(hexane-1,6-diyl)di(1,2-benzoselenazol-3(2H)-one)
-
pH 7.5, temperature not specified in the publication
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0994
2-benzoyloxycinnamaldehyde
Escherichia coli
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
0.0844
5-fluoro-2-hydroxycinnamaldehyde
Escherichia coli
-
1 h incubation with recombinant TrxR, in TE buffer, at 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
wild-type and chimeric mutants with and without amino acid exchanges
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
-
ebselen as an inhibitor of thiol-dependent enzymes in pathogens
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
73000 - 75000
-
amino acid analysis based on 2 mol FAD per molecule of enzyme
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C135S
C135S/C32S
-
via the active disulfide centers a subunit complex of tightly bound enzyme, C135 and C138, and thioredoxin, C32 and C35, is formed, exchange of one cysteine for one serine in each protein by site-directed mutagenesis, conformation analysis
C135S/C35S
-
fluorescence spectroscopic investigation of the interaction with the flavin group
C138S
C138S/C35S
-
fluorescence spectroscopic investigation of the interaction with the flavin group
C32S
C35S
additional information
C135S
-
fluorescence spectroscopic investigation of the interaction with the flavin group
C135S
-
exchange of 1 cysteine in the active center disulfide, 1 cysteine at position 138 is remaining
C138S
-
fluorescence spectroscopic investigation of the interaction with the flavin group
C138S
-
exchange of 1 cysteine in the active center disulfide, 1 cysteine at position 135 is remaining, very low activity
C32S
-
fluorescence spectroscopic investigation of the interaction with the flavin group
C32S
-
exchange of 1 cysteine in the active center disulfide, 1 cysteine at position 35 is remaining, low activity
C35S
-
fluorescence spectroscopic investigation of the interaction with the flavin group
C35S
-
exchange of 1 cysteine in the active center disulfide, 1 cysteine at position 32 is remaining
additional information
-
trxB gene is combined to chimeric enzyme NT-TrR by exchanging the N-terminus of Escherichia coli with the N-terminus of Salmonella typhimurium AhpF gene protein, which encodes a protein with about 35% homology in the N-terminal region, 2 other mutants are constructed in the same way but with double mutation C129S/C132S and C342S/C345S, the first in the Escherichia coli part and the latter in the Salmonella part of the chimeric protein, activity corressponding to organism wild-type giving the N-terminal part, except for C342S/C345S chimeric mutant who has no activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme-thioredoxin subunit complex C135-C32 and mutant S135-S32
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of wild-type and mutant enzymes from plasmids
-
subunit complex of enzyme via C135 with thioredoxin C32, mutant complex S135-S32, expression from plasmid
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Williams, C.H.
Flavin-containing dehydrogenases
The Enzymes, 3rd Ed. (Boyer, P. D. , ed. )
13
89-173
1976
Escherichia coli
-
Pigiet, V.P.; Conley, R.R.
Purification of thioredoxin, thioredoxin reductase, and glutathione reductase by affinity chromatography
J. Biol. Chem.
252
6367-6372
1977
Escherichia coli
Lundstrm, J.; Holmgren, A.
Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity
J. Biol. Chem.
265
9114-9120
1990
Bos taurus, Escherichia coli
Gleason, F.K.; Lim, C.J.; Gerami-Nejad, M.; Fuchs, J.A.
Characterization of Escherichia coli thioredoxins with altered active site residues
Biochemistry
29
3701-3709
1990
Escherichia coli
Schallreuter, K.U.; Pittelkow, M.R.; Wood, J.M.
EF-Hands calcium binding regulates the thioredoxin reductase/thioredoxin electron transfer in human keratinocytes
Biochem. Biophys. Res. Commun.
162
1311-1316
1989
Escherichia coli, Homo sapiens
Prongay, A.J.; Engelke, D.R.; Williams, C.H.
Characterization of two active site mutations of thioredoxin reductase from Escherichia coli [published erratum appears in J Biol Chem 1989 Jul 15;264(20):12113]
J. Biol. Chem.
264
2656-2664
1989
Escherichia coli
Russel, M.; Model, P.
Direct cloning of the trxB gene that encodes thioredoxin reductase
J. Bacteriol.
163
238-242
1985
Escherichia coli
O'Donnell, M.E.; Williams, C.H.
Reaction of both active site thiols of reduced thioredoxin reductase with N-ethylmaleimide
Biochemistry
24
7617-7621
1985
Escherichia coli
Grankvist, K.; Holmgren, A.; Luthman, M.; Tljedal, I.B.
Thioredoxin and thioredoxin reductase in pancreatic islets may participate in diabetogenic free-radical production
Biochem. Biophys. Res. Commun.
107
1412-1418
1982
Bos taurus, Escherichia coli, Mus musculus
Berglund, O.; Holmgren, A.
Thioredoxin reductase-mediated hydrogen transfer from Escherichia coli thioredoxin-(SH)2 to phage T4 thioredoxin-S2
J. Biol. Chem.
250
2778-2782
1975
Escherichia coli
Moore, E.C.; Reichard, P.; Thelander, L.
Enzymatic synthesis of desoxyribonucleotides. V. Purification and properties of thioredoxin reductase from Escherichia coli B
J. Biol. Chem.
239
3445-3452
1964
Escherichia coli
Lennon, B.W.; Williams, C.H., Jr.
Enzyme-monitored turnover of Escherichia coli thioredoxin reductase: insights for catalysis
Biochemistry
35
4704-4712
1996
Escherichia coli
Wang, P.F.; Veine, D.M.; Ahn, S.H.; Williams, C.H., Jr.
A stable mixed disulfide between thioredoxin reductase and its substrate, thioredoxin: preparation and characterization
Biochemistry
35
4812-4819
1996
Escherichia coli
Veine, D.M.; Mulrooney, S.B.; Wang, P.F.; Williams, C.H., Jr.
Formation and properties of mixed disulfides between thioredoxin reductase from Escherichia coli and thioredoxin: evidence that cysteine-138 functions to initiate dithiol-disulfide interchange and to accept the reducing equivalent from reduced flavin
Protein Sci.
7
1441-1450
1998
Escherichia coli
Van den Berg, P.A.W.; Mulrooney, S.B.; Gobets, B.; van Stokkum, I.H.M.; van Hoek, A.; Williams, C.H., Jr.; Visser, A.J.W.G.
Exploring the conformational equilibrium of E. coli thioredoxin reductase: characterization of two catalytically important states by ultrafast flavin fluorescence spectroscopy
Protein Sci.
10
2037-2049
2001
Escherichia coli
Reynolds, C.M.; Poole, L.B.
Attachment of the N-terminal domain of Salmonella typhimurium AhpF to Escherichia coli thioredoxin reductase confers AhpC reductase activity but does not affect thioredoxin reductase activity
Biochemistry
39
8859-8869
2000
Escherichia coli
Lundstroem-Ljung, J.; Birnbach, U.; Rupp, K.; Soeling, H.D.; Holmgren, A.
Two resident ER-proteins, CaBP1 and CaBP2, with thioredoxin domains, are substrates for thioredoxin reductase: comparison with protein disulfide isomerase
FEBS Lett.
357
305-308
1995
Escherichia coli
Watabe, S.; Makino, Y.; Ogawa, K.; Hiroi, T.; Yamamoto, Y.; Takahashi, S.Y.
Mitochondrial thioredoxin reductase in bovine adrenal cortex its purification, properties, nucleotide/amino acid sequences, and identification of selenocysteine
Eur. J. Biochem.
264
74-84
1999
Bos taurus, Escherichia coli
Wang, P.F.; Marcinkeviciene, J.; Williams, C.H., Jr.; Blanchard, J.S.
Thioredoxin Reductase-Thioredoxin Fusion Enzyme from Mycobacterium leprae: Comparison with the Separately Expressed Thioredoxin Reductase
Biochemistry
37
16378-16389
1998
Escherichia coli, Mycobacterium leprae
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
Fernandes, A.P.; Fladvad, M.; Berndt, C.; Andresen, C.; Lillig, C.H.; Neubauer, P.; Sunnerhagen, M.; Holmgren, A.; Vlamis-Gardikas, A.
A novel monothiol glutaredoxin (GRX4) from Escherichia coli can serve as a substrate for thioredoxin reductase
J. Biol. Chem.
280
24544-24552
2005
Escherichia coli
Takahata, M.; Tamura, T.; Abe, K.; Mihara, H.; Kurokawa, S.; Yamamoto, Y.; Nakano, R.; Esaki, N.; Inagaki, K.
Selenite assimilation into formate dehydrogenase H depends on thioredoxin reductase in Escherichia coli
J. Biochem.
143
467-473
2008
Escherichia coli
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
Negri, A.; Rodriguez-Larrea, D.; Marco, E.; Jimenez-Ruiz, A.; Sanchez-Ruiz, J.; Gago, F.
Protein-protein interactions at an enzyme-substrate interface: Characterization of transient reaction intermediates throughout a full catalytic cycle of Escherichia coli thioredoxin reductase
Proteins Struct. Funct. Bioinform.
78
36-51
2010
Escherichia coli (P0A9P4), Escherichia coli
Lu, J.; Vlamis-Gardikas, A.; Kandasamy, K.; Zhao, R.; Gustafsson, T.; Engstrand, L.; Hoffner, S.; Engman, L.; Holmgren, A.
Inhibition of bacterial thioredoxin reductase An antibiotic mechanism targeting bacteria lacking glutathione
FASEB J.
27
1394-1403
2013
Escherichia coli, Haemonchus contortus
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