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Literature summary for 1.8.1.9 extracted from

  • Rackham, O.; Shearwood, A.M.; Thyer, R.; McNamara, E.; Davies, S.M.; Callus, B.A.; Miranda-Vizuete, A.; Berners-Price, S.J.; Cheng, Q.; Arner, E.S.; Filipovska, A.
    Substrate and inhibitor specificities differ between human cytosolic and mitochondrial thioredoxin reductases: Implications for development of specific inhibitors (2011), Free Radic. Biol. Med., 50, 689-699.
    View publication on PubMed
Search for more literature for 1.8.1.9

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli BL21(DE3) or ER2566 cells Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
auranofin efficient inhibition, about 20% residual activity after 8 h at 0.005 mM, about 7% residual activity after 8 h at 0.05 mM Homo sapiens
aurothioglucose about 90% residual activity after 8 h at 0.005 mM, about 80% residual activity after 8 h at 0.05 mM Homo sapiens
cisplatin about 40% residual activity after 8 h at 0.005 mM or 0.05 mM Homo sapiens
[(iPr2Im)2Au]Cl mainly inhibits isoform TrxR2, about 30% residual activity after 8 h at 0.005 mM or 0.05 mM Homo sapiens
[Au(d2pype)2]Cl mainly inhibits isoform TrxR1, about 30% residual activity after 8 h at 0.005 mM, about 10% residual activity after 8 h at 0.05 mM Homo sapiens
[Au(d2pypp)2]Cl about 30% residual activity after 8 h at 0.005 mM, about 10% residual activity after 8 h at 0.05 mM Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0019
-
 Lipoamide isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
0.0027
-
 lipoic acid isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
0.0043
-
 Lipoamide isoform TrxR2, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
0.105
-
 5,5'-dithiobis(2-nitrobenzoic acid) isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 7.0, at 37°C Homo sapiens
0.39
-
 5,5'-dithiobis(2-nitrobenzoic acid) isoform TrxR2, in 50 mM Tris-HCl, 1 mM EDTA, pH 7.0, at 37°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cytosol isoform TrxR1 Homo sapiens 5829
-
mitochondrion isoform TrxR2 Homo sapiens 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
additional information selenoprotein Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
53117
-
 2 * 53117, isoform TrxR1, calculated from amino acid sequence Homo sapiens
54769
-
 2 * 54769, isoform TrxR2, calculated from amino acid sequence Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
thioredoxin 1 + NADP+ Homo sapiens TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2 thioredoxin 1 disulfide + NADPH + H+
-
 ?
thioredoxin 2 + NADP+ Homo sapiens TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2 thioredoxin 2 disulfide + NADPH + H+
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
2',5'-ADP Sepharose column chromatography, PAO Sepharose column chromatography, and Superdex 200 gel filtration Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+ isoform TrxR2 displays strikingly lower activity with 5,5'-dithiobis(2-nitrobenzoic acid) compared to isoform TrxR1 Homo sapiens 5'-thionitrobenzoic acid + NADP+
-
 ?
juglone + NADPH + H+ isoform TrxR2 displays strikingly lower activity with juglone compared to isoform TrxR1 Homo sapiens ?
-
 ?
lipoamide + NADPH + H+ isoform TrxR2 displays strikingly lower activity with lipoamide compared to isoform TrxR1 Homo sapiens ?
-
 ?
lipoic acid + NADPH + H+ substrate for isoform TrxR1 Homo sapiens ?
-
 ?
additional information isoform TrxR2 cannot reduce lipoic acid Homo sapiens ?
-
 ?
thioredoxin 1 + NADP+ TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2 Homo sapiens thioredoxin 1 disulfide + NADPH + H+
-
 ?
thioredoxin 2 + NADP+ TrxR2 prefers its endogenous substrate thioredocin 2 over thioredoxin 1 (10fold), whereas isoform TrxR1 efficiently reduces both thioredoxin 1 and thioredoxin 2 Homo sapiens thioredoxin 2 disulfide + NADPH + H+
-
 ?

Subunits

Subunits Comment Organism
homodimer 2 * 53117, isoform TrxR1, calculated from amino acid sequence Homo sapiens
homodimer 2 * 54769, isoform TrxR2, calculated from amino acid sequence Homo sapiens

Synonyms

Synonyms Comment Organism
TrxR1
-
 Homo sapiens
TrxR2
-
 Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.6
-
 Lipoamide isoform TrxR2, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
1.8
-
 lipoic acid isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
3.3
-
 Lipoamide isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
8.28
-
 5,5'-dithiobis(2-nitrobenzoic acid) isoform TrxR2, in 50 mM Tris-HCl, 1 mM EDTA, pH 7.0, at 37°C Homo sapiens
18.73
-
 5,5'-dithiobis(2-nitrobenzoic acid) isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 7.0, at 37°C Homo sapiens

Cofactor

Cofactor Comment Organism Structure
FAD
-
 Homo sapiens
NADPH dependent on Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
21.2
-
 5,5'-dithiobis(2-nitrobenzoic acid) isoform TrxR2, in 50 mM Tris-HCl, 1 mM EDTA, pH 7.0, at 37°C Homo sapiens
178
-
 5,5'-dithiobis(2-nitrobenzoic acid) isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 7.0, at 37°C Homo sapiens
372
-
 Lipoamide isoform TrxR2, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
667
-
 lipoic acid isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens
1737
-
 Lipoamide isoform TrxR1, in 50 mM Tris-HCl, 1 mM EDTA, pH 8.0, at 37°C Homo sapiens