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Literature summary extracted from

  • 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 (2011), Biochemistry, 50, 5870-5882.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.8.1.B1 medicine the enzyme is a drug target for schistosomiasis Schistosoma mansoni

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.8.1.B1 expressed in Escherichia coli BL21(DE3) cells Schistosoma mansoni

Protein Variants

EC Number Protein Variants Comment Organism
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.8.1.B1 auranofin
-
 Schistosoma mansoni
1.8.1.B1 furoxan
-
 Schistosoma mansoni
1.8.1.B1 potassium antimony tartrate
-
 Schistosoma mansoni

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.8.1.B1 0.007
-
 thioredoxin disulfide mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.007
-
 thioredoxin disulfide mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.008
-
 thioredoxin disulfide mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.008
-
 thioredoxin disulfide mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.008
-
 thioredoxin disulfide wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.013
-
 GSSG mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 0.015
-
 thioredoxin disulfide mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.016
-
 GSSG mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 0.022
-
 thioredoxin disulfide mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.023
-
 GSSG mutant enzyme C28A/C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.024
-
 GSSG mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.031
-
 GSSG mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.036
-
 GSSG mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.042
-
 GSSG wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 0.071
-
 GSSG mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 0.189
-
 GSSG mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.8.1.B1 GSSG + NADPH + H+ Schistosoma mansoni
-
 GSH + NADP+
-
 ?
1.8.1.B1 thioredoxin disulfide + NADPH + H+ Schistosoma mansoni
-
 thioredoxin + NADP+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.8.1.B1 Schistosoma mansoni
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.8.1.B1 2',5'-ADP Sepharose column chromatography and Sephadex G-25 gel filtration Schistosoma mansoni

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.8.1.B1 5,5'-dithiobis(2-nitrobenzoic acid) + NADPH + H+
-
 Schistosoma mansoni 2-nitro-5-thiobenzoate + NADP+
-
 ?
1.8.1.B1 GSSG + NADPH + H+
-
 Schistosoma mansoni GSH + NADP+
-
 ?
1.8.1.B1 thioredoxin disulfide + NADPH + H+
-
 Schistosoma mansoni thioredoxin + NADP+
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.8.1.B1 TGR
-
 Schistosoma mansoni

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.8.1.B1 0.6
-
 GSSG mutant enzyme C28A/C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 0.7
-
 GSSG mutant enzyme C28A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 3.5
-
 GSSG mutant enzyme C31A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 3.5
-
 thioredoxin disulfide mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 4
-
 GSSG mutant enzyme U597C, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 5
-
 GSSG mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 5
-
 GSSG mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 7
-
 GSSG mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 8
-
 thioredoxin disulfide mutant enzyme C520A/C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 8
-
 thioredoxin disulfide mutant enzyme C574A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 9
-
 thioredoxin disulfide mutant enzyme C520A, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 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 Schistosoma mansoni
1.8.1.B1 19.4
-
 GSSG wild type enzyme, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni
1.8.1.B1 25
-
 GSSG mutant enzyme C31S, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni

Cofactor

EC Number Cofactor Comment Organism Structure
1.8.1.B1 FAD
-
 Schistosoma mansoni
1.8.1.B1 NADPH
-
 Schistosoma mansoni

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.8.1.B1 0.0000032
-
 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 Schistosoma mansoni auranofin
1.8.1.B1 0.0000054
-
 wild type enzyme, with GSSG as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni auranofin
1.8.1.B1 0.000008
-
 wild type enzyme, with GSSG as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni potassium antimony tartrate
1.8.1.B1 0.0000083
-
 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 Schistosoma mansoni auranofin
1.8.1.B1 0.000009
-
 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 Schistosoma mansoni potassium antimony tartrate
1.8.1.B1 0.000045
-
 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 Schistosoma mansoni potassium antimony tartrate
1.8.1.B1 0.003
-
 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 Schistosoma mansoni furoxan
1.8.1.B1 0.0032
-
 wild type enzyme, with GSSG as substrate, in 0.1 M potassium phosphate buffer and 10 mM EDTA (pH 7.4) at 25°C Schistosoma mansoni furoxan
1.8.1.B1 0.0054
-
 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 Schistosoma mansoni furoxan

General Information

EC Number General Information Comment Organism
1.8.1.B1 physiological function the enzyme plays a crucial role in maintaining redox homeostasis Schistosoma mansoni