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Information on EC 1.8.1.12 - trypanothione-disulfide reductase and Organism(s) Trypanosoma brucei brucei and UniProt Accession P39051

for references in articles please use BRENDA:EC1.8.1.12
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IUBMB Comments
Trypanothione disulfide is the oxidized form of N1,N8-bis(glutathionyl)-spermidine from the insect-parasitic trypanosomatid Crithidia fasciculata. The enzyme from Crithidia fasciculata is a flavoprotein (FAD), whose activity is dependent on a redox-active cystine at the active centre. (cf. EC 1.8.1.7, glutathione-disulfide reductase)
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Trypanosoma brucei brucei
UNIPROT: P39051
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The taxonomic range for the selected organisms is: Trypanosoma brucei brucei
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
trypanothione reductase, li-tryr, ldtryr, trypanothione disulfide reductase, lbtryr, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
N(1),N(8)-bis(glutathionyl)spermidine reductase
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-
-
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NADPH2:trypanothione oxidoreductase
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-
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trypanothione disulfide reductase
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-
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trypanothione reductase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
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-
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oxidation
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reduction
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-
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PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
trypanothione:NADP+ oxidoreductase
Trypanothione disulfide is the oxidized form of N1,N8-bis(glutathionyl)-spermidine from the insect-parasitic trypanosomatid Crithidia fasciculata. The enzyme from Crithidia fasciculata is a flavoprotein (FAD), whose activity is dependent on a redox-active cystine at the active centre. (cf. EC 1.8.1.7, glutathione-disulfide reductase)
CAS REGISTRY NUMBER
COMMENTARY hide
102210-35-5
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
trypanothione disulfide + NADPH + H+
trypanothione + NADP+
show the reaction diagram
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-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
trypanothione disulfide + NADPH + H+
trypanothione + NADP+
show the reaction diagram
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-ethyl-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 14% inhibition
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1-[1-(4,5-diphenylthiophen-2-yl)cyclohexyl]pyrrolidine
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 11% inhibition
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1-[1-[4,5-bis(2H-1,3-benzodioxol-5-yl)thiophen-2-yl]cyclohexyl]pyrrolidine
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 11% inhibition
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1-[2-(4-methylpiperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase,60 % inhibition
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1-[2-(morpholin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 34% inhibition
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1-[2-(piperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 80% inhibition
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1-[2-(piperidin-4-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 68% inhibition
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3,3'-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophene-2,3-diyl]dipyridine
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 10% inhibition
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4-[(7-chloro-4-nitro-2,1,3-benzothiadiazol-5-yl)sulfanyl]quinazoline
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reversible. Compound inhibits parasite proliferation with EC50 values between 50 and 5 microM
5,7-dichloro-4-nitro-2,1,3-benzothiadiazole
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reversible. Compound inhibits parasite proliferation with EC50 values between 50 and 5 microM
5-[2-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 14% inhibition
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5-[2-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 29% inhibition
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5-[3-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 23% inhibition
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5-[3-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 14% inhibition
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5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
0.012 mM inhibitor in presence of 0.04 mM trypanothione reductase, 19% inhibition
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[[(7-nitro-2,1,3-benzoxadiazol-4-yl)methyl]sulfanyl]methyl phenylcarbamate
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reversible. Compound inhibits parasite proliferation with EC50 values between 50 and 5 microM
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0065
1-[2-(4-methylpiperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
Trypanosoma brucei brucei
pH and temperature not specified in the publication
-
0.0038
1-[2-(piperazin-1-yl)ethyl]-5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]-1,3-thiazol-2-yl]-1H-indole
Trypanosoma brucei brucei
pH and temperature not specified in the publication
-
0.00058
4-[(7-chloro-4-nitro-2,1,3-benzothiadiazol-5-yl)sulfanyl]quinazoline
Trypanosoma brucei brucei
-
pH 7.5, 22°C
0.00061
5,7-dichloro-4-nitro-2,1,3-benzothiadiazole
Trypanosoma brucei brucei
-
pH 7.5, 22°C
0.035
5-[2-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
Trypanosoma brucei brucei
pH and temperature not specified in the publication
-
0.01
5-[2-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-3-yl]-1H-indole
Trypanosoma brucei brucei
pH and temperature not specified in the publication
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0.02
5-[3-(1-benzothiophen-5-yl)-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
Trypanosoma brucei brucei
pH and temperature not specified in the publication
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0.025
5-[3-phenyl-5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
Trypanosoma brucei brucei
pH and temperature not specified in the publication
-
0.012
5-[5-[1-(pyrrolidin-1-yl)cyclohexyl]thiophen-2-yl]-1H-indole
Trypanosoma brucei brucei
pH and temperature not specified in the publication
-
0.00027
[[(7-nitro-2,1,3-benzoxadiazol-4-yl)methyl]sulfanyl]methyl phenylcarbamate
Trypanosoma brucei brucei
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pH 7.5, 22°C
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug target
the enzyme is a promising targets for the development of drugs selective against parasites of the family of trypanosomatids
physiological function
trypanosomatids possess a unique redox metabolism based on the dithiol trypanothione and the enzyme trypanothione reductase (TR) that differs distinctively from the glutathione and glutathione reductase-based metabolism in mammals
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TYTR_TRYBB
492
0
53284
Swiss-Prot
other Location (Reliability: 4)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method
quantitative structure–activity relationship models to predict the activity of inhibitors and investigation on structural requirements for the selective inhibition
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Ferreira, L.G.; Andricopulo, A.D.
Inhibitors of Trypanosoma brucei trypanothione reductase comparative molecular field analysis modeling and structural basis for selective inhibition
Future Med. Chem.
5
1753-1762
2013
Trypanosoma brucei brucei (Q389T8), Trypanosoma brucei brucei 927/4 GUTat10.1 (Q389T8)
Manually annotated by BRENDA team
Beig, M.; Oellien, F.; Garoff, L.; Noack, S.; Krauth-Siegel, R.L.; Selzer, P.M.
Trypanothione reductase a target protein for a combined in vitro and in silico screening approach
PLoS Negl. Trop. Dis.
9
e0003773
2015
Trypanosoma brucei brucei
Manually annotated by BRENDA team
De Gasparo, R.; Brodbeck-Persch, E.; Bryson, S.; Hentzen, N.B.; Kaiser, M.; Pai, E.F.; Krauth-Siegel, R.L.; Diederich, F.
Biological evaluation and X-ray co-crystal structures of cyclohexylpyrrolidine ligands for trypanothione reductase, an enzyme from the redox metabolism of Trypanosoma
ChemMedChem
13
957-967
2018
Trypanosoma cruzi, Trypanosoma brucei brucei (Q389T8), Trypanosoma brucei brucei 927/4 GUTat10.1 (Q389T8)
Manually annotated by BRENDA team