Information on EC 6.3.1.9 - trypanothione synthase

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
6.3.1.9
-
RECOMMENDED NAME
GeneOntology No.
trypanothione synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
glutathione + glutathionylspermidine + ATP = N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
show the reaction diagram
glutathione + spermidine + ATP = glutathionylspermidine + ADP + phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Acid amide formation
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
glutathionylspermidine biosynthesis
-
-
trypanothione biosynthesis
-
-
glutathione metabolism
-
-
Glutathione metabolism
-
-
Metabolic pathways
-
-
SYSTEMATIC NAME
IUBMB Comments
spermidine/glutathionylspermidine:glutathione ligase (ADP-forming)
The enzyme, characterized from several trypanosomatids (e.g. Trypanosoma cruzi) catalyses two subsequent reactions, leading to production of trypanothione from glutathione and spermidine. Some trypanosomatids (e.g. Crithidia species and some Leishmania species) also contain an enzyme that only carries out the first reaction (cf. EC 6.3.1.8, glutathionylspermidine synthase). The enzyme is bifunctional, and also catalyses the hydrolysis of glutathionylspermidine and trypanothione (cf. EC 3.5.1.78, glutathionylspermidine amidase).
CAS REGISTRY NUMBER
COMMENTARY hide
130246-69-4
-
213260-30-1
synthetase, trypanothione (Crithidia fasciculata strain HS6 gene Cf-TS) /GenBank AF006615-derived protein GI 3004644 /trypanothione synthetase (Crithidia fasciculata strain HS6 gene Cf-TS)
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
Leishmania donovani MHOM / IN / 80 / Dd8
-
Q8IFU8
UniProt
Manually annotated by BRENDA team
Leishmania donovani MHOM / IN / 83 / Ag
-
Q8IFU8
UniProt
Manually annotated by BRENDA team
Leishmania infantum JPCM5 /MHOM / MA / 67 / ITMAP263
-
UniProt
Manually annotated by BRENDA team
Leishmania infantum MHOM / MA / 67 / ITMAP263
-
UniProt
Manually annotated by BRENDA team
cell line 514-1313
Q8IEX1
UniProt
Manually annotated by BRENDA team
cell line 514-1313
Q8IEX1
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 glutathione + spermidine + 2 ATP
N1,N8-bis(glutathionyl)spermidine + 2 ADP + 2 phosphate
show the reaction diagram
gamma-L-Glu-L-alpha-aminobutyrylglycine + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP
?
show the reaction diagram
-
gamma-L-Glu-L-alpha-aminobutyrylglycine i.e. ophthalmic acid
-
-
-
gamma-L-Glu-L-Cys-Gly + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP
N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate
show the reaction diagram
gamma-L-Glu-L-Cys-Gly + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP + H2O
N1,N8-bis-(gamma-L-Glu-L-Cys-Gly)-spermidine + ADP + phosphate + NH3
show the reaction diagram
gamma-L-glutamyl-L-cysteinyl-glycine + N1-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ATP
N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate
show the reaction diagram
glutathione + glutathionylspermidine + ATP
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
show the reaction diagram
glutathione + N8-acetylspermidine + ATP
N1-glutathionyl-N8-acetylspermidine + ADP + phosphate
show the reaction diagram
-
-
-
?
glutathione + spermidine + 2 ATP
N1,N8-bis(glutathionyl)spermidine + 2 ADP + 2 phosphate
show the reaction diagram
glutathione + spermidine + ATP
glutathionylspermidine + ADP + phosphate
show the reaction diagram
glutathione + spermidine + ATP
N1-glutathionylspermidine + N8-glutathionylspermidine + ADP + phosphate
show the reaction diagram
N1-glutathionylspermidine + glutathione + ATP
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
show the reaction diagram
N8-glutathionylspermidine + glutathione + ATP
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
2 glutathione + spermidine + 2 ATP
N1,N8-bis(glutathionyl)spermidine + 2 ADP + 2 phosphate
show the reaction diagram
gamma-L-Glu-L-Cys-Gly + N1-(gamma-Glu-L-Cys-Gly)-spermidine + ATP
N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate
show the reaction diagram
gamma-L-glutamyl-L-cysteinyl-glycine + N1-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ATP
N1,N8-bis-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine + ADP + phosphate
show the reaction diagram
glutathione + glutathionylspermidine + ATP
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
show the reaction diagram
glutathione + spermidine + 2 ATP
N1,N8-bis(glutathionyl)spermidine + 2 ADP + 2 phosphate
show the reaction diagram
glutathione + spermidine + ATP
glutathionylspermidine + ADP + phosphate
show the reaction diagram
glutathione + spermidine + ATP
N1-glutathionylspermidine + N8-glutathionylspermidine + ADP + phosphate
show the reaction diagram
N1-glutathionylspermidine + glutathione + ATP
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
show the reaction diagram
N8-glutathionylspermidine + glutathione + ATP
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
(NH4)2SO4
optimal up to 50 mM
KCl
optimal up to 50 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,3,5-trimethyl-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]-1H-pyrazole-4-sulfonamide
-
-
1,4,7-trioxo-1lambda5,4lambda5,7lambda5-benzo[1,2-c:3,4-c':5,6-c'']tris[1,2,5]oxadiazole
-
64.4% activity remaining
1-(1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
-
83.5% activity remaining
1-(1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-5-(4-fluorophenyl)-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one
1-(3-(1-isobutyl-1H-pyrazol-4-yl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
-
-
1-(3-(1H-indol-4-yl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
-
-
1-(3-(3-chlorophenyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
-
-
1-(3-(3-fluorophenyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
-
-
1-(3-(3-pyridyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
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-
1-(3-(4-chlorophenyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
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-
1-(3-(furan-2-yl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
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-
1-(3-phenyl-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
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-
1-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)-3,3-dimethylbutan-2-one
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-
1-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)butan-2-one
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1-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)propan-2-one
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-
1-(5-(3,5-difluorophenyl)-2H-tetrazol-2-yl)-3,3-dimethylbutan-2-one
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-
1-(5-(3-fluorophenyl)-2H-tetrazol-2-yl)-3,3-dimethylbutan-2-one
-
-
1-(6-chloro-1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-hydroxy-3-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
1-(6-chloro-1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
1-(6-chloro-1,3-benzothiazol-2-yl)-4-(3,4-dimethoxybenzoyl)-5-(4-fluorophenyl)-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one
1-(tert-butylsulfonylmethyl)-3-(3-fluorophenyl)-1H-indazole
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-
1-[3-(3-fluorophenyl)-1H-indazol-1-yl]-3,3-dimethylbutan-2-one
-
i.e. DDD85811, inhibits growth of bloodstream Trypanosoma brucei in vitro
1-[5-(3-chloro-4-methylphenyl)-2H-tetrazol-2-yl]-3,3-dimethylbutan-2-one
-
-
1H-purine-2,6(3H,7H)-dione derivatives (Z)-8-(2-(2,4-dihydroxybenzylidene)hydrazinyl)-7-(2-hydroxy-3-phenoxy propyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione
-
88.5% activity remaining
-
2,4-dimethyl-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]-1,3-thiazole-5-sulfonamide
-
-
2,4-dimethyl-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]thiophene-3-sulfonamide
-
-
2,6-dichloro-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
-
-
2,6-dichloro-N-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]benzenesulfonamide
-
-
2,6-difluoro-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
-
-
2,6-dimethoxy-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]benzenesulfonamide
-
-
2-((tert-butylsulfonyl)methyl)-4-(2-fluorophenyl)thiazole
-
-
2-((tert-butylsulfonyl)methyl)-4-(2-methylphenyl)thiazole
-
-
2-((tert-butylsulfonyl)methyl)-4-(3-chlorophenyl)thiazole
-
-
2-((tert-butylsulfonyl)methyl)-4-(3-methoxyphenyl)thiazole
-
-
2-((tert-butylsulfonyl)methyl)-4-(phenyl)thiazole
-
-
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-1-(piperidin-1-yl)ethanone
-
-
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-N,N-dimethylacetamide
-
-
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-N-(2-(4-methylpiperazin-1-yl)ethyl)acetamide
-
-
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-N-(3-(4-methylpiperazin-1-yl)propyl)acetamide
-
-
2-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)-N,N-dimethylacetamide
-
-
2-(5-(3,5-difluorophenyl)-2H-tetrazol-2-yl)-1-phenylethanone
-
-
2-(9-bromo-3-chloro-6-oxo-7,12-dihydroindolo[3,2-d][1]benzazepin-5(6H)-yl)-N-[2-(methylamino)ethyl]acetamide
2-(tert-butylsulfonylmethyl)-4-(3-trifluoromethylphenyl)thiazole
-
-
2-methyl-N-((5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl)propane-2-sulfonamide
-
-
2-[3-(3-fluorophenyl)-1H-indazol-1-yl]-1-(piperidin-1-yl)ethanone
-
i.e. DDD86243, inhibits growth of bloodstream Trypanosoma brucei in vitro. Exposure to DDD86243 at 2 x EC50 for 72 h decreases intracellular trypanothione levels to less than 10% of wild type, with a corresponding 5fold increase in the precursor metabolite, glutathione
3,3-dimethyl-1-(3-(1-methyl-1H-indol-4-yl)-1H-indazol-1-yl)butan-2-one
-
-
3,3-dimethyl-1-(3-(naphthalen-2-yl)-1H-indazol-1-yl)butan-2-one
-
-
3,3-dimethyl-1-(3-(pyridin-4-yl)-1H-indazol-1-yl)butan-2-one
-
-
3,3-dimethyl-1-(3-(thiophen-3-yl)-1H-indazol-1-yl)butan-2-one
-
-
3,3-dimethyl-1-(5-phenyl-2H-tetrazol-2-yl)butan-2-one
-
-
3,3-dimethyl-1-[5-[3-(trifluoromethyl)phenyl]-2H-tetrazol-2-yl]butan-2-one
-
-
3,3-dimethyl-1-[5-[4-(trifluoromethyl)phenyl]-2H-tetrazol-2-yl]butan-2-one
-
-
3,5-dichloro-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
-
-
3-((3-(3-fluorophenyl)-1H-indazol-1-yl)methyl)-5-methylisoxazole
-
-
3-((3-(3-fluorophenyl)-1H-indazol-1-yl)methyl)-5-phenylisoxazole
-
-
3-(3-fluorophenyl)-1-(pyridin-2-ylmethyl)-1H-indazole
-
-
3-(3-fluorophenyl)-1-(pyridin-3-ylmethyl)-1H-indazole
-
-
3-(tert-butylsulfonylmethyl)-1-(3-fluorophenyl)-1H-indazole
-
-
3-(tert-butylsulfonylmethyl)-1-phenyl-1H-indazole
-
-
4-((3-(3-fluorophenyl)-1H-indazol-1-yl)methyl)-2,5-dimethyloxazole
-
-
4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-1-(6-methoxy-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-methoxyphenyl)-1-(6-methyl-1,3-benzothiazol-2-yl)-1,5-dihydro-2H-pyrrol-2-one
-
83.9% activity remaining
4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid
-
above 100 mM
4-acetyl-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
-
-
4-methoxy-N-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]benzenesulfonamide
-
-
4-methoxy-N-[[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]benzenesulfonamide
-
-
4-methyl-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
-
-
5-oxo-1H,3H-5lambda5-benzo[1,2-c:4,5-c']bis[1,2,5]oxadiazole
6-fluoro-3-oxo-4,5-didehydro-2,1,3lambda5-benzoxadiazole
-
84.1% activity remaining
ammonium sulfate
-
almost complete inhibition at 500 mM
betulin
competitive inhibition
buthionine sulfoximine
-
-
conessine
competitive allosteric inhibition
DL-(S,R)-buthionine sulfoximine
-
DL-(S,R)-BSO, a multitarget inhibitor of trypanothione synthesis, in vivo effects on nonthiol-supplied epimastigote cells, on Cys-supplied epimastigote cells, and on GSH-supplied epimastigote cells, overview. Inhibition of gamma-glutamylcysteine synthetase and trypanothione synthetase. Wild-type Trypanosoma brucei cells are not restored by supplementing with 0.08 mM GSH. The the L-(S,R)-BSO stereoisomer is more potent that the the D-(S,R)-BSO. Inhibitor docking analysis, binding structure
-
glutathione
GSH
Q8IEX1;
substrate inhibition
KCl
-
approx. 50% inhibition at 500 mM
Melarsen oxide
-
-
methyl (3-phenyl-1H-indazol-1-yl)acetate
-
-
N,N'-[6-(2,5-dichlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diyl]bis(N'-tert-butylurea)
N,N'-[6-(2H-1,3-benzodioxol-5-yl)pyrido[2,3-d]pyrimidine-2,7-diyl]bis(N'-tert-butylurea)
N,N-dibenzyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N,N-diethyl-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
-
-
N,N-diethyl-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamide
-
-
N-(1-phenylethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-(2-(dimethylamino)ethyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
-
-
N-(2-methoxyethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-(2-phenylethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-(3-(1H-imidazol-1-yl)propyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
-
-
N-(3-(dimethylamino)propyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
-
-
N-(4-chlorobenzyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
-
-
N-(4-chlorobenzyl)-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1Hindazol-1-yl)acetamide
-
-
N-(4-[methyl[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]sulfamoyl]phenyl)acetamide
-
-
N-(4-[[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]sulfamoyl]phenyl)acetamide
-
-
N-(butan-2-yl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-(thiophen-2-ylmethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-cyclohexyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-methyl-(3-(dimethylamino)propyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
-
-
N-phenyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-propyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
-
-
N-[(2-phenyl-1,3-thiazol-4-yl)methyl]naphthalene-2-sulfonamide
-
-
N-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]benzenesulfonamide
-
-
N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]naphthalene-1-sulfonamide
-
-
N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]thiophene-2-sulfonamide
-
-
N-[2-(methylamino)ethyl]-2-[6-oxo-9-(trifluoromethyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-5(6H)-yl]acetamide
N-[2-amino-6-(2H-1,3-benzodioxol-5-yl)pyrido[2,3-d]pyrimidin-7-yl]-N'-ethylthiourea
N-[2-amino-6-(naphthalen-2-yl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
N-[4-([[3-(2-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]sulfamoyl)phenyl]acetamide
-
-
N-[4-([[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]sulfamoyl)phenyl]acetamide
-
-
N-[[3-(2-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]benzenesulfonamide
-
-
N-[[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]benzenesulfonamide
-
-
N1,N10-bis[[4-(propan-2-yl)phenyl]methyl]decane-1,10-diamine
N1,N12-bis[(4-bromophenyl)methyl]dodecane-1,12-diamine
N1,N12-bis[(4-chlorophenyl)methyl]dodecane-1,12-diamine
N1,N3-bis[(4-methoxyphenyl)methyl]propane-1,3-diamine
-
-
N1,N4-bis[[4-(benzyloxy)-3-methoxyphenyl]methyl]butane-1,4-diamine
N1,N4-bis[[4-(benzyloxy)phenyl]methyl]butane-1,4-diamine
N1,N6-bis[[4-(benzyloxy)-3-methoxyphenyl]methyl]hexane-1,6-diamine
N1,N6-bis[[4-(benzyloxy)phenyl]methyl]hexane-1,6-diamine
N1,N8-bis[[4-(benzyloxy)-3-methoxyphenyl]methyl]octane-1,8-diamine
nifurtimox
-
-
Pentamidine
-
-
prochlorperazine
-
inhibitor DDD66604, binding mode and structure, overview
tert-butyl-4-(2-(2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamido)ethyl)piperazine-1-carboxylate
-
-
tomatine
competitive inhibition versus spermidine, uncompetitive inhibition with respect to ATP and GSH
triostam
-
-
trypanothione
-
competitive feedback inhibition
uvaol
competitive allosteric inhibition
[3-[4-([6-(3,4-dimethoxyphenyl)-7-[(ethylcarbamothioyl)amino]pyrido[2,3-d]pyrimidin-2-yl]amino)phenyl]propyl]molybdenum(1+)
Q8IEX1;
81.3% activity remaining
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,4,7-trioxo-1lambda5,4lambda5,7lambda5-benzo[1,2-c:3,4-c':5,6-c'']tris[1,2,5]oxadiazole
Q8IEX1;
activates, 118.8% activity
1-(1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
1-(1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-5-(4-fluorophenyl)-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one
Q8IEX1;
activates, 126.7% activity
1-(6-chloro-1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-hydroxy-3-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
Q8IEX1;
activates, 119.1% activity
1-(6-chloro-1,3-benzothiazol-2-yl)-4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
Q8IEX1;
activates, 119.0% activity
1-(6-chloro-1,3-benzothiazol-2-yl)-4-(3,4-dimethoxybenzoyl)-5-(4-fluorophenyl)-3-hydroxy-1,5-dihydro-2H-pyrrol-2-one
Q8IEX1;
activates, 123.2% activity
4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-1-(6-methoxy-1,3-benzothiazol-2-yl)-5-(4-methoxyphenyl)-1,5-dihydro-2H-pyrrol-2-one
Q8IEX1;
activates, 116.4% activity
4-(2,3-dihydro-1,4-benzodioxine-6-carbonyl)-3-hydroxy-5-(4-methoxyphenyl)-1-(6-methyl-1,3-benzothiazol-2-yl)-1,5-dihydro-2H-pyrrol-2-one
6-fluoro-3-oxo-4,5-didehydro-2,1,3lambda5-benzoxadiazole
-
activates, 118.8% activity
8-[(2E)-2-[(2,4-dihydroxyphenyl)methylidene]hydrazinyl]-7-(2-hydroxy-3-phenoxypropyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione
-
activates, 161.6% activity
J20
-
slightly stimulating
-
[3-[4-([6-(3,4-dimethoxyphenyl)-7-[(ethylcarbamothioyl)amino]pyrido[2,3-d]pyrimidin-2-yl]amino)phenyl]propyl]molybdenum(1+)
-
activates, 168.6% activity
additional information
Q8IEX1;
no effect by 1H-purine-2,6(3H,7H)-dione derivatives (Z)-8-(2-(2,4-dihydroxybenzylidene)hydrazinyl)-7-(2-hydroxy-3-phenoxy propyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione and 6-fluoro-3-oxo-4,5-didehydro-2,1,3lambda5-benzoxadiazole
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0066 - 0.053
ATP
0.914
gamma-L-Glu-L-Cys-Gly
-
-
0.032 - 0.407
glutathione
0.04 - 0.48
glutathionylspermidine
0.19
GSH
-
pH 8.0, with N1-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine
0.063 - 0.4
MgATP2-
0.066
N1-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine
-
pH 8.0
0.012 - 0.032
N1-glutathionylspermidine
0.007 - 0.032
N8-glutathionylspermidine
0.092 - 1.07
spermidine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.3 - 5.2
glutathione
8.7
glutathionylspermidine
pH 7.2, 25°C, recombinant trypanothione synthase
2.8
N1-(gamma-L-glutamyl-L-cysteinyl-glycyl)-spermidine
-
pH 8.0
10
N1-glutathionylspermidine
-
-
24.3
N8-glutathionylspermidine
-
-
28.6
spermidine
-
-
additional information
additional information
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0063
betulin
pH 8.0, 25°C, recombinant enzyme
0.0031
conessine
pH 8.0, 25°C, recombinant enzyme
0.132 - 1.085
glutathione
0.0068 - 0.0125
tomatine
0.223 - 0.377
trypanothione
0.0036
uvaol
pH 8.0, 25°C, recombinant enzyme
additional information
additional information
inhibition kinetics, overview
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0026
1,3,5-trimethyl-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]-1H-pyrazole-4-sulfonamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.1
1-(3-(1-isobutyl-1H-pyrazol-4-yl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0037
1-(3-(1H-indol-4-yl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.00035
1-(3-(3-chlorophenyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00009
1-(3-(3-fluorophenyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.003
1-(3-(3-pyridyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
1-(3-(4-chlorophenyl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0019
1-(3-(furan-2-yl)-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00015
1-(3-phenyl-1H-indazol-1-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.0003
1-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0027
1-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)butan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0065
1-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)propan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0019
1-(5-(3,5-difluorophenyl)-2H-tetrazol-2-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0015
1-(5-(3-fluorophenyl)-2H-tetrazol-2-yl)-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00012
1-(tert-butylsulfonylmethyl)-3-(3-fluorophenyl)-1H-indazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.000095
1-[3-(3-fluorophenyl)-1H-indazol-1-yl]-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH 8.0, 22°C
0.0072
1-[5-(3-chloro-4-methylphenyl)-2H-tetrazol-2-yl]-3,3-dimethylbutan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0022
2,4-dimethyl-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]-1,3-thiazole-5-sulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.024
2,4-dimethyl-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]thiophene-3-sulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0063
2,6-dichloro-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.016
2,6-dichloro-N-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0061
2,6-difluoro-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
2,6-dimethoxy-N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0011
2-((tert-butylsulfonyl)methyl)-4-(2-fluorophenyl)thiazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0032
2-((tert-butylsulfonyl)methyl)-4-(2-methylphenyl)thiazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0004
2-((tert-butylsulfonyl)methyl)-4-(3-chlorophenyl)thiazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.012
2-((tert-butylsulfonyl)methyl)-4-(3-methoxyphenyl)thiazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0012
2-((tert-butylsulfonyl)methyl)-4-(phenyl)thiazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00014
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-1-(piperidin-1-yl)ethanone
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00011
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-N,N-dimethylacetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00086
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-N-(2-(4-methylpiperazin-1-yl)ethyl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00083
2-(3-(3-fluorophenyl)-1H-indazol-1-yl)-N-(3-(4-methylpiperazin-1-yl)propyl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0006
2-(5-(3,5-dichlorophenyl)-2H-tetrazol-2-yl)-N,N-dimethylacetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.045
2-(5-(3,5-difluorophenyl)-2H-tetrazol-2-yl)-1-phenylethanone
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00015
2-(9-bromo-3-chloro-6-oxo-7,12-dihydroindolo[3,2-d][1]benzazepin-5(6H)-yl)-N-[2-(methylamino)ethyl]acetamide
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0011
2-(tert-butylsulfonylmethyl)-4-(3-trifluoromethylphenyl)thiazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.037
2-methyl-N-((5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl)propane-2-sulfonamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.00014
2-[3-(3-fluorophenyl)-1H-indazol-1-yl]-1-(piperidin-1-yl)ethanone
Trypanosoma brucei;
-
pH 8.0, 22°C
0.1
3,3-dimethyl-1-(3-(1-methyl-1H-indol-4-yl)-1H-indazol-1-yl)butan-2-one
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.1
3,3-dimethyl-1-(3-(naphthalen-2-yl)-1H-indazol-1-yl)butan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0003
3,3-dimethyl-1-(3-(pyridin-4-yl)-1H-indazol-1-yl)butan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0004
3,3-dimethyl-1-(3-(thiophen-3-yl)-1H-indazol-1-yl)butan-2-one
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.0088
3,3-dimethyl-1-(5-phenyl-2H-tetrazol-2-yl)butan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0035
3,3-dimethyl-1-[5-[3-(trifluoromethyl)phenyl]-2H-tetrazol-2-yl]butan-2-one
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
3,3-dimethyl-1-[5-[4-(trifluoromethyl)phenyl]-2H-tetrazol-2-yl]butan-2-one
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.0058
3,5-dichloro-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
3-((3-(3-fluorophenyl)-1H-indazol-1-yl)methyl)-5-methylisoxazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
3-((3-(3-fluorophenyl)-1H-indazol-1-yl)methyl)-5-phenylisoxazole
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.0029
3-(3-fluorophenyl)-1-(pyridin-2-ylmethyl)-1H-indazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0045
3-(3-fluorophenyl)-1-(pyridin-3-ylmethyl)-1H-indazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00008
3-(tert-butylsulfonylmethyl)-1-(3-fluorophenyl)-1H-indazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00022
3-(tert-butylsulfonylmethyl)-1-phenyl-1H-indazole
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.028
4-((3-(3-fluorophenyl)-1H-indazol-1-yl)methyl)-2,5-dimethyloxazole
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.0087
4-acetyl-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.011
4-methoxy-N-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.004
4-methoxy-N-[[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
4-methyl-N-[(2-phenyl-1,3-thiazol-4-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0313
5-oxo-1H,3H-5lambda5-benzo[1,2-c:4,5-c']bis[1,2,5]oxadiazole
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0117
betulin
Leishmania donovani;
G5D5D5
pH 8.0, 25°C, recombinant enzyme
0.0134
conessine
Leishmania donovani;
G5D5D5
pH 8.0, 25°C, recombinant enzyme
0.02
methyl (3-phenyl-1H-indazol-1-yl)acetate
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0138
N,N'-[6-(2,5-dichlorophenyl)pyrido[2,3-d]pyrimidine-2,7-diyl]bis(N'-tert-butylurea)
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0153
N,N'-[6-(2H-1,3-benzodioxol-5-yl)pyrido[2,3-d]pyrimidine-2,7-diyl]bis(N'-tert-butylurea)
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.1
N,N-dibenzyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0002
N,N-diethyl-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.015
N,N-diethyl-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0056
N-(1-phenylethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.000145
N-(2-(dimethylamino)ethyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.03
N-(2-methoxyethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.005
N-(2-phenylethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00035
N-(3-(1H-imidazol-1-yl)propyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.000045
N-(3-(dimethylamino)propyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
N-(4-chlorobenzyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.003
N-(4-chlorobenzyl)-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1Hindazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.05
N-(4-[methyl[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]sulfamoyl]phenyl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0059
N-(4-[[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]sulfamoyl]phenyl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.012
N-(butan-2-yl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0039
N-(thiophen-2-ylmethyl)-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
N-cyclohexyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.00017
N-methyl-(3-(dimethylamino)propyl)-2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
N-phenyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.013
N-propyl-2-[3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.002 - 4
N-[(2-phenyl-1,3-thiazol-4-yl)methyl]naphthalene-2-sulfonamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.05
N-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.1
N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]naphthalene-1-sulfonamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.0085
N-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl)methyl]thiophene-2-sulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.00035
N-[2-(methylamino)ethyl]-2-[6-oxo-9-(trifluoromethyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-5(6H)-yl]acetamide
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0136
N-[2-amino-6-(2H-1,3-benzodioxol-5-yl)pyrido[2,3-d]pyrimidin-7-yl]-N'-ethylthiourea
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0321
N-[2-amino-6-(naphthalen-2-yl)pyrido[2,3-d]pyrimidin-7-yl]-N'-tert-butylurea
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0037
N-[4-([[3-(2-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]sulfamoyl)phenyl]acetamide
Trypanosoma brucei;
-
above, pH and temperature not specified in the publication
0.0017
N-[4-([[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]sulfamoyl)phenyl]acetamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.025
N-[[3-(2-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.015
N-[[3-(2-methylphenyl)-1,2,4-oxadiazol-5-yl]methyl]benzenesulfonamide
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.0478
N1,N10-bis[[4-(propan-2-yl)phenyl]methyl]decane-1,10-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0259
N1,N12-bis[(4-bromophenyl)methyl]dodecane-1,12-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0515
N1,N12-bis[(4-chlorophenyl)methyl]dodecane-1,12-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0234
N1,N4-bis[[4-(benzyloxy)-3-methoxyphenyl]methyl]butane-1,4-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0567
N1,N4-bis[[4-(benzyloxy)phenyl]methyl]butane-1,4-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0263
N1,N6-bis[[4-(benzyloxy)-3-methoxyphenyl]methyl]hexane-1,6-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0391
N1,N6-bis[[4-(benzyloxy)phenyl]methyl]hexane-1,6-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0496
N1,N8-bis[[4-(benzyloxy)-3-methoxyphenyl]methyl]octane-1,8-diamine
Leishmania infantum;
-
pH 7.4, 22°C, recombinant enzyme
0.0029
tert-butyl-4-(2-(2-(3-(3-fluorophenyl)-1H-indazol-1-yl)acetamido)ethyl)piperazine-1-carboxylate
Trypanosoma brucei;
-
pH and temperature not specified in the publication
0.018
tomatine
Leishmania donovani;
G5D5D5
pH 8.0, 25°C, recombinant enzyme
0.0112
uvaol
Leishmania donovani;
G5D5D5
pH 8.0, 25°C, recombinant enzyme
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.1 - 2.2
purified recombinant trypanothione synthase performing the trypanothione synthase reaction, average of the activity of recombinant enzymes expressed from different constructs, overview
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
reaction step 2, no activity at pH 8.0
7 - 8
-
reaction step 1
7.2 - 7.5
assay at
7.5 - 7.8
-
synthesis of both mono-glutathionylspermidine and di-glutathionylspermidine conjugates
8 - 8.5
Q8IFU8;
-
8.5
with substrates glutathionylspermidine and spermidine
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5 - 11
inactive above or below
5.5 - 10
-
approx. 50% of maximal activity at pH 6.6 and pH 9.5 respectively
6 - 10
Q8IFU8;
activity range, profile overview
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25 - 37
-
assay at
30
Q8IFU8;
assay at
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
10 - 60
residual activity above
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
Leishmania major;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
64000
-
gel filtration
73560
-
deduced from nucleotide sequence
73740
-
MALDI mass spectrometry
73744
-
1 * 73744, MALDI mass spectrometry
81000
-
gel filtration
82000
-
x * 82000, SDS-PAGE
87000
-
1 * 87000, SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
determination of three crystal forms, 18°C, hanging drop vapor diffusion method, 0.001 ml of protein solution is mixed with 0.001 ml of reservoir solution, for crystal form I were optimized to a reservoir of 1.4 M (NH4)2SO4, 100 mM HEPES, pH 7.0, 200 mM NaBr, crystal form II to 1.6 M (NH4)2SO4, 100 mM HEPES, pH 7.0, and 200 mM NaBr, and crystal form III to 14% polyethylene glycol 8000, 15% glycerol and 100 mM KCl, within 2 days, X-ray diffraction structure determination and analysis at 2.3-3.6 A resolution, modelling; hanging gamma-drop vapor diffusion method, structure of Leishmania major trypanothione synthetase-amidase, determined in three crystal forms, reveals two catalytic domains
-
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the C-terminal segment of the protein contributes to the amidase domain structure, and its loss likely destabilizes the fold
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ammonium sulfate, DEAE-cellulose, partially purified
recombinant enzyme from Escherichia coli strain BL21(DE3)
-
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography, dialysis, and ion exchange chromatography
recombinant His-tagged enzyme from Escherichia coli strain BL21 star (DE3) by nickel affinity chromatography and tag cleavage through thrombin
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration, followed by tag cleavage though thrombin, the tag is removed by benzamidine affinity chromatography, the purified enzyme is dialysed
Q8IFU8;
recombinant His-tagged enzyme from Escherichia coli strain Tuner(DE3) by nickel affinity chromatography and tag cleavage by tobacco etch virus protease, followed by a second nickel affinity chromatography
-
recombinant His-tagged enzyme from Escherichia coli strains BL21(DE3) or Tuner (DE3) by affinity chromatography
recombinant His-tagged TcTryS, Ni2+-affinity, anion exchange
-
recombinant His-tagged wild-type enzyme and mutants from Escherichia coli by nickel affinity chromatography
recombinant His6-tagged enzyme from Escherichia coli strain Tuner (DE3) CodonPlus by nickel affinity chromatography and gel filtration
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
DNA sequence determination and analysis, expression of wild-type enzyme and mutants in Escherichia coli as His-tagged or Nus-fusion proteins
DNA sequence determination, cloning and RNAi transfection, expression in Escherichia coli
-
enzyme expression analysis, cloning and transfection of RNAi
-
expressed in Escherichia coli
-
expression in Escherichia coli
-
expression in Escherichia coli and Saccharomyces cerevisiae
expression of His-tagged enzyme in Escherichia coli strain BL21 star (DE3)
gene TRS, recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strains BL21(DE3) or Tuner (DE3)
-
gene TRYS, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression of His-tagged enzyme in Escherichia coli
gene tryS, DNA and amino acid sequence determination and analysis, sequence comparisons, real-time PCR expression analysis, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
Q8IFU8;
gene tryS, recombinant expression in Escherichia coli strain BL21(DE3)
-
gene tryS, recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strains BL21(DE3) or Tuner (DE3)
recombinant expression of His-tagged enzyme in Escherichia coli strain Tuner(DE3)
-
recombinant expression of His6-tagged enzyme in Escherichia coli strain Tuner (DE3) CodonPlus
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
H2O2 treatment up to 0.150 mM for 8 hrs leads to 2fold increased expression of LdTryS probably to cope up with oxidative stress generated by H2O2. Stage-dependent up-regulation of trypanothione synthetase in amphotericin B resistant Leishmania donovani
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C59A
-
mutant lacks the amidase activity, while the synthetase activity is similar to wild-type. Constructed for the production of trypanothione and trypanothione disulfide in >200 mg quantities. The protocol also allows the synthesis of related glutathione conjugates
R553E
site-directed mutagenesis
R553K
site-directed mutagenesis
R553L
site-directed mutagenesis
R553Q
site-directed mutagenesis
R613E
site-directed mutagenesis
R613K
site-directed mutagenesis
R613L
site-directed mutagenesis
R613Q
site-directed mutagenesis
DELTAN236
-
unable to produce trypanothione
DELTAN250
-
unable to produce trypanothione
C57A
-
functional synthetase devoid of amidase activity. In the presence of inducer, this line showed decreased growth in vitro and decreased virulence in vivo, indicating that the amidase function is not absolutely required for viability
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
drug development
pharmacology
-
the enzyme would serve as a potential target for antiparasitic chemotherapy
synthesis
-
production of trypanothione and trypanothione disulfide in >200 mg quantities by mutant C59A lacking the amidase activity. The protocol also allows the synthesis of related glutathione conjugates
additional information