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Literature summary for 6.3.1.9 extracted from
- Genetic and chemical analyses reveal that trypanothione synthetase but not glutathionylspermidine synthetase is essential for Leishmania infantum (2014), Free Radic. Biol. Med., 73, 229-238 .
Application
| Application | Comment | Organism |
|---|---|---|
| additional information | enzyme TRYS is a valuable target for antiparasitic drug development | Leishmania infantum |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of His6-tagged enzyme in Escherichia coli strain Tuner (DE3) CodonPlus | Leishmania infantum |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | elimination of both LiTRYS alleles is not possible unless parasites are previously complemented with an episomal copy of the gene. Retention of extrachromosomal LiTRYS in the trys-/-/+TRYS line after several passages in culture | Leishmania infantum |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| N-[2-(methylamino)ethyl]-2-[6-oxo-9-(trifluoromethyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-5(6H)-yl]acetamide | i.e. FS-554, N5-substituted paullone | Leishmania infantum |  |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Mg2+ | required | Leishmania infantum | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| glutathione + glutathionylspermidine + ATP | Leishmania infantum | - |
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate | - |
? | |
| glutathione + glutathionylspermidine + ATP | Leishmania infantum MHOM / MA / 67 / ITMAP263 | - |
N1,N8-bis(glutathionyl)spermidine + ADP + phosphate | - |
? | |
| glutathione + spermidine + ATP | Leishmania infantum | - |
glutathionylspermidine + ADP + phosphate | - |
? | |
| glutathione + spermidine + ATP | Leishmania infantum MHOM / MA / 67 / ITMAP263 | - |
glutathionylspermidine + ADP + phosphate | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Leishmania infantum | A4I2Z3 | - |
- |
| Leishmania infantum MHOM / MA / 67 / ITMAP263 | A4I2Z3 | - |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-tagged enzyme from Escherichia coli strain Tuner (DE3) CodonPlus by nickel affinity chromatography and gel filtration | Leishmania infantum |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| amastigote | LiTRYS is constitutively expressed in Leishmania infantum axenic amastigotes | Leishmania infantum | - |
| additional information | in both life cycle stages of the parasite, the extracellular promastigotes residing in the insect vector and the intracellular amastigotes thriving in mammalian hosts. Expression of LiTRYS is detected throughout the Leishmania infantum life cycle | Leishmania infantum | - |
| promastigote | LiTRYS is constitutively expressed along Leishmania infantum promastigote growth | Leishmania infantum | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| glutathione + glutathionylspermidine + ATP | - |
Leishmania infantum | N1,N8-bis(glutathionyl)spermidine + ADP + phosphate | - |
? | |
| glutathione + glutathionylspermidine + ATP | - |
Leishmania infantum MHOM / MA / 67 / ITMAP263 | N1,N8-bis(glutathionyl)spermidine + ADP + phosphate | - |
? | |
| glutathione + spermidine + ATP | - |
Leishmania infantum | glutathionylspermidine + ADP + phosphate | - |
? | |
| glutathione + spermidine + ATP | - |
Leishmania infantum MHOM / MA / 67 / ITMAP263 | glutathionylspermidine + ADP + phosphate | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 79000, recombinant enzyme, SDS-PAGE | Leishmania infantum |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| LiTRYS | - |
Leishmania infantum |
| trypanothione synthase | - |
Leishmania infantum |
| TryS | - |
Leishmania infantum |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 22 | - |
assay at room temperature | Leishmania infantum |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 7.4 | - |
assay at | Leishmania infantum |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Leishmania infantum | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | genetic knockout mutants of both alleles are not viable, chemical targeting of LiTRYS with a drug-like compound FS-554 also leads to parasite death | Leishmania infantum |
| physiological function | trypanothione synthetase, EC 6.3.1.9, but not glutathionylspermidine synthetase, EC 6.3.1.8, is essential for Leishmania infantum | Leishmania infantum |
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