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Literature summary extracted from

  • Sousa, A.F.; Gomes-Alves, A.G.; Benitez, D.; Comini, M.A.; Flohe, L.; Jaeger, T.; Passos, J.; Stuhlmann, F.; Tomas, A.M.; Castro, H.
    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 .
    View publication on PubMed

Application

EC Number Application Comment Organism
6.3.1.8 additional information GSPS is no valuable target for antiparasitic drug development Leishmania infantum
6.3.1.9 additional information enzyme TRYS is a valuable target for antiparasitic drug development Leishmania infantum

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.3.1.8 recombinant expression of His6-tagged enzyme in Escherichia coli strain Rosetta (DE3) in inclusion bodies Leishmania infantum
6.3.1.9 recombinant expression of His6-tagged enzyme in Escherichia coli strain Tuner (DE3) CodonPlus Leishmania infantum

Protein Variants

EC Number Protein Variants Comment Organism
6.3.1.8 additional information generation of a knockout GSPS mutant line by gene targeting, the mutant is viable and capable of replicating in both life cycle stages of the parasite, the extracellular promastigotes residing in the insect vector and the intracellular amastigotes thriving in mammalian hosts Leishmania infantum
6.3.1.9 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

EC Number Inhibitors Comment Organism Structure
6.3.1.9 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

EC Number Metals/Ions Comment Organism Structure
6.3.1.8 Mg2+ required Leishmania infantum
6.3.1.9 Mg2+ required Leishmania infantum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.3.1.8 glutathione + spermidine + ATP Leishmania infantum
-
 glutathionylspermidine + ADP + phosphate
-
 ?
6.3.1.8 glutathione + spermidine + ATP Leishmania infantum MHOM / MA / 67 / ITMAP263
-
 glutathionylspermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + glutathionylspermidine + ATP Leishmania infantum
-
 N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + glutathionylspermidine + ATP Leishmania infantum MHOM / MA / 67 / ITMAP263
-
 N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + spermidine + ATP Leishmania infantum
-
 glutathionylspermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + spermidine + ATP Leishmania infantum MHOM / MA / 67 / ITMAP263
-
 glutathionylspermidine + ADP + phosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.3.1.8 Leishmania infantum A4I1T8
-
-
6.3.1.8 Leishmania infantum MHOM / MA / 67 / ITMAP263 A4I1T8
-
-
6.3.1.9 Leishmania infantum A4I2Z3
-
-
6.3.1.9 Leishmania infantum MHOM / MA / 67 / ITMAP263 A4I2Z3
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.3.1.8 recombinant His6-tagged enzyme solubilized from Escherichia coli strain Rosetta (DE3) inclusion bodies by nickel affinity chromatography and gel filtration Leishmania infantum
6.3.1.9 recombinant His6-tagged enzyme from Escherichia coli strain Tuner (DE3) CodonPlus by nickel affinity chromatography and gel filtration Leishmania infantum

Renatured (Commentary)

EC Number Renatured (Comment) Organism
6.3.1.8 recombinant His6-tagged enzyme from Escherichia coli strain Rosetta (DE3) inclusion bodies by solubilization with 8 M urea, 5 mM imidazole, and 1 mM 2-mercaptoethanol Leishmania infantum

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.3.1.8 additional information the extracellular promastigotes residing in the insect vector and the intracellular amastigotes thriving in mammalian hosts, expression of LiGSPS cannot be detected directly in Leishmania infantum Leishmania infantum
-
6.3.1.9 amastigote LiTRYS is constitutively expressed in Leishmania infantum axenic amastigotes Leishmania infantum
-
6.3.1.9 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
-
6.3.1.9 promastigote LiTRYS is constitutively expressed along Leishmania infantum promastigote growth Leishmania infantum
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.3.1.8 glutathione + spermidine + ATP
-
 Leishmania infantum glutathionylspermidine + ADP + phosphate
-
 ?
6.3.1.8 glutathione + spermidine + ATP
-
 Leishmania infantum MHOM / MA / 67 / ITMAP263 glutathionylspermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + glutathionylspermidine + ATP
-
 Leishmania infantum N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + glutathionylspermidine + ATP
-
 Leishmania infantum MHOM / MA / 67 / ITMAP263 N1,N8-bis(glutathionyl)spermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + spermidine + ATP
-
 Leishmania infantum glutathionylspermidine + ADP + phosphate
-
 ?
6.3.1.9 glutathione + spermidine + ATP
-
 Leishmania infantum MHOM / MA / 67 / ITMAP263 glutathionylspermidine + ADP + phosphate
-
 ?

Subunits

EC Number Subunits Comment Organism
6.3.1.9 ? x * 79000, recombinant enzyme, SDS-PAGE Leishmania infantum

Synonyms

EC Number Synonyms Comment Organism
6.3.1.8 GspS
-
 Leishmania infantum
6.3.1.8 LiGSPS
-
 Leishmania infantum
6.3.1.9 LiTRYS
-
 Leishmania infantum
6.3.1.9 trypanothione synthase
-
 Leishmania infantum
6.3.1.9 TryS
-
 Leishmania infantum

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.3.1.8 22
-
 assay at room temperature Leishmania infantum
6.3.1.9 22
-
 assay at room temperature Leishmania infantum

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.3.1.8 7.4
-
 assay at Leishmania infantum
6.3.1.9 7.4
-
 assay at Leishmania infantum

Cofactor

EC Number Cofactor Comment Organism Structure
6.3.1.8 ATP
-
 Leishmania infantum
6.3.1.9 ATP
-
 Leishmania infantum

General Information

EC Number General Information Comment Organism
6.3.1.8 physiological function glutathionylspermidine synthetase (GSPS) is capable of performing the first step of trypanothione synthesis yielding glutathionylspermidine, this monothiol can substitute for trypanothione in some reactions. But trypanothione synthetase, EC 6.3.1.9, and not glutathionylspermidine synthetase, EC 6.3.1.8, is essential for Leishmania infantum, superfluous role of enzyme GSPS. LiGSPS is not crucial for survival and replication of Leishmania infantum promastigotes and amastigotes, trypanothione synthase, TRYS, might be redundant in parasites harboring GSPS Leishmania infantum
6.3.1.9 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
6.3.1.9 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