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Literature summary extracted from

  • Hamilton, D.; Wu, J.H.; Alaoui-Jamali, M.; Batist, G.
    A novel missense mutation in the gamma-glutamylcysteine synthetase catalytic subunit gene causes both decreased enzymatic activity and glutathione production (2003), Blood, 102, 725-730.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.3.2.2 catalytic subunit DNA sequence determination and analysis, expression as His-tagged wild-type enzyme and mutant R127C in Rosetta cells, functional expression of wild-type and mutant enzyme in enzyme-deficient cells Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
6.3.2.2 R127C naturally occuring mutation in patients with hemolytic anemia resulting from low erythrocyte enzyme levels, fibroblast cells from these patients bearing the mutation show 95% reduced enzyme activity and lowered Km for glutamate and aminobutyrate, as well as an increased Ki for GSH Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.3.2.2 GSH feedback inhibition, mutant R127C is not sensitive Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
6.3.2.2 0.25
-
 L-alpha-aminobutyrate mutant R127C, pH 8.0, 37°C Homo sapiens
6.3.2.2 0.63
-
 L-Glu mutant R127C, pH 8.0, 37°C Homo sapiens
6.3.2.2 2.39
-
 L-alpha-aminobutyrate wild-type enzyme, pH 8.0, 37°C Homo sapiens
6.3.2.2 7.16
-
 L-Glu wild-type enzyme, pH 8.0, 37°C Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
6.3.2.2 Mg2+
-
 Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.3.2.2 ATP + L-Glu + L-Cys Homo sapiens first and rate limiting step in GSH biosynthesis, rare hereditary enzyme deficiency is associated with low erythrocyte levels of the enzyme leading to hemolytic anemia ADP + phosphate + gamma-L-Glu-L-Cys
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.3.2.2 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.3.2.2 recombinant His-tagged wild-type and mutant R127C enzyme from Rosetta cells Homo sapiens

Reaction

EC Number Reaction Comment Organism Reaction ID
6.3.2.2 ATP + L-glutamate + L-cysteine = ADP + phosphate + gamma-L-glutamyl-L-cysteine substrate binding mechanism and catalytic site structure determination and analysis, Arg127 and conserved Cys249 are involved Homo sapiens
a

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.3.2.2 fibroblast dermal Homo sapiens
-

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
6.3.2.2 0.44
-
 purified mutant R127C enzyme, substrates L-glutamate and L-alpha-aminobutyrate Homo sapiens
6.3.2.2 8.86
-
 purified wild-type enzyme, substrates L-glutamate and L-alpha-aminobutyrate Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.3.2.2 ATP + L-Glu + L-alpha-aminobutyrate
-
 Homo sapiens ADP + phosphate + gamma-L-Glu-L-alpha-aminobutyrate
-
 ?
6.3.2.2 ATP + L-Glu + L-Cys
-
 Homo sapiens ADP + phosphate + gamma-L-Glu-L-Cys
-
 ?
6.3.2.2 ATP + L-Glu + L-Cys first and rate limiting step in GSH biosynthesis, rare hereditary enzyme deficiency is associated with low erythrocyte levels of the enzyme leading to hemolytic anemia Homo sapiens ADP + phosphate + gamma-L-Glu-L-Cys
-
 ?

Subunits

EC Number Subunits Comment Organism
6.3.2.2 More the holoenzyme consists of a heavy catalytic and a light modifier subunit, i.e. gamma-GCSH and gamma-GCSL, protein modeling Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
6.3.2.2 gamma-GCS
-
 Homo sapiens
6.3.2.2 gamma-Glutamylcysteine synthetase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.3.2.2 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.3.2.2 8
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
6.3.2.2 ATP dependent on Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
6.3.2.2 0.45
-
 GSH wild-type enzyme, pH 8.0, 37°C Homo sapiens
6.3.2.2 1000
-
 GSH above, mutant R127C, pH 8.0, 37°C Homo sapiens