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Literature summary extracted from

  • McGuire, J.J.; Haile, W.H.; Valiaeva, N.; Bartley, D.; Guo, J.; Coward, J.K.
    Potent inhibition of human folylpolyglutamate synthetase by a phosphinic acid mimic of the tetrahedral reaction intermediate (2003), Biochem. Pharmacol., 65, 315-318.
    View publication on PubMed

Application

EC Number Application Comment Organism
6.3.2.17 medicine the enzyme inhibition can be useful for cancer chemotherapy Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.3.2.17 expression in Sf9 insect cells Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.3.2.17 methotrexate-phosphinate competitive inhibition, IC50 of 0.000008 mM, at fixed substrate and recombinant enzyme concentrations. The most potent FPGS inhibitor based on methotrexate heterocycle. CCRF-CEM R2 subline does not respond to inhibition by this compound at 0.001 mM Homo sapiens
6.3.2.17 methotrexate-phosphonate IC50 0.00012 mM, at fixed substrate and recombinant enzyme concentrations Homo sapiens
6.3.2.17 additional information no inhibition by methotrexate in the CCRF-CEM R2 cell subline Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
6.3.2.17 additional information Homo sapiens the enzyme synthesizes folate and antifolate poly(gamma-glutamate) metabolites ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
6.3.2.17 Homo sapiens
-
 human
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.3.2.17 ammonium sulfate fractionation and chromatography on BioGel A-0.5M, recombinant enzyme Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
6.3.2.17 CCRF-CEM cell T-lymphoblastic leukemia line, wild type cell line and its methrotrexate transport-deficient subline R2 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.3.2.17 ATP + methotrexate-Glu + L-glutamate
-
 Homo sapiens ADP + methotrexate-Glu2 + phosphate
-
 ?
6.3.2.17 ATP + methotrexate-phosphinate + L-glutamate
-
 Homo sapiens ?
-
 ?
6.3.2.17 ATP + methotrexate-phosphonate + L-glutamate
-
 Homo sapiens ?
-
 ?
6.3.2.17 additional information the enzyme synthesizes folate and antifolate poly(gamma-glutamate) metabolites Homo sapiens ?
-
 ?

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
6.3.2.17 0.0000031
-
 methotrexate-phosphinate Kis value, with methrotrexate as variable substrate, for recombinant enzyme Homo sapiens
6.3.2.17 0.000056
-
 methotrexate-phosphinate Kii value, with methotrexate as variable substrate, for recombinant enzyme Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
6.3.2.17 0.000008
-
 competitive inhibition, IC50 of 0.000008 mM, at fixed substrate and recombinant enzyme concentrations. The most potent FPGS inhibitor based on methotrexate heterocycle. CCRF-CEM R2 subline does not respond to inhibition by this compound at 0.001 mM Homo sapiens methotrexate-phosphinate
6.3.2.17 0.00012
-
 IC50 0.00012 mM, at fixed substrate and recombinant enzyme concentrations Homo sapiens methotrexate-phosphonate