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Literature summary extracted from

  • Wang, P.; Wang, Q.; Yang, Y.; Coward, J.K.; Nzila, A.; Sims, P.F.; Hyde, J.E.
    Characterisation of the bifunctional dihydrofolate synthase-folylpolyglutamate synthase from Plasmodium falciparum; a potential novel target for antimalarial antifolate inhibition (2010), Mol. Biochem. Parasitol., 172, 41-51.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
6.3.2.12 medicine target for antimalarial therapy Plasmodium falciparum
6.3.2.17 medicine target for antimalarial therapy Plasmodium falciparum

Cloned(Commentary)

EC Number Cloned (Comment) Organism
6.3.2.12 expression in Escherichia coli BL21 cells Plasmodium falciparum
6.3.2.12 expression of His-tagged protein in Escherichia coli Plasmodium falciparum
6.3.2.17 expression in Escherichia coli BL21 cells Plasmodium falciparum

Inhibitors

EC Number Inhibitors Comment Organism Structure
6.3.2.12 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid selective for dihydrofolate synthase activity Plasmodium falciparum
6.3.2.12 2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum
6.3.2.12 additional information not inhibitory: methotrexate Plasmodium falciparum
6.3.2.17 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum
6.3.2.17 2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
6.3.2.12 additional information
-
 additional information non-standard kinetics at high glutamate and ATP concentrations, being partially inhibited by increasing concentrations of its principal substrate, dihydropteroate. Binding of dihydropteroate to the catalytic and inhibitory sites exhibits dissociation constants of 0.50 microM and 1.25 microM, respectively. Under lower co-substrate concentrations, data fit the Michaelis-Menten equation Plasmodium falciparum
6.3.2.12 0.00088
-
 dihydropteroate
-
 Plasmodium falciparum
6.3.2.12 0.00088
-
 dihydropteroate pH 10.0, 37°C Plasmodium falciparum
6.3.2.12 0.00597
-
 glutamate
-
 Plasmodium falciparum
6.3.2.12 0.006
-
 L-Glu pH 10.0, 37°C Plasmodium falciparum
6.3.2.12 0.0228
-
 ATP
-
 Plasmodium falciparum
6.3.2.12 0.0228
-
 ATP pH 10.0, 37°C Plasmodium falciparum
6.3.2.17 0.00096
-
 5,6,7,8-tetrahydrofolate
-
 Plasmodium falciparum

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
6.3.2.12 62000
-
 1 * 62400, calculated for His-tagged recombinant protein, 1 * 62000, SDS-PAGE Plasmodium falciparum
6.3.2.12 62400
-
 1 * 62400, calculated for His-tagged recombinant protein, 1 * 62000, SDS-PAGE Plasmodium falciparum
6.3.2.12 90000
-
 gel filtration, His-tagged recombinant protein Plasmodium falciparum

Organism

EC Number Organism UniProt Comment Textmining
6.3.2.12 Plasmodium falciparum
-
-
-
6.3.2.12 Plasmodium falciparum
-
 bifunctional dihydrofolate synthase-folylpolyglutamate synthase
-
6.3.2.17 Plasmodium falciparum
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
6.3.2.12
-
 Plasmodium falciparum
6.3.2.17
-
 Plasmodium falciparum

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
6.3.2.12 ATP + 7,8-dihydropteroate + L-Glu
-
 Plasmodium falciparum ADP + phosphate + 7,8-dihydrofolate
-
 ?
6.3.2.12 ATP + L-glutamate + 7,8-dihydropteroate assay at pH 10, 37°C Plasmodium falciparum ADP + phosphate + 7,8-dihydropteroylglutamate
-
 ?
6.3.2.17 ATP + 5,6,7,8-tetrahydrofolate + L-glutamate
-
 Plasmodium falciparum ADP + phosphate + 5,6,7,8-tetrahydrofolyl-Glu
-
 ?
6.3.2.17 ATP + L-glutamate + tetrahydrofolate-Glu assay at pH 10, 37°C Plasmodium falciparum ADP + phosphate + tetrahydrofolyl-Glu2
-
 ?

Subunits

EC Number Subunits Comment Organism
6.3.2.12 monomer
-
 Plasmodium falciparum
6.3.2.12 monomer 1 * 62400, calculated for His-tagged recombinant protein, 1 * 62000, SDS-PAGE Plasmodium falciparum
6.3.2.17 monomer
-
 Plasmodium falciparum

Synonyms

EC Number Synonyms Comment Organism
6.3.2.12 DHFS
-
 Plasmodium falciparum
6.3.2.12 dihydrofolate synthase
-
 Plasmodium falciparum
6.3.2.12 PfDHFS-FPGS bifunctional protein together with folypolyglutamate synthase, EC 6.3.2.17 Plasmodium falciparum
6.3.2.17 folypolyglutamate synthase
-
 Plasmodium falciparum
6.3.2.17 FPGS
-
 Plasmodium falciparum
6.3.2.17 PfDHFS-FPGS bifunctional protein together with dihydrofolate synthase, EC 6.3.2.12 Plasmodium falciparum

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
6.3.2.12 37
-
 assay at Plasmodium falciparum
6.3.2.17 37
-
 assay at Plasmodium falciparum

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
6.3.2.12 10
-
 assay at Plasmodium falciparum
6.3.2.17 10
-
 assay at Plasmodium falciparum

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
6.3.2.12 0.00014
-
 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum
6.3.2.12 0.00014
-
 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid pH 10.0, 37°C Plasmodium falciparum
6.3.2.12 0.00169
-
 2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum
6.3.2.17 0.000091
-
 2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum
6.3.2.17 0.00063
-
 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
6.3.2.12 0.000041
-
-
 Plasmodium falciparum 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
6.3.2.17 0.00039
-
-
 Plasmodium falciparum 2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid

Expression

EC Number Organism Comment Expression
6.3.2.12 Plasmodium falciparum expressed as single bifunctional protein with folypolyglutamate synthase, EC 6.3.2.17 additional information
6.3.2.17 Plasmodium falciparum expressed as single bifunctional protein with dihydrofolate synthase, EC 6.3.2.12 additional information