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Literature summary for 6.3.2.12 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
Search for more literature for 6.3.2.12

Application

Application Comment Organism
medicine target for antimalarial therapy Plasmodium falciparum

Cloned(Commentary)

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

Inhibitors

Inhibitors Comment Organism Structure
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
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
additional information not inhibitory: methotrexate Plasmodium falciparum

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
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
0.00088
-
 dihydropteroate
-
 Plasmodium falciparum
0.00088
-
 dihydropteroate pH 10.0, 37°C Plasmodium falciparum
0.00597
-
 glutamate
-
 Plasmodium falciparum
0.006
-
 L-Glu pH 10.0, 37°C Plasmodium falciparum
0.0228
-
 ATP
-
 Plasmodium falciparum
0.0228
-
 ATP pH 10.0, 37°C Plasmodium falciparum

Molecular Weight [Da]

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

Organism

Organism UniProt Comment Textmining
Plasmodium falciparum
-
-
-
Plasmodium falciparum
-
 bifunctional dihydrofolate synthase-folylpolyglutamate synthase
-

Purification (Commentary)

Purification (Comment) Organism
-
 Plasmodium falciparum

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + 7,8-dihydropteroate + L-Glu
-
 Plasmodium falciparum ADP + phosphate + 7,8-dihydrofolate
-
 ?
ATP + L-glutamate + 7,8-dihydropteroate assay at pH 10, 37°C Plasmodium falciparum ADP + phosphate + 7,8-dihydropteroylglutamate
-
 ?

Subunits

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

Synonyms

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

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Plasmodium falciparum

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
10
-
 assay at Plasmodium falciparum

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00014
-
 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid
-
 Plasmodium falciparum
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
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

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000041
-
-
 Plasmodium falciparum 2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid

Expression

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