Cloned (Comment) | Organism |
---|---|
recombinant bifunctional enzyme DHFR-TS, DNA and amino acid sequence determination and analysis, recombinant expression of His-tagged enzyme in Escherichia coli strain M15(pREP4) | Trypanosoma cruzi |
recombinant bifunctional enzyme DHFR-TS, DNA and amino acid sequence determination and analysis, recombinant expression of His-tagged enzyme in Escherichia coli strain M15(pREP4) | Leishmania braziliensis |
recombinant bifunctional enzyme DHFR-TS, DNA and amino acid sequence determination and analysis, recombinant expression of His-tagged enzyme in Escherichia coli strain M15(pREP4) | Leishmania panamensis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
atherospermidine | competitive inhibition | Leishmania braziliensis | |
atherospermidine | competitive inhibition | Leishmania panamensis | |
atherospermidine | competitive inhibition | Trypanosoma cruzi | |
isomoschatoline | competitive inhibition | Leishmania braziliensis | |
isomoschatoline | competitive inhibition | Leishmania panamensis | |
isomoschatoline | competitive inhibition | Trypanosoma cruzi | |
liriodenine | competitive inhibition | Leishmania braziliensis | |
liriodenine | competitive inhibition | Leishmania panamensis | |
liriodenine | competitive inhibition | Trypanosoma cruzi | |
melosmine | competitive inhibition | Leishmania braziliensis | |
melosmine | competitive inhibition | Leishmania panamensis | |
melosmine | competitive inhibition | Trypanosoma cruzi | |
methotrexate | competitive inhibition | Leishmania braziliensis | |
methotrexate | competitive inhibition | Leishmania panamensis | |
methotrexate | competitive inhibition | Trypanosoma cruzi | |
additional information | inhibitory effect of antifolate drugs on enzymatic activity, and inhibitory activity of four aporphine alkaloids from Rollinia pittieri and Pseudomalmea boyacana, and some 2,4-diamino-pyrimidine antifolates, overview | Leishmania braziliensis | |
additional information | inhibitory effect of antifolate drugs on enzymatic activity, and inhibitory activity of four aporphine alkaloids from Rollinia pittieri and Pseudomalmea boyacana, and some 2,4-diamino-pyrimidine antifolates, overview | Leishmania panamensis | |
additional information | inhibitory effect of antifolate drugs on enzymatic activity, and inhibitory activity of four aporphine alkaloids from Rollinia pittieri and Pseudomalmea boyacana, and some 2,4-diamino-pyrimidine antifolates, overview | Trypanosoma cruzi | |
pyrimethamine | competitive inhibition | Leishmania braziliensis | |
pyrimethamine | competitive inhibition | Leishmania panamensis | |
pyrimethamine | competitive inhibition | Trypanosoma cruzi | |
trimethoprim | competitive inhibition | Leishmania braziliensis | |
trimethoprim | competitive inhibition | Leishmania panamensis | |
trimethoprim | competitive inhibition | Trypanosoma cruzi |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | Michaelis-Menten kinetics | Leishmania braziliensis | |
0.0556 | - |
7,8-dihydrofolate | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,8-dihydrofolate + NADPH + H+ | Trypanosoma cruzi | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
7,8-dihydrofolate + NADPH + H+ | Leishmania braziliensis | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
7,8-dihydrofolate + NADPH + H+ | Leishmania panamensis | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Leishmania braziliensis | A4H4P8 | - |
- |
Leishmania panamensis | S5M3K7 | - |
- |
Trypanosoma cruzi | Q27793 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged enzyme from Escherichia coli strain M15(pREP4) by nickel affinity chromatography | Trypanosoma cruzi |
recombinant His-tagged enzyme from Escherichia coli strain M15(pREP4) by nickel affinity chromatography | Leishmania braziliensis |
recombinant His-tagged enzyme from Escherichia coli strain M15(pREP4) by nickel affinity chromatography | Leishmania panamensis |
Storage Stability | Organism |
---|---|
-20°C, purified recombinant protein, stable at pH 6.0 over a period of 1 month | Trypanosoma cruzi |
-20°C, purified recombinant protein, stable at pH 6.0 over a period of 1 month | Leishmania braziliensis |
-20°C, purified recombinant protein, stable at pH 6.0 over a period of 1 month | Leishmania panamensis |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
7,8-dihydrofolate + NADPH + H+ | - |
Trypanosoma cruzi | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
7,8-dihydrofolate + NADPH + H+ | - |
Leishmania braziliensis | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
7,8-dihydrofolate + NADPH + H+ | - |
Leishmania panamensis | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r |
Subunits | Comment | Organism |
---|---|---|
? | x * 58000, recombinant bifunctional enzyme DHFR-TS, SDS-PAGE | Trypanosoma cruzi |
? | x * 58000, recombinant bifunctional enzyme DHFR-TS, SDS-PAGE | Leishmania braziliensis |
? | x * 58000, recombinant bifunctional enzyme DHFR-TS, SDS-PAGE | Leishmania panamensis |
Synonyms | Comment | Organism |
---|---|---|
DHFR-TS | - |
Trypanosoma cruzi |
DHFR-TS | - |
Leishmania braziliensis |
DHFR-TS | - |
Leishmania panamensis |
dihydrofolate reductase-thymidylate synthase | - |
Trypanosoma cruzi |
dihydrofolate reductase-thymidylate synthase | - |
Leishmania braziliensis |
dihydrofolate reductase-thymidylate synthase | - |
Leishmania panamensis |
LBRM_06_0830 | - |
Leishmania braziliensis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
28 | - |
assay at | Trypanosoma cruzi |
28 | - |
assay at | Leishmania braziliensis |
28 | - |
assay at | Leishmania panamensis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
6 | - |
assay at | Trypanosoma cruzi |
6 | - |
assay at | Leishmania braziliensis |
6 | - |
assay at | Leishmania panamensis |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Trypanosoma cruzi | |
NADP+ | - |
Leishmania braziliensis | |
NADP+ | - |
Leishmania panamensis | |
NADPH | - |
Trypanosoma cruzi | |
NADPH | - |
Leishmania braziliensis | |
NADPH | - |
Leishmania panamensis |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | inhibition kinetics | Leishmania braziliensis | |
0.022 | - |
methotrexate | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | |
0.033 | - |
trimethoprim | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | |
0.068 | - |
pyrimethamine | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | |
0.717 | - |
isomoschatoline | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | |
0.748 | - |
atherospermidine | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | |
1.26 | - |
melosmine | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | |
2.615 | - |
liriodenine | pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0015 | - |
pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | methotrexate | |
0.0125 | - |
pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | pyrimethamine | |
0.152 | - |
pH 6.0, 28°C, recombinant enzyme | Leishmania braziliensis | trimethoprim |
General Information | Comment | Organism |
---|---|---|
evolution | dihydrofolate reductase (DHFR) and thymidylate synthase (TS) have undergone a fusion event generating a single polypeptide but conserving the two functions in trypanosomatids | Trypanosoma cruzi |
evolution | dihydrofolate reductase (DHFR) and thymidylate synthase (TS) have undergone a fusion event generating a single polypeptide but conserving the two functions in trypanosomatids | Leishmania braziliensis |
evolution | dihydrofolate reductase (DHFR) and thymidylate synthase (TS) have undergone a fusion event generating a single polypeptide but conserving the two functions in trypanosomatids | Leishmania panamensis |
physiological function | dihydrofolate reductase is an essential enzyme in the tetrahydrofolate pathway which catalyzes the NADPH-dependent reduction of 7,8-dihydrofolate (H2F) to the 5,6,7,8-tetrahydrofolate needed to maintain intracellular pools of tetrahydrofolate and its derivatives. These are essential cofactors in the biosynthesis of purines, pyrimidines and several amino acids | Trypanosoma cruzi |
physiological function | dihydrofolate reductase is an essential enzyme in the tetrahydrofolate pathway which catalyzes the NADPH-dependent reduction of 7,8-dihydrofolate (H2F) to the 5,6,7,8-tetrahydrofolate needed to maintain intracellular pools of tetrahydrofolate and its derivatives. These are essential cofactors in the biosynthesis of purines, pyrimidines and several amino acids | Leishmania braziliensis |
physiological function | dihydrofolate reductase is an essential enzyme in the tetrahydrofolate pathway which catalyzes the NADPH-dependent reduction of 7,8-dihydrofolate (H2F) to the 5,6,7,8-tetrahydrofolate needed to maintain intracellular pools of tetrahydrofolate and its derivatives. These are essential cofactors in the biosynthesis of purines, pyrimidines and several amino acids | Leishmania panamensis |