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Literature summary for 2.1.1.45 extracted from
- Biochemical characterization of the bifunctional enzyme dihydrofolate reductase-thymidylate synthase from Leishmania (Viannia) and its evaluation as a drug target (2013), Biomedica, 33, 393-401 .
Cloned(Commentary)
| 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
| 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 [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten kinetics | Leishmania braziliensis |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methylenetetrahydrofolate + dUMP | Trypanosoma cruzi | - |
dihydrofolate + dTMP | - |
? | |
| 5,10-methylenetetrahydrofolate + dUMP | Leishmania braziliensis | - |
dihydrofolate + dTMP | - |
? | |
| 5,10-methylenetetrahydrofolate + dUMP | Leishmania panamensis | - |
dihydrofolate + dTMP | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Leishmania braziliensis | A4H4P8 | - |
- |
| Leishmania braziliensis | A4H4P8 | subsp. viannia | - |
| Leishmania panamensis | S5M3K7 | - |
- |
| Trypanosoma cruzi | Q27793 | - |
- |
Purification (Commentary)
| 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
| 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 and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5,10-methylenetetrahydrofolate + dUMP | - |
Trypanosoma cruzi | dihydrofolate + dTMP | - |
? | |
| 5,10-methylenetetrahydrofolate + dUMP | - |
Leishmania braziliensis | dihydrofolate + dTMP | - |
? | |
| 5,10-methylenetetrahydrofolate + dUMP | - |
Leishmania panamensis | dihydrofolate + dTMP | - |
? | |
Subunits
| 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
| 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 [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 28 | - |
assay at | Trypanosoma cruzi |
| 28 | - |
assay at | Leishmania braziliensis |
| 28 | - |
assay at | Leishmania panamensis |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 6 | - |
assay at | Trypanosoma cruzi |
| 6 | - |
assay at | Leishmania braziliensis |
| 6 | - |
assay at | Leishmania panamensis |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | DHFR inhibition kinetics | Leishmania braziliensis |
General Information
| 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 |
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