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Literature summary for 1.5.1.3 extracted from
- Expression, purification and enzymatic characterization of Brugia malayi dihydrofolate reductase (2016), Protein Expr. Purif., 128, 81-85 .
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | dihydrofolate reductase is a potential drug target for the elimination of Brugia malayi, one of the three causative agents of lymphatic filariasis, a parasitic disease | Brugia malayi |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| sequence comparisons, recombinant expression of His6-tagged enzyme in Escherichia coli strain BL21(DE3) | Brugia malayi |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 2,4-diaminopyrimidine | poor inhibition | Brugia malayi |  |
| 2,4-diaminoquinazoline | low inhibition | Brugia malayi | |
| cycloguanil | low inhibition | Brugia malayi | |
| methotrexate | strong inhibition | Brugia malayi | |
| additional information | antifolate compounds can serve as inhibitors of BmDHFR | Brugia malayi | |
| pyrimethamine | - |
Brugia malayi | |
| trimethoprim | - |
Brugia malayi | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | Michaelis-Menten steady-state kinetics | Brugia malayi | |
| 0.0147 | - |
7,8-dihydrofolate | above, pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 7,8-dihydrofolate + NADPH + H+ | Brugia malayi | - |
5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Brugia malayi | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography | Brugia malayi |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 7,8-dihydrofolate + NADPH + H+ | - |
Brugia malayi | 5,6,7,8-tetrahydrofolate + NADP+ | - |
r | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 22000, recombinant His6-tagged enzyme, SDS-PAGE, x * 22086, sequence calculation, His-tagged enzyme | Brugia malayi |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| BmDHFR | - |
Brugia malayi |
| DHFR | - |
Brugia malayi |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 25 | - |
assay at | Brugia malayi |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 1.4 | - |
7,8-dihydrofolate | above, pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 6 | - |
assay at | Brugia malayi |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADP+ | - |
Brugia malayi | |
| NADPH | the equilibrium dissociation constant KD for NADPH is 25nM | Brugia malayi | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | inhibition kinetics | Brugia malayi | |
| 0.0000013 | - |
methotrexate | pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
| 0.013 | - |
pyrimethamine | pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
| 0.046 | - |
trimethoprim | pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
| 0.065 | - |
2,4-diaminopyrimidine | pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
| 0.459 | - |
2,4-diaminoquinazoline | pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
| 8 | - |
cycloguanil | above, pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.0000031 | - |
pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | methotrexate | |
| 0.032 | - |
pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | trimethoprim | |
| 0.109 | - |
pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | pyrimethamine | |
| 0.154 | - |
pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | 2,4-diaminoquinazoline | |
| 0.771 | - |
pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | cycloguanil | |
| 20 | - |
above, pH 6.0, 25°C recombinant His-tagged enzyme | Brugia malayi | 2,4-diaminopyrimidine | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| additional information | the predicted specificity determining positions in BmDHFR for ligand binding are Val5, Gly12, Met27, Asn44, Ala45, Lys51, Phe60, Val84, Phe89 Leu95, Leu96, Gly133, Ala137, Val139, Phe140, Phe141 and Glu169 | Brugia malayi |
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