EC Number | Cloned (Comment) | Organism |
---|---|---|
2.1.1.45 | expressed in Escherichia coli BL21(DE3) cells | Plasmodium falciparum |
EC Number | Protein Variants | Comment | Organism |
---|---|---|---|
1.5.1.3 | additional information | deletion mutant lacking residues 2-5 of N-terminal tail compared to an analogous deletion of residues 2-22 of the N-terminal tail and construction of a mutant in the crossover helix that interacts with the dihydrofolate reductase active site by substitution of its five residues with alanines to form the Ala-FACE helix mutant. Mutations to the linker region within the bifunctional thymidylate synthase-dihydrofolate reductase affect neither catalytic rate nor domain-domain communication. Deletion of the N-terminal tail, although in a location remote from the active site, decreases the dihydrofolate reductase single rate and the bifunctional thymidylate synthase-dihydrofolate reductase rate by a factor of 2. The 2-fold activation of the dihydrofolate reductase rate by thymidylate synthase ligands remains intact, although even the activated N-terminal mutant has just half the dihydrolfolate reductase activity of the wild-type enzyme. However, the reciprocal communication between thymidlyate synthase active site and dihydrolfolate reductase ligands is impaired in N-terminal mutants | Plasmodium falciparum |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
1.5.1.3 | Plasmodium falciparum | P13922 | bifunctional thymidylate synthase-dihydrofolate reductase | - |
2.1.1.45 | Plasmodium falciparum | P13922 | - |
- |
2.1.1.45 | Plasmodium falciparum TM4/8.2 | P13922 | - |
- |
EC Number | Purification (Comment) | Organism |
---|---|---|
2.1.1.45 | - |
Plasmodium falciparum |
EC Number | Reaction | Comment | Organism | Reaction ID |
---|---|---|---|---|
1.5.1.3 | 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ | in Plasmodium bifunctional thymidylate synthase-dihydrofolate reductase, the overall rate-limiting step is thymidylate synthase catalysis.If thymidylate synthase is in an activated liganded conformation, the dihydrofolate reductase is 2-fold activated. The thymidylate synthase rate is also reciprocally activated by 1.5-fold if dihydrolfolate reductase is in an activated, ligand-bound conformation | Plasmodium falciparum |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
2.1.1.45 | 5,10-methylenetetrahydrofolate + dUMP | - |
Plasmodium falciparum | dihydrofolate + dTMP | - |
? | |
2.1.1.45 | 5,10-methylenetetrahydrofolate + dUMP | - |
Plasmodium falciparum TM4/8.2 | dihydrofolate + dTMP | - |
? |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
2.1.1.45 | thymidylate synthase-dihydrofolate reductase | bifunctional enzyme | Plasmodium falciparum |
2.1.1.45 | TS-DHFR | - |
Plasmodium falciparum |
EC Number | Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|---|
2.1.1.45 | 0.84 | - |
5,10-methylenetetrahydrofolate | D4 N-terminal tail mutant enzyme | Plasmodium falciparum | |
2.1.1.45 | 1.2 | - |
5,10-methylenetetrahydrofolate | wild type enzyme | Plasmodium falciparum | |
2.1.1.45 | 1.4 | - |
5,10-methylenetetrahydrofolate | Ala-FACE mutant enzyme with residues 284, 285, 288, 289, and 292 mutated to Ala | Plasmodium falciparum |
EC Number | Cofactor | Comment | Organism | Structure |
---|---|---|---|---|
2.1.1.45 | N5,N10-methylenetetrahydrofolate | - |
Plasmodium falciparum |