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Literature summary extracted from

  • Dasgupta, T.; Anderson, K.S.
    Probing the role of parasite-specific, distant structural regions on communication and catalysis in the bifunctional thymidylate synthase-dihydrofolate reductase from Plasmodium falciparum (2008), Biochemistry, 47, 1336-1345.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.1.1.45 expressed in Escherichia coli BL21(DE3) cells Plasmodium falciparum

Protein Variants

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

Organism

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
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.1.1.45
-
 Plasmodium falciparum

Reaction

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
a

Substrates and Products (Substrate)

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
-
 ?

Synonyms

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

Turnover Number [1/s]

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

Cofactor

EC Number Cofactor Comment Organism Structure
2.1.1.45 N5,N10-methylenetetrahydrofolate
-
 Plasmodium falciparum