Literature summary for 1.5.1.3 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.

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Protein Variants

Protein Variants	Comment	Organism
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

Organism	UniProt	Comment	Textmining
Plasmodium falciparum	P13922	bifunctional thymidylate synthase-dihydrofolate reductase	-

Reaction

Reaction	Comment	Organism	Reaction ID
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

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Release 2023.1 (January 2023)