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Dihydrofolate Reductase-Thymidylate Synthase (Plasmodium species) (DHFR-TS)
- Target
- DHFR-TS
- Molecular classification
- Enzyme, Multifunctional enzyme
01
Overview
Dihydrofolate reductase (DHFR) is a critical enzyme in the folate pathway of Plasmodium species, including *Plasmodium falciparum*, *P. vivax*, *P. malariae*, and others. It catalyzes the NADPH-dependent reduction of dihydrofolate (H₂-folate) to tetrahydrofolate (H₄-folate), which is essential for de novo nucleotide synthesis and thus for DNA replication and cell division. In Plasmodium, DHFR exists as part of a bifunctional enzyme with thymidylate synthase (TS), known as DHFR-TS, encoded by a single gene. It is a validated antimalarial drug target, but resistance arises through point mutations.
- Other names
- Plasmodium dihydrofolate reductase-thymidylate synthaseDHFRTS
02
Mechanism of action
Inhibition of dihydrofolate reductase activity, leading to disruption of folate metabolism and nucleotide biosynthesis
03
Biological functions
Folate recyclingNucleotide biosynthesisDNA replicationCell division
04
Disease associations
Infection
05
Safety considerations
Toxicity due to inhibition of human DHFRDevelopment of drug resistance
06
Interacting drugs
Pyrimethamine
1 more in the full profile.
07
Biomarkers
dhfr mutations (codons 16, 51, 59, 108, 164)
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