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Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase (PfDHFR-TS)
- Target
- PfDHFR-TS
- Molecular classification
- Enzyme, Lyase
01
Overview
Plasmodium falciparum bifunctional dihydrofolate reductase-thymidylate synthase (PfDHFR-TS) is a key enzyme in the folate biosynthesis pathway of the malaria parasite. It catalyzes two sequential reactions essential for DNA synthesis and cell proliferation: reduction of dihydrofolate to tetrahydrofolate (DHFR activity) and methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) using methylene tetrahydrofolate as a cofactor. Unlike humans, where DHFR and TS are separate proteins, P. falciparum expresses these activities on a single polypeptide chain, making PfDHFR-TS bifunctional. It is a validated antimalarial drug target, but resistance has emerged.
- Other names
- DHFR-TSDihydrofolate reductase-thymidylate synthase
02
Mechanism of action
Inhibition of dihydrofolate reductase and thymidylate synthase activities, leading to disruption of DNA synthesis and cell proliferation in Plasmodium falciparum.
03
Biological functions
Folate MetabolismNucleotide BiosynthesisCell Proliferation
04
Disease associations
Infection
05
Safety considerations
Drug resistance due to point mutations in the DHFR active site.
06
Interacting drugs
Pyrimethamine
2 more in the full profile.
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