Target intelligence / Profile preview

Dihydrofolate Reductase (Plasmodium falciparum) (None)

Target
None
Molecular classification
Enzyme
01

Overview

Dihydrofolate reductase (DHFR) from *Plasmodium falciparum* is a key enzyme in the folate metabolic pathway, essential for DNA synthesis and cell proliferation. In *P. falciparum*, DHFR exists as part of a bifunctional enzyme with thymidylate synthase (TS), known as DHFR-TS, which is critical for de novo nucleotide biosynthesis and thus parasite survival. It catalyzes the NADPH-dependent reduction of dihydrofolate to tetrahydrofolate, required for the synthesis of purines, thymidylate, glycine, and methionine. Resistance to antifolate drugs, like pyrimethamine and cycloguanil, is common due to point mutations in the DHFR domain.

02

Mechanism of action

Inhibition of dihydrofolate reductase, leading to disruption of DNA synthesis and cell proliferation.

03

Biological functions

Folate metabolismDe novo purine biosynthesisThymidylate biosynthesisDNA precursor synthesisCell proliferation
04

Disease associations

Infection
05

Safety considerations

Drug resistancePotential for off-target effects on human DHFR
06

Interacting drugs

Pyrimethamine

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