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