Dihydrofolate reductase-thymidylate synthase (parasite) (DHFR-TS (when referring to the bifunctional parasite enzyme); DHFR (for the reductase domain))

Dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a bifunctional enzyme found in parasites such as Plasmodium falciparum and Plasmodium vivax, where it catalyzes two sequential reactions in folate metabolism: reduction of dihydrofolate to tetrahydrofolate and synthesis of thymidylate. The DHFR domain is essential for DNA synthesis and cell replication, making it a critical drug target in the treatment of malaria and other parasitic diseases. Selective inhibitors of parasite DHFR (antifolates like pyrimethamine and cycloguanil) block parasite growth but resistance due to point mutations in the dhfr gene is a major therapeutic challenge. The distinct sequence and structural differences between human and parasite DHFR enable the development of selective drugs, though off-target effects and resistance remain significant concerns.

Other names

Parasite dihydrofolate reductasePlasmodium dihydrofolate reductasePfDHFR (Plasmodium falciparum dihydrofolate reductase)PvDHFR (Plasmodium vivax dihydrofolate reductase)Dihydrofolate reductase (DHFR)

Inhibition of DHFR active site stops production of tetrahydrofolate and thus DNA synthesis, leading to parasite death. Antifolate agents block the folate pathway critical for parasite survival.