Dihydrofolate Reductase (Plasmodium) (DHFR)

Dihydrofolate reductase (DHFR) in Plasmodium species, including Plasmodium falciparum and Plasmodium vivax, is a critical enzyme involved in the folate pathway, essential for nucleotide biosynthesis and DNA replication. In these parasites, DHFR is part of a bifunctional enzyme complex with thymidylate synthase (TS), known as DHFR-TS. It catalyzes the NADPH-dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), which is necessary for the synthesis of purines, thymidylate, and certain amino acids. Plasmodial DHFR is targeted by antifolate drugs such as pyrimethamine and cycloguanil. Resistance arises from specific point mutations that alter inhibitor binding.

Inhibition of dihydrofolate reductase