Dihydrofolate reductase from Plasmodium falciparum (DHFR (commonly "PfDHFR" to specify Plasmodium falciparum))

Dihydrofolate reductase from Plasmodium falciparum is an essential enzyme that maintains the folate cycle, required for the synthesis of thymidine and ultimately DNA. It catalyzes the reduction of dihydrofolate to tetrahydrofolate using NADPH as a donor, a step crucial for cell division and proliferation in the malaria parasite. This enzyme is structurally distinct from its mammalian counterpart, which has enabled the development of selective inhibitors used in malaria therapy, such as pyrimethamine and cycloguanil. However, the effectiveness of these drugs has been undermined by rapid emergence of resistant parasite strains harboring point mutations in the DHFR gene, necessitating ongoing drug development efforts that address both wild-type and mutant forms of the enzyme.

Other names

Bifunctional thymidylate synthase–dihydrofolate reductase (TS-DHFR)Plasmodium falciparum DHFRPfDHFR

Competitive inhibition of DHFR, blocking the reduction of dihydrofolate to tetrahydrofolate, thereby halting DNA synthesis and parasite replication