Toxoplasma gondii dihydrofolate reductase-thymidylate synthase (TgDHFR-TS)

Toxoplasma gondii dihydrofolate reductase-thymidylate synthase is a bifunctional enzyme found in the protozoan parasite T. gondii and catalyzes two consecutive steps in the folate pathway: the reduction of dihydrofolate to tetrahydrofolate (DHFR activity) and the methylation of deoxyuridylate to deoxythymidylate (thymidylate synthase activity) on a single polypeptide chain[6][1][2]. This enzyme is essential for de novo DNA synthesis and cell proliferation, making it a validated therapeutic target for toxoplasmosis[5][6]. Inhibitors of DHFR, like pyrimethamine, have been widely used to treat infection, though challenges include drug resistance and host toxicity due to structural similarities between parasitic and human enzymes[4][5]. The unique structural and kinetic characteristics of the T. gondii bifunctional enzyme, distinct from human monofunctional enzymes, present opportunities for species-selective drug development[1][2][4].

Other names

Toxoplasma gondii DHFR-TSTgDHFR-TSBifunctional dihydrofolate reductase-thymidylate synthase (T. gondii)

Inhibition of folate pathway, blocking DNA synthesis in the parasite; Inhibition of dihydrofolate reduction; Inhibition of thymidylate synthesis