The structure of Plasmodium falciparum serine hydroxymethyltransferase reveals a novel redox switch that regulates its activities

摘要: Plasmodium falciparum serine hydroxymethyltransferase (PfSHMT), an enzyme in the dTMP synthesis cycle, is antimalarial target because inhibition of its expression or function has been shown to be lethal parasite. As wild-type could not crystallized, protein engineering residues on surface was carried out. The surface-engineered mutant PfSHMT-F292E successfully crystallized and structure determined at 3 A resolution. a good representation PfSHMT as this variant revealed biochemical properties similar those wild type. Although overall other SHMTs, unique features including presence two loops distinctive cysteine pair formed by Cys125 Cys364 tetrahydrofolate (THF) substrate binding pocket were identified. These structural characteristics have never reported SHMTs. Biochemical characterization mutation analysis these confirm that they act disulfide/sulfhydryl switch regulate THF-dependent catalytic enzyme. This redox present human enzyme, which absent. data here can further exploited new strategy specifically disrupt activity parasite without interfering with