Plasmodium falciparum GPI-anchored wall transfer protein 1 (PfGWT1)

Plasmodium falciparum GPI-anchored wall transfer protein 1 (PfGWT1) is an essential enzyme in the glycosylphosphatidylinositol (GPI) biosynthesis pathway of the malaria parasite [1, 2]. It acts as an inositol acyltransferase, catalyzing the transfer of an acyl group to the inositol ring of the GPI precursor, a step that is mandatory for the subsequent addition of mannose residues [4, 10]. This process is critical for the anchoring of major surface proteins, such as Merozoite Surface Protein 1 (MSP-1) and Circumsporozoite Protein (CSP), which are essential for parasite survival, host cell invasion, and immune evasion [4, 8]. Because PfGWT1 is indispensable for the asexual blood stages of the parasite, it is considered a high-priority target for the development of new antimalarial therapies [6, 9]. Small molecule inhibitors like gepinacin and manogepix have shown potent activity against P. falciparum by disrupting this pathway [1, 12]. A primary challenge in targeting PfGWT1 is achieving sufficient selectivity to avoid inhibiting the human ortholog, PIG-W, which could lead to host toxicity [4, 10].

Other names

GWT1PfGWT1Inositol acyltransferasePFF0740cPf3D7_0625200GPI-anchored wall transfer protein 1, putative

Inhibition of inositol acyltransferase activity, which disrupts the biosynthesis of glycosylphosphatidylinositol (GPI) anchors and prevents the membrane attachment of essential parasite surface proteins.