Plasmodium falciparum acylguanidine 1 (PfACG1) (PfACG1)

Plasmodium falciparum acylguanidine 1 (PfACG1), also known as the aspartate-glutamate carrier isoform 1 (PF3D7_0910300), is a conserved protein in the malaria parasite that plays a critical role in mediating resistance to the preclinical antimalarial candidate MMV688533. Identified through whole-genome sequencing of drug-pressured parasite lines, PfACG1 is a member of the solute carrier family 25 (SLC25) and is implicated in essential cellular processes such as intracellular trafficking, lipid utilization, and endocytosis. While PfACG1 is not the primary direct target of the acylguanidine compound MMV688533, specific mutations in the protein, including G98V and W286R, confer low-grade resistance by potentially altering the parasite's metabolic or trafficking pathways. MMV688533 itself is a fast-acting antimalarial that shows high potency against multiple parasite stages and a high barrier to resistance, making it a promising candidate for single-dose malaria cures. PfACG1 is localized to distinct intracellular vesicles, and its characterization has provided valuable insights into the novel mode of action of acylguanidine-based therapeutics. Understanding the function of PfACG1 is essential for monitoring the emergence of resistance and for the further development of next-generation antimalarials targeting the parasite's transport and trafficking machinery.

Other names

PF3D7_0910300Aspartate-glutamate carrier isoform 1Acylguanidine 1PfAGC1

Resistance determinant; mutations in the protein confer reduced susceptibility to the antimalarial candidate MMV688533.