Cloning and characterization of a vacuolar ATPase A subunit homologue from Plasmodium falciparum

Abstract

The distribution of the antimalarial drug chloroquine is determined to a significant extent by a transvacuolar pH gradient in Plasmodium falciparum. A proton pump similar to the vacuolar ATPase found in many cell types has been suggested to maintain a pH gradient across the membranes of acidic compartments in the parasite. In order to understand and define the components involved in the mechanism of acidification of parasite vesicles, we have cloned and characterized a gene, designated VAP-A, encoding a P. falciparum homologue of the catalytic A subunit of the vacuolar ATPase. The VAP-A gene encodes a polypeptide of 611 amino acids which shows between 56 to 61% amino acid identity over its e..