Working in concert: the metalloaminopeptidases from Plasmodium falciparum

Malaria remains the world s most prevalent human parasitic disease. Because of the rapid spread of drug resistance in parasites, there is an urgent need to identify diverse new drug targets. One group of proteases that are emerging as targets for novel antimalarials are the metalloaminopeptidases. These enzymes catalyze the removal of the N-terminal amino acids from proteins and peptides. Given the restricted specificities of each of these enzymes for different N-terminal amino acids, it is thought that they act in concert to facilitate protein turnover. Here we review recent structure and functional data relating to the development of the Plasmodium falciparum metalloaminopeptidases as drug targets.