The M17 leucyl metallopeptidases are metal-dependent hexameric enzymes that cleave N-terminal amino acids from peptide substrates. The M17 aminopeptidases from Plasmodium falciparum (Pf-M17) and Plasmodium vivax (Pv-M17) are postulated to liberate free amino acids from short haemoglobin peptides, for use in parasite protein production[1,2]. Inhibition of Pf-M17 results in parasite death both in vivo and in vitro[3,4,5], thereby validating Pf-M17 as a potential drug target for the design of new anti-malarial treatments. High sequence identity between Pf- and Pv- M17 aminopeptidases suggests Pv-M17 may also be an attractive drug target. To explore the potential for cross-species drug development, we produced recombinant Pf- and Pv-M17 and compared their structure and mechanisms of action. We investigated the relationship between oligomeric state and aminopeptidase activity, as well as the effect of metal ions on this relationship. We found both Pf and Pv- M17 exist in a metal-dependent dynamic equilibrium between an active hexamer and inactive smaller oligomers. Despite the high sequence identity between Pf- and Pv- M17, characterization of their activities in the presence of biologically relevant metal ions demonstrated unique activity profiles for each enzyme. During the Plasmodium life cycle the identity and concentration of metal ions fluctuates. Therefore, we propose parasites may be utilizing the M17 metal-dependent dynamic equilibrium as a biological regulator of haemoglobin proteolysis in parasites.