M17 leucyl aminopeptidases are metal-dependent hexameric enzymes found in almost all kingdoms of life with a diverse range of functions. A major function of M17 aminopeptidases is the cleavage of single amino acids from peptide substrates. The M17 aminopeptidases from malaria-causing parasites, 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]. Pf-M17 has been validated as a potential drug target for the design of new anti-malarial treatments, and high sequence identity between Pf- and Pv-M17 suggest Pv-M17 may also present as an attractive target[3,4]. To further characterise these aminopeptidases, we produced recombinant Pf- and Pv-M17 and investigated the relationship between oligomeric state and aminopeptidase activity, and the role metal ions play in these different molecular mechanisms. We found both Pf- and Pv-M17 exist in a metal-dependent equilibrium between an active hexamer and inactive small oligomers. Hexamerisation into the active state is mediated by metal ion identity and concentration and when metal binding is disrupted, oligomerization and subsequent activity are compromised. The novel X-ray crystal structure of Pv-M17, in combination with ongoing Cryo-electron microscopy and SAXS studies will provide insight into structural differences of the various Pf- and Pv-M17 oligomeric states. During the Plasmodium life cycle the identity and concentration of metal ions fluctuates[5], therefore we propose parasites may be utilizing a metal-dependent dynamic equilibrium as a biological regulator of M17 protease activity.