Capturing structural details of biological macromolecules in the native state is the focal interest of cryoelectron microscopy and tomography-based methods. Structures of recombinant protein complexes generated in heterologous expression systems may broadly agree with the native conformations, however the latter may still retain crucial nuances that guide functionality within the cellular milieu. We have utilized a “computational purification” approach to resolve the structures of two enzyme complexes present in a highly heterogeneous sample extracted from the blood stage of the malarial parasite Plasmodium falciparum. The native structures of the metallo-aminopeptidases PfA-M17 (hexamer) and PfM18AAP (dodecamer) were solved by single particle reconstruction at resolutions between 2.75 Å - 3.4 Å. Both enzyme complexes are required for haemoglobin metabolism by the parasite, and are therefore key druggable targets in anti-malarial therapeutic development. Our native structures show clear density for the regulatory loops, hitherto partially or entirely unresolved in crystal structures of recombinantly generated enzymes, controlling access to the active sites in both cases. The structure of the hexameric PfA-M17 resolved without symmetry imposition shows variable conformation of the regulatory loop in the protomers, establishing unsynchronized substrate processing within the complex. All atom simulation of the native cryoEM structures clearly demonstrate an efficient, dynamic gating model for active site access modulated by loop movement. These maps further provide structural details of metal (Zn2+, Mn2+) and anion coordination (CO3-, SO42-), as well as that of protomer interfacial contacts in the native state of the enzyme complexes. The knowledge of physiological ion coordination and protomeric contacts, as well as complete structural understanding, for the first time, of loop-gated substrate access regulation, are key features for development of efficient inhibitors against these crucial enzymes from P. falciparum.