Structural, kinetic and biophysical characterization of the Plasmodium M1 and M17 aminopeptidases

This thesis describes the structural, kinetic and biophysical characterization of the M1 and M17 enzymes from the two leading causes of malaria in humans, Plasmodium falciparum and Plasmodium vivax, and the murine model species, Plasmodium berghei. We discovered a novel mechanism of M17 enzyme regulation through manipulation of the active conformation, profiled the extended substrate specificity fingerprints of the Plasmodium M1 and M17 enzymes, and demonstrated the ability of small inhibitory molecules to achieve cross-species and dual-enzyme potency. As Plasmodium M1 and M17 enzymes are validated targets for new anti-malarials, this work will assist in designing effective novel therapeutics.