Partial characterization of a cysteine protease inhibitor of Plasmodium vivax

Abstract

Cysteine proteases play key roles in the biology of Plasmodium parasites and are recognized as antimalarial drug targets. Because these enzymes are involved in diverse biological functions, precise regulation is required to prevent unnecessary damage to both parasites and hosts. In this study, we identified an endogenous inhibitor of cysteine protease of Plasmodium vivax (PvICP) and characterized its biochemical properties. PvICP was found to share highly similar structural characteristics with orthologous proteins from other Plasmodium species. Recombinant PvICP (rPvICP) expressed in Escherichia coli showed a broad range of inhibitory activity against falcipain family cysteine proteases, including vivapain-3, vivapain-4, falcipain-3, malapain-2, and malapain-4, with more potent inhibitory activity against vivapain-3 and vivapain-4. rPvICP’s inhibitory activity was not significantly affected by pH, suggesting its broad biological functions. These findings provide new insights into PvICP and lay the groundwork for future studies exploring its biological significance and potential as a therapeutic target in malaria research.