Plasmodium falciparum M1-aminopeptidase: a promising target for the development of antimalarials

Abstract

Malaria is a devastating human parasitic disease that receives enhanced attention due to the emergence of resistance to traditional drugs. Thus, the search for new molecular targets is a major goal. PfAM1 is an aminopeptidase from Plasmodium falciparum, William H. Welch 1897, belonging to the M1 family of metalloproteases, which is a promising target of inhibitors to block the intra-erythrocytic stages of the parasite. Since its identification in 1998, many efforts have been done to validate PfAM1 as an appropriate target of antimalarials. The present work is a critical review of the main structural, functional and kinetic characteristics of PfAM1, as well as a summary of the effects of key inhibitors at molecular and cellular levels. The systematization of experimental results should contribute to a better understanding of the properties of PfAM1 as a target of antimalarials and promote research projects focused on the development of PfAM1 inhibitors.