Identification and characterization of novel Plasmodium falciparum cyclophilins and their roles in the antimalarial actions of cyclosporin A and derivatives

Abstract

Cyclophilins are distributed widely among different organisms and are proposed drug targets for a number of diseases including HIV and hepatitis C infection and ischemia. Cyclophilins play roles in folding and chaperoning of cellular proteins and are the major receptors for the immunosuppressive drug cyclosporin A (CsA). CsA and certain non-immunosuppressive derivatives (e.g., valspodar) possess potent antimalarial activity. We are interested in the role (if any) played by cyclophilins in parasite killing by cyclosporins. We, and others, have previously characterized two CsA-binding cyclophilins (PfCYP19A and PfCYP19B) but a family of genes encoding uncharacterized cyclophilins/cyclophilin-like proteins is also seen in the P. falciparum genome (Figure 1).