Peptidyl-prolyl cis-trans isomerase 1 (PfCyp19) (PfCyp19)

Plasmodium falciparum cyclophilin 19 (PfCyp19) is a 19 kDa protein belonging to the immunophilin family, characterized by its peptidyl-prolyl cis-trans isomerase (PPIase) activity (UniProt: Q8I4V8). It functions as a molecular chaperone, facilitating the proper folding and trafficking of proteins essential for the survival and replication of the malaria parasite during its erythrocytic stage (PMID: 12832018). PfCyp19 is the primary intracellular receptor for the drug Cyclosporin A (CsA) within the parasite; the resulting CsA-PfCyp19 complex is thought to inhibit vital parasite processes, although the exact downstream targets differ from the human calcineurin pathway (PMID: 21613407). Because of its high expression and critical role in parasite viability, PfCyp19 is considered a promising target for novel antimalarial therapies, particularly those using non-immunosuppressive cyclophilin inhibitors like Alisporivir (PMID: 25691595). Targeting this enzyme offers a potential strategy to overcome resistance to conventional antimalarial drugs by disrupting protein homeostasis. The structural differences between PfCyp19 and human cyclophilins are currently being explored to develop parasite-specific inhibitors that minimize host toxicity (PMID: 17010160).

Other names

Cyclophilin 19PfCyP19Peptidyl-prolyl cis-trans isomerase 1PPIase 1Plasmodium falciparum cyclophilin A-like protein

Inhibition of peptidyl-prolyl cis-trans isomerase activity, leading to protein misfolding and disruption of essential parasite biological processes.