Plasmodium falciparum protein farnesyltransferase (PfPFT)

Plasmodium falciparum protein farnesyltransferase (PfPFT) is a heterodimeric enzyme essential for the post-translational modification of proteins in the malaria parasite (UniProt, 2024). It catalyzes the attachment of a 15-carbon farnesyl isoprenoid group to the C-terminal cysteine of proteins containing a CaaX motif (PubMed, PMID: 11591741). This modification is crucial for the membrane anchoring and biological activity of various signaling proteins, including small GTPases like Ras and Rho homologs, which regulate parasite growth and differentiation (PubMed, PMID: 15608065). Because PfPFT is vital for the survival of the parasite during its erythrocytic stage, it has been identified as a promising target for antimalarial drug development (PubMed, PMID: 12692104). Inhibitors originally designed for human farnesyltransferase in cancer therapy, such as Tipifarnib and Lonafarnib, have shown potent activity against P. falciparum (PubMed, PMID: 15149171). However, achieving high selectivity over the human ortholog is critical to minimize host toxicity and side effects (PubMed, PMID: 15608065). The enzyme's unique structural features compared to the human version provide opportunities for the design of parasite-specific inhibitors (PubMed, PMID: 11591741). Ongoing research focuses on optimizing these compounds to overcome potential drug resistance and improve pharmacokinetic properties for clinical use (PubMed, PMID: 12692104).

Other names

Protein farnesyltransferaseFarnesyl-protein transferaseP. falciparum PFTPfFTProtein farnesyltransferase subunit alphaProtein farnesyltransferase subunit beta

Inhibition of the transfer of a farnesyl group from farnesyl pyrophosphate to the cysteine residue of a C-terminal CaaX motif on target proteins, preventing membrane localization and biological activity.