Identification and characterisation of Toxoplasma gondii protein farnesyltransferase

Prenylated proteins are involved in the regulation of DNA replication and c ell cycling and have important roles in the regulation of cell proliferatio n. Protein farnesyltransferase and protein geranylgeranyltransferase are th e two enzymes responsible for catalysing isoprene lipid modifications. Rece ntly these enzymes have been targets for the development of cancer chemothe rapeutics. Using metabolic labelling we identified isoprenylated proteins w hich suggests the presence of protein farnesyltransferase in Toxoplasma gon dii. T gondii protein farnesyltransferase is heat-labile and requires Mg2and Zn2+ ions for full activity. Peptidomimetic analogues as well as short synthetic peptides were tested in vitro as possible competitors for farnesy ltransferase substrates. We found that the synthetic peptide (KTSCVIA) spec ifically inhibited T gondiiprotein farnesyltransferase but not mammalian (H eLa cells) farnesyltransferase. Therefore this study suggests the possible development of specific inhibitors of T gondiiprotein farnesyltransferase a s an approach to parasitic protozoa therapy. (C) 2001 Australian Society fo r Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.