期刊
INTERNATIONAL JOURNAL FOR PARASITOLOGY
卷 31, 期 13, 页码 1489-1497出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0020-7519(01)00268-5
关键词
protein prenylation; protein farnesyltransferase; Toxoplasma gondii; tachyzoite
类别
Prenylated proteins are involved in the regulation of DNA replication and cell cycling and have important roles in the regulation of cell proliferation. Protein farnesyltransferase and protein geranylgeranyltransferase are the two enzymes responsible for catalysing isoprene lipid modifications. Recently these enzymes have been targets for the development of cancer chemotherapeutics. Using metabolic labelling we identified isoprenylated proteins which suggests the presence of protein farnesyltransferase in Toxoplasma gondii. T gondii protein farnesyltransferase is heat-labile and requires Mg2+ and Zn2+ ions for full activity. Peptidomimetic analogues as well as short synthetic peptides were tested in vitro as possible competitors for farnesyltransferase substrates. We found that the synthetic peptide (KTSCVIA) specifically inhibited T gondiiprotein farnesyltransferase but not mammalian (HeLa cells) farnesyltransferase. Therefore this study suggests the possible development of specific inhibitors of T gondiiprotein farnesyltransferase as an approach to parasitic protozoa therapy. (C) 2001 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.
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