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Potent Inhibitor of N-Myristoylation

A Novel Molecular Target For Cancer

¹ Department of Pathology and Saskatoon Cancer Center, College of Medicine
² College of Pharmacy and Nutrition, University of Saskatchewan,
³ Plant Biotechnology Institute, National Research Council of Canada, Saskatoon, Saskatchewan, Canada

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the cotranslational and/or posttranslational transfer of myristate to the NH₂ terminus of the glycine residue of a number of important proteins that have diverse biological functions and thus have been proposed as potential targets for chemotherapeutic drug design. Earlier, we demonstrated that NMT is more active in colonic epithelial neoplasms than in corresponding normal-appearing colonic tissue. Furthermore, an increased expression of NMT was also observed in gallbladder carcinoma. In the present study, we report a novel protein inhibitor of NMT. This protein caused a potent concentration-dependent inhibition of human NMT with half-maximal inhibition at 4.5 ± 0.35 nM. This study will serve as a template for further investigations in the area of protein myristoylation.