Shrivastav Anuraag, Pasha Mohammed K, Selvakumar Ponniah, Gowda Sweta, Olson Douglas J H, Ross Andrew R S, Dimmock Jonathan R, Sharma Rajendra K
Department of Pathology and Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, 20 Campus Drive, Saskatoon, Saskatchewan S7N 4H4, Canada.
Cancer Res. 2003 Nov 15;63(22):7975-8.
N-myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the cotranslational and/or posttranslational transfer of myristate to the NH(2) 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.
N-肉豆蔻酰转移酶（NMT）是一种必需的真核酶，它催化肉豆蔻酸共翻译和/或翻译后转移到许多具有不同生物学功能的重要蛋白质的甘氨酸残基的NH₂末端，因此被提议作为化疗药物设计的潜在靶点。此前，我们证明NMT在结肠上皮肿瘤中比在相应外观正常的结肠组织中更具活性。此外，在胆囊癌中也观察到NMT表达增加。在本研究中，我们报告了一种新型的NMT蛋白抑制剂。这种蛋白对人NMT产生了强大的浓度依赖性抑制作用，半数最大抑制浓度为4.5±0.35 nM。本研究将为蛋白质肉豆蔻酰化领域的进一步研究提供模板。
