Departments of Pathology and Microbiology-Immunology, Northwestern University, Chicago, Illinois, USA.
Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA.
Trends Parasitol. 2014 Jul;30(7):350-60. doi: 10.1016/j.pt.2014.05.003. Epub 2014 Jun 19.
Fatty acylation--the addition of fatty acid moieties such as myristate and palmitate to proteins--is essential for the survival, growth, and infectivity of the trypanosomatids: Trypanosoma brucei, Trypanosoma cruzi, and Leishmania. Myristoylation and palmitoylation are critical for parasite growth, targeting and localization, and the intrinsic function of some proteins. The trypanosomatids possess a single N-myristoyltransferase (NMT) and multiple palmitoyl acyltransferases, and these enzymes and their protein targets are only now being characterized. Global inhibition of either process leads to cell death in trypanosomatids, and genetic ablation of NMT compromises virulence. Moreover, NMT inhibitors effectively cure T. brucei infection in rodents. Thus, protein acylation represents an attractive target for the development of new trypanocidal drugs.
脂肪酸酰化——向蛋白质中添加脂肪酸部分，如豆蔻酸和棕榈酸——对于锥虫的生存、生长和感染力至关重要：布氏锥虫、克氏锥虫和利什曼原虫。豆蔻酰化和棕榈酰化对于寄生虫的生长、靶向和定位以及一些蛋白质的固有功能至关重要。锥虫仅拥有一种 N-豆蔻酰转移酶（NMT）和多种棕榈酰酰基转移酶，这些酶及其蛋白靶标现在才被表征。这两种过程的全局抑制都会导致锥虫死亡，而 NMT 的遗传缺失会损害毒力。此外，NMT 抑制剂可有效治愈啮齿动物的布氏锥虫感染。因此，蛋白质酰化代表了开发新型杀锥虫药物的有吸引力的靶标。
