Malaria continues to be a significant cause of death and morbidity worldwide, and there is a need for new antimalarial drugs with novel targets. We have focused as a potential target for drug development on N-myristoyl transferase (NMT), an enzyme that acylates a wide range of substrate proteins. The NMT substrates in Plasmodium falciparum include some proteins that are common to processes in eukaryotes such as secretory transport and others that are unique to apicomplexan parasites. Myristoylation facilitates a protein interaction with membranes that may be strengthened by further lipidation, and the inhibition of NMT results in incorrect protein localization and the consequent disruption of function. The diverse roles of NMT substrates mean that NMT inhibition has a pleiotropic and severe impact on parasite development, growth, and multiplication. To study the mode of action underlying NMT inhibition, it is important to consider the function of proteins upstream and downstream of NMT. In this work, we therefore present our current perspective on the different functions of known NMT substrates as well as compare the inhibition of cotranslational myristoylation to the inhibition of known targets upstream of NMT.

中文翻译：

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N-肉豆蔻酰化作为疟疾中的药物靶标：探索N-肉豆蔻酰转移酶底物在抑制剂作用方式中的作用

疟疾仍然是全世界范围内死亡和发病的重要原因，因此需要具有新靶标的新型抗疟药。我们已将N-肉豆蔻酰基转移酶（NMT）（一种可将多种底物蛋白酰化的酶）作为药物开发的潜在目标。恶性疟原虫中的NMT底物包括一些真核生物过程中常见的蛋白，例如分泌转运蛋白，以及其他一些复合体寄生虫所特有的蛋白。肉豆蔻酰基化促进了蛋白质与膜的相互作用，该相互作用可通过进一步的脂化作用而加强，NMT的抑制导致错误的蛋白质定位和随后的功能破坏。NMT底物的不同作用意味着NMT抑制对寄生虫的发育，生长和繁殖具有多效性和严重影响。要研究NMT抑制作用的作用方式，重要的是要考虑NMT上游和下游蛋白的功能。在这项工作中，