Department of Biology, Washington University in St. Louis, One Brookings Drive, Campus Box 1137, St. Louis, MO 63130, USA.
Department of Biology, Washington University in St. Louis, One Brookings Drive, Campus Box 1137, St. Louis, MO 63130, USA.
Trends Parasitol. 2014 May;30(5):241-50. doi: 10.1016/j.pt.2014.03.001. Epub 2014 Mar 28.
Parasitic nematodes that infect humans, animals, and plants cause health problems, livestock and agricultural losses, and economic damage worldwide and are important targets for drug development. The growing availability of nematode genomes supports the discovery of new pathways that differ from host organisms and are a starting point for structural and functional studies of novel antiparasitic targets. As an example of how genome data, structural biology, and biochemistry integrate into a research cycle targeting parasites, we summarize the discovery of the phosphobase methylation pathway for phospholipid synthesis in nematodes and compare the phosphoethanolamine methyltransferases (PMTs) from nematodes, plants, and Plasmodium. Crystallographic and biochemical studies of the PMTs in this pathway provide a foundation that guides the next steps that close the genome-structure-function circle.
寄生在人类、动物和植物体内的线虫会导致健康问题、牲畜和农业损失以及全球经济损失，它们是药物开发的重要目标。线虫基因组的可用性不断增加，为发现与宿主生物不同的新途径提供了支持，这些途径是研究新型抗寄生虫靶标的结构和功能的起点。作为基因组数据、结构生物学和生物化学如何整合到针对寄生虫的研究周期的一个例子，我们总结了线虫磷脂合成中磷酸碱基甲基化途径的发现，并比较了线虫、植物和疟原虫中的磷酸乙醇胺甲基转移酶（PMTs）。该途径中 PMTs 的晶体学和生化研究为指导下一步缩小基因组-结构-功能循环提供了基础。
