Department of Biology, Washington University, St. Louis, MO 63130, USA.
Bioorg Med Chem Lett. 2012 Aug 1;22(15):4990-3. doi: 10.1016/j.bmcl.2012.06.032. Epub 2012 Jun 17.
Phosphoethanolamine N-methyltransferase (PMT) is essential for phospholipid biogenesis in the malarial parasite Plasmodium falciparum. PfPMT catalyzes the triple methylation of phosphoethanolamine to produce phosphocholine, which is then used for phosphatidylcholine synthesis. Here we describe the 2.0Å resolution X-ray crystal structure of PfPMT in complex with amodiaquine. To better characterize inhibition of PfPMT by amodiaquine, we determined the IC(50) values of a series of aminoquinolines using a direct radiochemical assay. Both structural and functional analyses provide a possible approach for the development of new small molecule inhibitors of PfPMT.
磷酸乙醇胺 N-甲基转移酶（PMT）是疟原虫 Plasmodium falciparum 中磷脂生物合成所必需的。PfPMT 催化磷酸乙醇胺的三重甲基化生成磷酸胆碱，然后用于磷脂酰胆碱的合成。在这里，我们描述了 PfPMT 与阿莫地喹复合物的 2.0Å 分辨率 X 射线晶体结构。为了更好地描述阿莫地喹对 PfPMT 的抑制作用，我们使用直接放射性化学测定法测定了一系列氨基喹啉的 IC50 值。结构和功能分析为开发 PfPMT 的新型小分子抑制剂提供了一种可能的方法。
