Crystal structure of phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with amodiaquine
Crystal structure of phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with amodiaquine
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DOI：
10.1016/j.bmcl.2012.06.032
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发表时间：
2012-08-01
影响因子：
2.7
通讯作者：
Jez, Joseph M.
中科院分区：
文献类型：
--
作者：
Lee, Soon Goo;Alpert, Tara D.;Jez, Joseph M.
磷酸乙醇胺N-甲基转移酶（PMT）是恶性疟原虫磷脂合成的关键酶。PfPMT催化磷酸乙醇胺的三甲基化以产生磷酸胆碱，然后用于磷脂酰胆碱合成。在这里，我们描述了2.0 A分辨率的X-射线晶体结构的PfPMT与阿莫地喹复杂。为了更好地表征阿莫地喹对PfPMT的抑制作用，我们使用直接放射化学测定法测定了一系列氨基喹啉的IC 50值。结构和功能分析为开发新型PfPMT小分子抑制剂提供了可能的途径。(c)2012爱思唯尔有限公司保留所有权利。
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 2.0 A resolution X-ray crystal structure of PfPMT in complex with amodiaquine. To better characterize inhibition of PfPMT by amodiaquine, we determined the IC50 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. (c) 2012 Elsevier Ltd. All rights reserved.