单个氨基酸残基可决定肌浆网钙ATP酶对青蒿素的敏感性。
A single amino acid residue can determine the sensitivity of SERCAs to artemisinins.
作者信息
Uhlemann Anne-Catrin, Cameron Angus, Eckstein-Ludwig Ursula, Fischbarg Jorge, Iserovich Pavel, Zuniga Felipe A, East Malcolm, Lee Anthony, Brady Leo, Haynes Richard K, Krishna Sanjeev
机构信息
Department of Cellular and Molecular Medicine, Infectious Diseases, St. George's Hospital Medical School, London SW17 0RE, UK.
出版信息
Nat Struct Mol Biol. 2005 Jul;12(7):628-9. doi: 10.1038/nsmb947. Epub 2005 Jun 5.
Artemisinins are the most important class of antimalarial drugs. They specifically inhibit PfATP6, a SERCA-type ATPase of Plasmodium falciparum. Here we show that a single amino acid in transmembrane segment 3 of SERCAs can determine susceptibility to artemisinin. An L263E replacement of a malarial by a mammalian residue abolishes inhibition by artemisinins. Introducing residues found in other Plasmodium spp. also modulates artemisinin sensitivity, suggesting that artemisinins interact with the thapsigargin-binding cleft of susceptible SERCAs.
青蒿素是最重要的一类抗疟药物。它们特异性抑制PfATP6，这是恶性疟原虫的一种SERCA型ATP酶。在此我们表明，SERCA跨膜片段3中的单个氨基酸可决定对青蒿素的敏感性。将疟原虫的一个氨基酸L263替换为哺乳动物的氨基酸会消除青蒿素的抑制作用。引入其他疟原虫物种中发现的氨基酸也会调节青蒿素敏感性，这表明青蒿素与敏感SERCA的毒胡萝卜素结合裂隙相互作用。
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