The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin
The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin
复制标题
DOI：
10.1074/jbc.273.26.16192
复制
发表时间：
1998-06-26
影响因子：
4.8
通讯作者：
Meshnick, SR
中科院分区：
文献类型：
--
作者：
Bhisutthibhan, J;Pan, XQ;Meshnick, SR
青蒿素及其衍生物是重要的抗疟疾新药。当被恶性疟原虫感染的红细胞与[10-H-3]双氢青蒿素孵育时，几种疟疾特异性蛋白被标记。这些蛋白质之一是恶性疟原虫翻译控制的肿瘤蛋白(TCTP)同源物。在体外，双氢青蒿素在氯化高铁血红素存在下与重组TCTP发生共价反应。药物和蛋白质之间的联系随着药物浓度的增加而增加，稳定在大约1个药物/TCTP分子。经Scatchard分析，TCTP上有2个氯化血红素结合部位，其解离常数接近18微米，用碘乙酰胺阻断单半胱氨酸部分时，氯化血红素结合不受影响，而药物结合减少三分之二。因此，在氯化血红素存在的情况下，TCTP在体内和体外与青蒿素反应，并似乎与氯化高铁血红素结合，疟疾TCTP的功能以及这种反应在青蒿素作用机制中的作用有待阐明。
Artemisinin and its derivatives are important new antimalarial drugs. When Plasmodium falciparum-infected erythrocytes are incubated with [10-H-3]dihydroartemisinin, several malaria-specific proteins become labeled. One of these proteins is the P. falciparum translationally controlled tumor protein (TCTP) homolog. In vitro, dihydroartemisinin reacts covalently with recombinant TCTP in the presence of hemin. The association between drug and protein increases with increasing drug concentration, plateauing at approximately 1 drug/TCTP molecule. By Scatchard analysis, there appear to be 2 hemin binding sites on TCTP with dissociation constants of similar to 18 mu M, When the single cysteine moiety is blocked by pretreatment with iodoacetamide, hemin binding is not affected, whereas drug binding is reduced by two-thirds. Thus, TCTP reacts with artemisinin in situ and in vitro in the presence of hemin and appears to bind to hemin, The function of the malarial TCTP and the role of this reaction in the mechanism of action of artemisinin await elucidation.