Identity of a Plasmodium lactate/H+ symporter structurally unrelated to human transporters
Identity of a Plasmodium lactate/H+ symporter structurally unrelated to human transporters
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DOI：
10.1038/ncomms7284
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发表时间：
2015-02-01
影响因子：
16.6
通讯作者：
Beitz, Eric
中科院分区：
文献类型：
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作者：
Wu, Binghua;Rambow, Janis;Beitz, Eric
维持较高的糖酵解流率对于疟疾寄生虫的快速生长和毒力至关重要。寄生虫每摩尔葡萄糖释放两个摩尔乳酸作为厌氧最终产物。然而，疟原虫乳酸转运蛋白的分子特性尚不清楚。在这里，我们展示了微生物甲酸盐-亚硝酸盐转运体家族的一个成员，PfFNT，在恶性疟原虫中扮演着乳酸/质子转运体的角色。除L-乳酸外，PfFNT还转运生理上相关的D-乳酸、丙酮酸、醋酸盐和甲酸盐，并被抗疟原虫化合物根霉素衍生物、速尿和肉桂酸衍生物抑制，但不被对氯汞苯磺酸(PCMBS)抑制。我们关于PfFNT单羧酸盐转运的数据与用活寄生虫获得的数据一致。此外，PfFNT是原虫糖酵解途径的唯一转运体，其结构信息可从同源蛋白的晶体中获得，这使得它适合作为一种新的抗疟疾药物靶点进行进一步评估。
Maintenance of a high glycolytic flow rate is critical for the rapid growth and virulence of malarial parasites. The parasites release two moles of lactic acid per mole of glucose as the anaerobic end product. However, the molecular identity of the Plasmodium lactate transporter is unknown. Here we show that a member of the microbial formate-nitrite transporter family, PfFNT, acts as a lactate/proton symporter in Plasmodium falciparum. Besides L-lactate, PfFNT transports physiologically relevant D-lactate, as well as pyruvate, acetate and formate, and is inhibited by the antiplasmodial compounds phloretin, furosemide and cinnamate derivatives, but not by p-chloromercuribenzene sulfonate (pCMBS). Our data on PfFNT monocarboxylate transport are consistent with those obtained with living parasites. Moreover, PfFNT is the only transporter of the plasmodial glycolytic pathway for which structure information is available from crystals of homologous proteins, rendering it amenable to further evaluation as a novel antimalarial drug target.