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恶性疟原虫水甘油通道蛋白基因的有限遗传多样性。

Limited genetic diversity of the Plasmodium falciparum aquaglyceroporin gene.

作者信息

Bahamontes-Rosa Noemí, Wu Binghua, Beitz Eric, Kremsner Peter G, Kun Jürgen F J

机构信息

University of Tübingen, Department of Parasitology, Tübingen, Germany.

出版信息

Mol Biochem Parasitol. 2007 Dec;156(2):255-7. doi: 10.1016/j.molbiopara.2007.08.001. Epub 2007 Aug 7.

Abstract

In Plasmodium falciparum small solutes like water, ammonium, glycerol and others are transported by a parasite-encoded channel into the parasite. The gene encoding this channel is termed P. falciparum aquaglyceroporin (PfAQP) and is a single-copy gene and highly homologous to other aquaporins from other protozoa. Aquaporins are considered to be attractive targets for drug treatment and more so since the human and parasite aquaporins show considerable sequence differences. To investigate whether PfAQP may be suitable as a conserved target for potential aquaporin blocking agents we determined the DNA sequences of PfAQP from 65 parasite strains, either from in vitro cultured laboratory strains or from parasites obtained in an malaria-endemic region of Gabon. Only two non-synonymous mutations were found and functionally tested by a methylamine efflux assay. The efflux activity of all variants tested was similar. The lack of functionally variability suggests an invariable protein core, which may restrict parasite populations from evading therapeutic pressure if PfAQP inhibitors will be found.

摘要

在恶性疟原虫中,水、铵、甘油等小分子溶质通过一种由寄生虫编码的通道转运进入寄生虫体内。编码该通道的基因被称为恶性疟原虫水甘油通道蛋白(PfAQP),它是一个单拷贝基因,与其他原生动物的水通道蛋白高度同源。水通道蛋白被认为是药物治疗的有吸引力的靶点,尤其是因为人类和寄生虫的水通道蛋白显示出相当大的序列差异。为了研究PfAQP是否可能作为潜在水通道蛋白阻断剂的保守靶点,我们测定了来自65个寄生虫菌株的PfAQP的DNA序列,这些菌株要么来自体外培养的实验室菌株,要么来自加蓬疟疾流行地区获得的寄生虫。仅发现两个非同义突变,并通过甲胺外流试验进行了功能测试。所有测试变体的外流活性相似。缺乏功能变异性表明存在一个不变的蛋白质核心,如果发现PfAQP抑制剂,这可能会限制寄生虫群体逃避治疗压力。

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