Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite
Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite
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DOI：
10.1101/gr.913403
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发表时间：
2003-04-01
期刊：
影响因子：
7
通讯作者：
Wang, YF
中科院分区：
文献类型：
--
作者：
Wu, YM;Wang, XY;Wang, YF
由于恶性疟原虫寄生虫对现有药物的耐药性日益增强，寻找新的抗疟药物靶标迫在眉睫。蛋白酶在寄生虫感染和发育过程中，特别是在宿主红细胞破裂/侵入和血红蛋白降解过程中起着不可或缺的作用，因此是有吸引力的抗疟靶点。然而，到目前为止，只有少数的蛋白酶已被确定和特点的疟原虫物种。使用广泛的序列相似性搜索，我们已经确定了恶性疟原虫基因组中的92个推定的蛋白酶。一组推定的蛋白酶，包括钙蛋白酶，后半胱天冬酶，和信号肽酶I已被牵连到的基本寄生虫活动的中央介质，并与脊椎动物宿主远亲。此外，基于微阵列和RT-PCR结果以及公开可用的微阵列和蛋白质组学数据，在92个中，至少88个已被证明在转录水平编码基因产物。本研究代表了一个初步的努力，以确定一组表达，活性和必需的蛋白酶作为目标的基于通道的药物设计。
The search for novel antimalarial drug targets is urgent due to the growing resistance of Plasmodium falciparum parasites to available drugs. Proteases are attractive antimalarial targets because of their indispensable roles in parasite infection and development, especially in the processes of host erythrocyte rupture/invasion and hemoglobin degradation. However, to date, only a small number of proteases have been identified and characterized in-Plasmodium species. Using an extensive sequence similarity search, we have identified 92 putative proteases in the P. falciparum genome. A set of putative proteases including calpain, metacaspase, and signal peptidase I have been implicated to be central mediators for essential parasitic activity and distantly related to the vertebrate host. Moreover, of the 92, at least 88 have been demonstrated to code for gene products at the transcriptional levels, based upon the microarray and RT-PCR results, and the publicly available microarray and proteomics data. The present study represents an initial effort to identify a set of expressed, active, and essential proteases as targets for inhibitor-based drug design.