A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum.
A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum.
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DOI：
10.1186/1471-2164-10-644
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发表时间：
2009-12-31
期刊：
影响因子：
4.4
通讯作者：
Sharma A
中科院分区：
文献类型：
--
作者：
Bhatt TK;Kapil C;Khan S;Jairajpuri MA;Sharma V;Santoni D;Silvestrini F;Pizzi E;Sharma A
疟原虫是疟疾的病原体，每年影响5亿人，夺走约200万人的生命。疟原虫基因组测序的完成和数据库的建立，为寄生虫基因组的系统研究提供了平台。氨基酰基-tRNA合成酶(AARs)是蛋白质翻译和其他重要细胞过程的关键酶。我们报告了对恶性疟原虫基因组的广泛分析，以鉴定和分类这种生物中的AARS。利用各种计算和生物信息学工具，我们在恶性疟原虫中鉴定了37个AARs。我们的主要观察结果是：(I)与许多其他生物相比，恶性疟原虫中专用于AARs的蛋白质组分非常高；(Ii)37个Pf-AARs序列中有23个含有信号肽，可能将它们定向到不同的细胞器；(Iii)Pf-AARs的表达谱在寄生虫的不同生活史阶段有很大差异；(Iv)几个PfaaRSs具有非常不寻常的结构域结构；(V)系统发育分析揭示了几种寄生虫AARs与细菌和植物AARs的进化关系；(Vi)三维结构建模提供了可用于发现针对寄生虫AARs的抑制剂的见解。根据我们的生物信息学分析，我们已经鉴定了37个PF-AARs。我们的数据揭示了这个蛋白质家族的几个独特属性。我们已经根据预测的定位、系统发育、结构域结构及其整体蛋白质表达谱对所有37个PF-AARS进行了注释。这项工作中阐述的一组不同的特征将为实验剖析这一酶家族提供一个平台，可能为发现治疗疟疾的新药提供平台。
Plasmodium parasites are causative agents of malaria which affects >500 million people and claims ~2 million lives annually. The completion of Plasmodium genome sequencing and availability of PlasmoDB database has provided a platform for systematic study of parasite genome. Aminoacyl-tRNA synthetases (aaRSs) are pivotal enzymes for protein translation and other vital cellular processes. We report an extensive analysis of the Plasmodium falciparum genome to identify and classify aaRSs in this organism. Using various computational and bioinformatics tools, we have identified 37 aaRSs in P. falciparum. Our key observations are: (i) fraction of proteome dedicated to aaRSs in P. falciparum is very high compared to many other organisms; (ii) 23 out of 37 Pf-aaRS sequences contain signal peptides possibly directing them to different cellular organelles; (iii) expression profiles of Pf-aaRSs vary considerably at various life cycle stages of the parasite; (iv) several PfaaRSs posses very unusual domain architectures; (v) phylogenetic analyses reveal evolutionary relatedness of several parasite aaRSs to bacterial and plants aaRSs; (vi) three dimensional structural modelling has provided insights which could be exploited in inhibitor discovery against parasite aaRSs. We have identified 37 Pf-aaRSs based on our bioinformatics analysis. Our data reveal several unique attributes in this protein family. We have annotated all 37 Pf-aaRSs based on predicted localization, phylogenetics, domain architectures and their overall protein expression profiles. The sets of distinct features elaborated in this work will provide a platform for experimental dissection of this family of enzymes, possibly for the discovery of novel drugs against malaria.
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