Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
BMC Genomics. 2009 Dec 31;10:644. doi: 10.1186/1471-2164-10-644.
Plasmodium parasites are causative agents of malaria which affects >500 million people and claims approximately 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.
疟原虫是疟疾的病原体，每年影响超过 5 亿人，导致约 200 万人死亡。疟原虫基因组测序的完成和 PlasmoDB 数据库的可用性为寄生虫基因组的系统研究提供了一个平台。氨酰-tRNA 合成酶（aaRSs）是蛋白质翻译和其他重要细胞过程的关键酶。我们报告了对疟原虫 falciparum 基因组的广泛分析，以鉴定和分类该生物体中的 aaRSs。
使用各种计算和生物信息学工具，我们在 P. falciparum 中鉴定出 37 种 aaRSs。我们的主要观察结果是：（i）与许多其他生物体相比，P. falciparum 中专门用于 aaRSs 的蛋白质组分数非常高；（ii）37 个 Pf-aaRS 序列中有 23 个序列包含可能将它们引导到不同细胞细胞器的信号肽；（iii）寄生虫不同生命周期阶段 Pf-aaRSs 的表达谱差异很大；（iv）几个 PfaaRSs 具有非常不寻常的结构域架构；（v）系统发育分析显示，几种寄生虫 aaRSs 与细菌和植物 aaRSs 具有进化关系；（vi）三维结构建模提供了可以在寄生虫 aaRSs 抑制剂发现中利用的见解。
我们根据我们的生物信息学分析鉴定了 37 种 Pf-aaRSs。我们的数据揭示了该蛋白质家族的几个独特属性。我们根据预测的定位、系统发育、结构域架构及其整体蛋白质表达谱对所有 37 种 Pf-aaRSs 进行了注释。本文中详细阐述的一系列独特特征将为该酶家族的实验剖析提供一个平台，可能为发现抗疟疾的新型药物提供帮助。
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