Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from Leishmania major
Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from Leishmania major
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DOI：
10.1186/1471-2164-13-621
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发表时间：
2012-11-14
期刊：
影响因子：
4.4
通讯作者：
Madhubala, Rentala
中科院分区：
文献类型：
--
作者：
Gowri, V. S.;Ghosh, Indira;Madhubala, Rentala
背景：大利什曼原虫是一种原虫，是皮肤利什曼病的病原体。由于目前可用的抗利什曼药物的耐药性的发展，对特定的抑制剂和新的药物靶点的需求日益增长。在这方面，氨酰tRNA合成酶，蛋白质合成的关键，最近在动态体研究界受到了关注。这是首次对主要乳杆菌的氨酰基tRNA合成酶及其类似物和其他相关蛋白质进行了全面的调查。结果：利用各种计算和生物信息学工具，共鉴定出26种氨基酰基tRNA合成酶。主要氨基酰tRNA合成酶的系统发育分析和结构域结构表明，它可能起源于古细菌/真核生物。大链霉菌的11个氨基酰基tRNA合成酶中存在额外的结构域或N-端或C-端延伸，这表明可能存在额外的tRNA结合或寡聚或编辑活性。在L.Major中确定了五个独立的编辑域。结构域分配揭示了一个新的天冬酰胺tRNA合成酶Paralog，即天冬酰胺合成酶A，这是目前在原核生物和考古生物中报道的一个新的天冬酰胺tRNA合成酶A。结论：通过全面的生物信息学分析，发现了26个氨基酰基tRNA合成酶和5个独立的编辑结构域。鉴定了两个与人EMAP II相似的EMAP(内皮单核细胞激活多肽)II样蛋白，表明它们参与了多合成酶复合体的形成。虽然tRNA合成酶的系统发育表明可能是古生物/真核生物的起源，但天冬酰胺合成酶A的系统发育强烈表明细菌的起源。这项工作中确定的独特特征为设计针对寄生虫氨基酰tRNA合成酶及其类似物的抑制剂提供了理论基础。
Background: Leishmania major, a protozoan parasite, is the causative agent of cutaneous leishmaniasis. Due to the development of resistance against the currently available anti-leishmanial drugs, there is a growing need for specific inhibitors and novel drug targets. In this regards, aminoacyl tRNA synthetases, the linchpins of protein synthesis, have received recent attention among the kinetoplastid research community. This is the first comprehensive survey of the aminoacyl tRNA synthetases, their paralogs and other associated proteins from L. major.Results: A total of 26 aminoacyl tRNA synthetases were identified using various computational and bioinformatics tools. Phylogenetic analysis and domain architectures of the L. major aminoacyl tRNA synthetases suggest a probable archaeal/eukaryotic origin. Presence of additional domains or N- or C-terminal extensions in 11 aminoacyl tRNA synthetases from L. major suggests possibilities such as additional tRNA binding or oligomerization or editing activity. Five freestanding editing domains were identified in L. major. Domain assignment revealed a novel asparagine tRNA synthetase paralog, asparagine synthetase A which has been so far reported from prokaryotes and archaea.Conclusions: A comprehensive bioinformatic analysis revealed 26 aminoacyl tRNA synthetases and five freestanding editing domains in L. major. Identification of two EMAP (endothelial monocyte-activating polypeptide) II-like proteins similar to human EMAP II-like proteins suggests their participation in multisynthetase complex formation. While the phylogeny of tRNA synthetases suggests a probable archaeal/eukaryotic origin, phylogeny of asparagine synthetase A strongly suggests a bacterial origin. The unique features identified in this work provide rationale for designing inhibitors against parasite aminoacyl tRNA synthetases and their paralogs.