Author:
Gowri V S,Ghosh Indira,Sharma Amit,Madhubala Rentala
Abstract
AbstractBackgroundLeishmania 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 fromL. major.ResultsA total of 26 aminoacyl tRNA synthetases were identified using various computational and bioinformatics tools. Phylogenetic analysis and domain architectures of theL. majoraminoacyl tRNA synthetases suggest a probable archaeal/eukaryotic origin. Presence of additional domains or N- or C-terminal extensions in 11 aminoacyl tRNA synthetases fromL. majorsuggests possibilities such as additional tRNA binding or oligomerization or editing activity. Five freestanding editing domains were identified inL. major. Domain assignment revealed a novel asparagine tRNA synthetase paralog, asparagine synthetase A which has been so far reported from prokaryotes and archaea.ConclusionsA comprehensive bioinformatic analysis revealed 26 aminoacyl tRNA synthetases and five freestanding editing domains inL. 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.
Publisher
Springer Science and Business Media LLC
Cited by
40 articles.
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