title: Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from Leishmania major.
abstract: 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.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: V S
authors.initials: VS
authors.lastname: Gowri
authors.forename: Indira
authors.initials: I
authors.lastname: Ghosh
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
authors.forename: Rentala
authors.initials: R
authors.lastname: Madhubala
mesh_terms: D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000145:classification / Q000235:genetics*; D019843:Archaeal Proteins / Q000235:genetics*; D001216:Asparagine / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics*; D019295:Computational Biology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D018320:Leishmania major / Q000201:enzymology / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D019843:Archaeal Proteins; D001426:Bacterial Proteins; D016207:Cytokines; D009363:Neoplasm Proteins; D015800:Protozoan Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D001216:Asparagine; D000604:Amino Acyl-tRNA Synthetases