title: Uneven spread of cis- and trans-editing aminoacyl-tRNA synthetase domains within translational compartments of P. falciparum.
abstract: Accuracy of aminoacylation is dependent on maintaining fidelity during attachment of amino acids to cognate tRNAs. Cis- and trans-editing protein factors impose quality control during protein translation, and 8 of 36 Plasmodium falciparum aminoacyl-tRNA synthetase (aaRS) assemblies contain canonical putative editing modules. Based on expression and localization profiles of these 8 aaRSs, we propose an asymmetric distribution between the parasite cytoplasm and its apicoplast of putative editing-domain containing aaRSs. We also show that the single copy alanyl- and threonyl-tRNA synthetases are dually targeted to parasite cytoplasm and apicoplast. This bipolar presence of two unique synthetases presents opportunity for inhibitor targeting their aminoacylation and editing activities in twin parasite compartments. We used this approach to identify specific inhibitors against the alanyl- and threonyl-tRNA synthetases. Further development of such inhibitors may lead to anti-parasitics which simultaneously block protein translation in two key parasite organelles, a strategy of wider applicability for pathogen control.
authors.affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.
authors.forename: Sameena
authors.initials: S
authors.lastname: Khan
authors.forename: Arvind
authors.initials: A
authors.lastname: Sharma
authors.forename: Abhishek
authors.initials: A
authors.lastname: Jamwal
authors.forename: Vinay
authors.initials: V
authors.lastname: Sharma
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Pole
authors.forename: Kamal Kishor
authors.initials: KK
authors.lastname: Thakur
authors.forename: Amit
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry*; D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000201:enzymology; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D010963:Plasmodium falciparum / Q000201:enzymology*; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry*; D013914:Threonine-tRNA Ligase / Q000737:chemistry
chemical_list: D000977:Antiparasitic Agents; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins; D000604:Amino Acyl-tRNA Synthetases; D013914:Threonine-tRNA Ligase