A nondiscriminating glutamyl-tRNA synthetase in the plasmodium apicoplast: The first enzyme in an indirect aminoacylation pathway

Boniface M. Mailu, Gowthaman Ramasamay, Devaraja G. Mudeppa, Ling Li, Scott E. Lindner, Megan J. Peterson, Amy E. DeRocher, Stefan H.I. Kappe, Pradipsinh K. Rathod, Malcolm J. Gardner

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The malaria parasite Plasmodium falciparum and related organisms possess a relict plastid known as the apicoplast. Apicoplast protein synthesis is a validated drug target in malaria because antibiotics that inhibit translation in prokaryotes also inhibit apicoplast protein synthesis and are sometimes used for malaria prophylaxis or treatment. We identified components of an indirect aminoacylation pathway for Gln-tRNAGln biosynthesis in Plasmodium that we hypothesized would be essential for apicoplast protein synthesis. Here, we report our characterization of the first enzyme in this pathway, the apicoplast glutamyl- tRNA synthetase (GluRS). We expressed the recombinant P. falciparum enzyme in Escherichia coli, showed that it is nondiscriminating because it glutamylates both apicoplast tRNAGlu and tRNA Gln, determined its kinetic parameters, and demonstrated its inhibition by a known bacterial GluRS inhibitor. We also localized the Plasmodium berghei ortholog to the apicoplast in blood stage parasites but could not delete the PbGluRS gene. These data show that Gln-tRNAGln biosynthesis in the Plasmodium apicoplast proceeds via an essential indirect aminoacylation pathway that is reminiscent of bacteria and plastids.

Original languageEnglish (US)
Pages (from-to)32539-32552
Number of pages14
JournalJournal of Biological Chemistry
Volume288
Issue number45
DOIs
StatePublished - Nov 8 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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