Plasmodium Apicoplast Gln-tRNAGln Biosynthesis Utilizes a Unique GatAB Amidotransferase Essential for Erythrocytic Stage Parasites
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The malaria parasite Plasmodium falciparum apicoplast indirect aminoacylation pathway utilizes a non-discriminating glutamyl-tRNA synthetase to synthesize Glu-tRNA(Gln) and a glutaminyl-tRNA amidotransferase to convert Glu-tRNA(Gln) to Gln-tRNA(Gln). Here, we show that Plasmodium falciparum and other apicomplexans possess a unique heterodimeric glutamyl-tRNA amidotransferase consisting of GatA and GatB subunits (GatAB). We localized the P. falciparum GatA and GatB subunits to the apicoplast in blood stage parasites and demonstrated that recombinant GatAB converts Glu-tRNA(Gln) to Gln-tRNA(Gln) in vitro. We demonstrate that the apicoplast GatAB-catalyzed reaction is essential to the parasite blood stages because we could not delete the Plasmodium berghei gene encoding GatA in blood stage parasites in vivo. A phylogenetic analysis placed the split between Plasmodium GatB, archaeal GatE, and bacterial GatB prior to the phylogenetic divide between bacteria and archaea. Moreover, Plasmodium GatA also appears to have emerged prior to the bacterial-archaeal phylogenetic divide. Thus, although GatAB is found in Plasmodium, it emerged prior to the phylogenetic separation of archaea and bacteria.
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Davison D, Howell S, Snijders A, Deu E iScience. 2022; 25(9):104996.
PMID: 36105595 PMC: 9464883. DOI: 10.1016/j.isci.2022.104996.
Jaramillo Ponce J, Kapps D, Paulus C, Chicher J, Frugier M J Biol Chem. 2022; 298(6):101987.
PMID: 35487244 PMC: 9136112. DOI: 10.1016/j.jbc.2022.101987.
Antimalarial Peptide and Polyketide Natural Products from the Fijian Marine Cyanobacterium .
Sweeney-Jones A, Gagaring K, Antonova-Koch J, Zhou H, Mojib N, Soapi K Mar Drugs. 2020; 18(3).
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Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study.
Nyamai D, Tastan Bishop O Malar J. 2019; 18(1):34.
PMID: 30728021 PMC: 6366043. DOI: 10.1186/s12936-019-2665-6.