| Structural highlights
Function
SYE_ECOLI Catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu).[1] [2] [3] [4] [5] Phosphorylation of GltX by HipA prevents it from being charged, leading to an increase in uncharged tRNA(Glu). This induces amino acid starvation and the stringent response via RelA/SpoT and increased (p)ppGpp levels, which inhibits replication, transcription, translation and cell wall synthesis, reducing growth and leading to multidrug resistance and persistence (PubMed:24095282, PubMed:24343429). Overexpression of GltX prevents HipA-induced growth arrest, persister formation and increases in (p)ppGpp levels (PubMed:24343429, PubMed:28430938).[6] [7] [8]
References
- ↑ Banerjee R, Dubois DY, Gauthier J, Lin SX, Roy S, Lapointe J. The zinc-binding site of a class I aminoacyl-tRNA synthetase is a SWIM domain that modulates amino acid binding via the tRNA acceptor arm. Eur J Biochem. 2004 Feb;271(4):724-33. PMID:14764088 doi:10.1111/j.1432-1033.2003.03976.x
- ↑ Kern D, Lapointe J. The catalytic mechanism of glutamyl-tRNA synthetase of Escherichia coli. Evidence for a two-step aminoacylation pathway, and study of the reactivity of the intermediate complex. Eur J Biochem. 1980 May;106(1):137-50 PMID:6280993
- ↑ Kern D, Lapointe J. The catalytic mechanism of the glutamyl-tRNA synthetase from Escherichia coli. Detection of an intermediate complex in which glutamate is activated. J Biol Chem. 1980 Mar 10;255(5):1956-61 PMID:6986385
- ↑ Liu J, Gagnon Y, Gauthier J, Furenlid L, L'Heureux PJ, Auger M, Nureki O, Yokoyama S, Lapointe J. The zinc-binding site of Escherichia coli glutamyl-tRNA synthetase is located in the acceptor-binding domain. Studies by extended x-ray absorption fine structure, molecular modeling, and site-directed mutagenesis. J Biol Chem. 1995 Jun 23;270(25):15162-9. PMID:7797500 doi:10.1074/jbc.270.25.15162
- ↑ Liu J, Lin SX, Blochet JE, Pézolet M, Lapointe J. The glutamyl-tRNA synthetase of Escherichia coli contains one atom of zinc essential for its native conformation and its catalytic activity. Biochemistry. 1993 Oct 26;32(42):11390-6. PMID:8218204 doi:10.1021/bi00093a016
- ↑ Germain E, Castro-Roa D, Zenkin N, Gerdes K. Molecular mechanism of bacterial persistence by HipA. Mol Cell. 2013 Oct 24;52(2):248-54. PMID:24095282 doi:10.1016/j.molcel.2013.08.045
- ↑ Kaspy I, Rotem E, Weiss N, Ronin I, Balaban NQ, Glaser G. HipA-mediated antibiotic persistence via phosphorylation of the glutamyl-tRNA-synthetase. Nat Commun. 2013;4:3001. PMID:24343429 doi:10.1038/ncomms4001
- ↑ Maeda Y, Lin CY, Ishida Y, Inouye M, Yamaguchi Y, Phadtare S. Characterization of YjjJ toxin of Escherichia coli. FEMS Microbiol Lett. 2017 Jun 15;364(11). PMID:28430938 doi:10.1093/femsle/fnx086
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