Glutamyl-tRNA Synthetase (Bacterial-like)

This page describes two glutamyl-tRNA synthetase families predominant in bacteria. The discriminating bacterial-like glutamyl-tRNA synthetase (GluRS-B) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid glutamate to its cognate tRNA: $ \text{Glu} + \text{tRNA}^\text{Glu} + \text{ATP} \xrightarrow{\text{GluRS-B}} \text{Glu-tRNA}^\text{Glu} + \text{AMP} + \text{PP}_i $ Whereas, the non-discriminating bacterial-like glutamyl-tRNA synthetase (GlxRS-B) catalyzes the following two reactions: $ \text{Glu} + \text{tRNA}^\text{Glu} + \text{ATP} \xrightarrow{\text{GlxRS-B}} \text{Glu-tRNA}^\text{Glu} + \text{AMP} + \text{PP}_i $ $ \text{Glu} + \text{tRNA}^\text{Gln} + \text{ATP} \xrightarrow{\text{GlxRS-B}} \text{Glu-tRNA}^\text{Gln} + \text{AMP} + \text{PP}_i $ As discussed by Hadd and Perona 2014, there is a complex coevolutionary history between glutamyl- and glutaminyl-tRNA synthetases, which comprise subclass Ib (Perona and Hadd. 2012, Gomez et al., 2020). Their diversification occurred after the last universal common ancestor, with bacterial-like forms being characterized by an [$\alpha$-helical anticodon binding domain](/superfamily/class1/Anticodon_binding_domain_EK), and the archaeal and eukaryotic forms possessing a [$\beta$-barrel anticodon binding domain](/superfamily/class1/Anticodon_binding_domain_EQ). While many contemporary systems express both GlnRS and GluRS, their ancestor was most likely a non-discriminating form, which would attach Glu to tRNA$^\text{Gln}$. A second enzymic step, performed by an amidotransferase, would correct the misacylated tRNA prior to protein synthesis, as it does with [AsxRS](/class2/asp2/) (Lapointe et al. 1986, Raczniak et al. 2001). This non-discriminating enzyme is still found in systems which lack GlnRS, such the archaea, which express [GlxRS-A](/class1/glu2/), as well as certain bacteria which have a non-discriminating variant [GlxRS-B](/class1/glu1/), or a noncognate variant GluGlnRS which attaches Glu to tRNA$^\text{Gln}$ (Salazar et al. 2003, Skouloubris et al. 2003). It is likely that GlnRS originated in the eukaryota, and was later acquired by certain bacteria through horizontal gene transfer (Siatecka et al. 1998). GluRS-B and GlxRS-B are the bacterial counterparts to the eurarchaeal [GluRS-E](/class1/glu3) and GlxRS-A, respectively, differentiated by their distinct catalytic domain sequences and anticodon binding domain structures. Under normal circumstances, the two families GluRS-B and GlxRS-B would be split into two distinct webpages in this database since they have distinct aminoacylation functions. However, GluRS-B and GlxRS-B are challenging to distinguish using sequence-based comparisons (Schulze et al. 2006), and hence their putative functional assignments are unified in a single alignment below. The N-terminal catalytic domains of GluRS-B and GlxRS-B closely resembles the other members of subclass Ib: GlnRS, GlxRS-A, and GluRS-E. Their catalytic domains are characterized by an insertion within CP1, containing a loop flanked by two helices (SC1b IM), which may play a role in acceptor stem recognition (Rath et al. 1998, Nureki et al. 2010). The $\alpha$-helical anticodon binding domain of GluRS-B and GlxRS-B are located at their C-terminal ends and are homologous with that of [LysRS-I](/class1/lys/) (Terada et al. 2002), in contrast to the other members of Ib, which instead have a $\beta$-barrel anticodon binding domain of archaeal origin. The members of subclass Ib, alongside LysRS-I and [ArgRS](/class1/arg/), require the presence of tRNA to catalyze activation of the amino acid substrate (Dubois et al. 2005).

References

Douglas, J, Bouckaert, R., Carter, C., & Wills, P. R. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Research Square (2023). Daniel Y. Dubois, Jacques Lapointe and Shun-ichi Sekine. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 10: Glutamyl-tRNA Synthetases. Raczniak, Gregory, et al. "A single amidotransferase forms asparaginyl-tRNA and glutaminyl-tRNA in Chlamydia trachomatis." Journal of Biological Chemistry 276.49 (2001): 45862-45867. Lapointe JA, Duplain LO, Proulx MA. A single glutamyl-tRNA synthetase aminoacylates tRNAGlu and tRNAGln in Bacillus subtilis and efficiently misacylates Escherichia coli tRNAGln1 in vitro. Journal of Bacteriology. 1986 Jan;165(1):88-93. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. Hadd, Andrew, and John J. Perona. "Coevolution of specificity determinants in eukaryotic glutamyl-and glutaminyl-tRNA synthetases." Journal of molecular biology 426.21 (2014): 3619-3633. Perona, John J., and Andrew Hadd. "Structural diversity and protein engineering of the aminoacyl-tRNA synthetases." Biochemistry 51.44 (2012): 8705-8729. Rath, Virginia L., et al. "How glutaminyl-tRNA synthetase selects glutamine." Structure 6.4 (1998): 439-449. Nureki, Osamu, et al. "Structure of an archaeal non-discriminating glutamyl-tRNA synthetase: a missing link in the evolution of Gln-tRNAGln formation." Nucleic acids research 38.20 (2010): 7286-7297. Terada, Takaho, et al. "Functional convergence of two lysyl-tRNA synthetases with unrelated topologies." nature structural biology 9.4 (2002): 257-262. Berthonneau, Eric, and Marc Mirande. "A gene fusion event in the evolution of aminoacyl-tRNA synthetases." FEBS letters 470.3 (2000): 300-304. Skouloubris, Stéphane, et al. "A noncognate aminoacyl-tRNA synthetase that may resolve a missing link in protein evolution." Proceedings of the National Academy of Sciences 100.20 (2003): 11297-11302. Salazar, Juan C., et al. "Coevolution of an aminoacyl-tRNA synthetase with its tRNA substrates." Proceedings of the National Academy of Sciences 100.24 (2003): 13863-13868. Schulze, Jörg O., et al. "Crystal structure of a non-discriminating glutamyl-tRNA synthetase." Journal of molecular biology 361.5 (2006): 888-897. Siatecka, Miroslawa, et al. "Modular evolution of the Glx‐tRNA synthetase family: Rooting of the evolutionary tree between the bacteria and archaea/eukarya branches." European Journal of Biochemistry 256.1 (1998): 80-87.