Glycyl-tRNA Synthetase (Archaeal-like)

The Archaeal-like glycyl-tRNA synthetase (GlyRS-A) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid glycine to its cognate tRNA: $ \text{Gly} + \text{tRNA}^\text{Gly} + \text{ATP} \xrightarrow{\text{GlyRS-A}} \text{Gly-tRNA}^\text{Gly} + \text{AMP} + \text{PP}_i $ GlyRS-A is a homodimeric enzyme found in archaea and some bacteria, and is closely related to the eukaryote-like form [GlyRS-E](/class2/gly3). The two families have a catalytic domain characterized by the presence of two insertion modules, GlyRS insertion modules 1 and 2, which are located between motifs 2 and 3. Insertion module 1 contains a short $\beta$ strand which runs parallel with the six stranded anti-parallel fold, and likely recognises the acceptor stem (Qin et al. 2014). Insertion module 2 is absent in bacteria. GlyRS-E is further distinguished by an additional insertion module nested within the catalytic domain. These two forms differ from the bacterial-like form [GlyRS-B](/class2/gly2), which operates as a heterotetramer and is phylogenetically distinct (Shiba 2005). GlyRS-A and -E belong to subclass IIa, which includes other enzymes such as [ProRS](/class2/pro1), [SerRS](/class2/ser1), and [ThrRS](/class2/thr) (Gomez et al. 2020, Valencia-Sánchez et al. 2016, Perona et al. 2012). The [anticodon binding domains](/superfamily/class2/Anticodon_binding_domain_HGPT) of subclass IIa, with the exception of SerRS, are homologous with that of [HisRS](/class2/his), and are located at the C-terminal end (Wolf et al. 1999). The catalytic domain of GlyRS is typical of a Class II aminoacyl-tRNA synthetase. Like most members of the superfamily, ATP binding is coordinated by the arginine tweezers, located in motifs 2 and 3 (Kaiser et al. 2018). GlyRS-A appears to lack editing activity altogether (Gomez et al. 2020).

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). Wolf, Yuri I., et al. "Evolution of aminoacyl-tRNA synthetases—analysis of unique domain architectures and phylogenetic trees reveals a complex history of horizontal gene transfer events." Genome research 9.8 (1999): 689-710. Perona, John J., and Andrew Hadd. "Structural diversity and protein engineering of the aminoacyl-tRNA synthetases." Biochemistry 51.44 (2012): 8705-8729. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. Valencia-Sánchez, Marco Igor, et al. "Structural Insights into the Polyphyletic Origins of Glycyl tRNA Synthetases." Journal of Biological Chemistry 291.28 (2016): 14430-14446. Kaiser, Florian, et al. "Backbone brackets and arginine tweezers delineate class I and class II aminoacyl tRNA synthetases." PLoS computational biology 14.4 (2018): e1006101. Shiba, Kiyotaka. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 13: Glycyl-tRNA Synthetases. Chen, Shun-Jia, et al. "Rescuing a dysfunctional homologue of a yeast glycyl-tRNA synthetase gene." ACS Chemical Biology 6.11 (2011): 1182-1187. Guo, Rey-Ting, et al. "Crystal Structures and Biochemical Analyses Suggest a Unique Mechanism and Role for Human Glycyl-tRNA Synthetase in Ap4A Homeostasis." Journal of Biological Chemistry 284.42 (2009):28968–28976. Xie, Wei, et al. "Long-range structural effects of a Charcot–Marie–Tooth disease-causing mutation in human glycyl-tRNA synthetase." PNAS 104.24 (2007):9976-9981. Qin, Xiangjing , et al. "Crystal Structure of the Wild-Type Human GlyRS Bound with tRNA Gly in a Productive Conformation." Journal of Molecular Biology 428.18 (2016):3603–3614. Qin, Xiangjing, et al. "Cocrystal structures of glycyl-tRNA synthetase in complex with tRNA suggest multiple conformational states in glycylation." Journal of Biological Chemistry 289.29 (2014): 20359-20369.