Prolyl-tRNA Synthetase (Bacterial-like)

The bacterial-like prolyl-tRNA synthetase (ProRS-B) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid proline to its cognate tRNA: $ \text{Pro} + \text{tRNA}^\text{Pro} + \text{ATP} \xrightarrow{\text{ProRS-B}} \text{Pro-tRNA}^\text{Pro} + \text{AMP} + \text{PP}_i $ ProRS-B is closely related to [ProRS-A](/class2/pro1), which is found in archaea, eukaryotic cytosols, and some bacteria, and [ProRS-M](/class2/pro3), which is localized to organelles. They possess distinct domain architectures (Musier-Forsyth et al. 2005). ProRS-B contains an editing domain inserted within the catalytic domain, while ProRS-A has a C-terminal zinc binding domain that is around 80 amino acids in length. The functional activity of the zinc binding domain remains unclear, but it appears to be essential for ProRS catalytic activity (Vasu et al. 2021). The three types of ProRS belong to subclass IIa, which includes other enzymes such as [ThrRS](/class2/thr), [SerRS](/class2/ser1), and the dimeric [GlyRS](/class2/gly1) (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 ProRS 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). Post-transfer editing allows the removal of mischarged residues from $\text{tRNA}^\text{Pro}$. In ProRS-B, the deacylation of mischarged cysteine and alanine can occur through an edit domain located between motifs 2 and 3 of the catalytic domain. This process is quite inefficient for cysteine in particular, and the domain is lacking entirely from ProRS-A. As such, there are trans-acting factors which remove these mischarged residues from $\text{tRNA}^\text{Pro}$, such as YbaK for cysteine and ProXp-ala for alanine. These factors are paralogs of the ProRS-B editing domain (Vargas-Rodriguez and Musier-Forsyth 2013, An and Musier-Forsyth 2004). A fused glutamyl-prolyl tRNA synthetase (EPRS) also exists in most animals (Berthonneau et al. 2000). This protein contains the catalytic domains from both GluRS and ProRS-A, as well as the ProRS-A zinc binding domain. Glutamic acid is a metabolic precursor for proline, which suggests a possible explanation for the origin of this protein (Eswarappa et al. 2018).

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). An, Songon, and Karin Musier-Forsyth. "Trans-editing of Cys-tRNAPro by Haemophilus influenzae YbaK protein." Journal of Biological Chemistry 279.41 (2004): 42359-42362. Danhart, Eric M., et al. "Conformational and chemical selection by a trans-acting editing domain." Proceedings of the National Academy of Sciences 114.33 (2017): E6774-E6783. Vasu, Kommireddy, et al. "The zinc-binding domain of mammalian prolyl-tRNA synthetase is indispensable for catalytic activity and organism viability." Iscience 24.3 (2021): 102215. Vargas-Rodriguez, Oscar, and Karin Musier-Forsyth. "Exclusive use of trans-editing domains prevents proline mistranslation." Journal of Biological Chemistry 288.20 (2013): 14391-14399. 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. Musier-Forsyth, Karin, et al. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 15: Prolyl-tRNA Synthetases. Eswarappa, Sandeep M., et al. "Metabolic origin of the fused aminoacyl-tRNA synthetase, glutamyl-prolyl-tRNA synthetase." Journal of Biological Chemistry 293.49 (2018): 19148-19156.