Prolyl-tRNA Synthetase (Archaeal-like)

The archaeal-like prolyl-tRNA synthetase (ProRS-A) 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-A}} \text{Pro-tRNA}^\text{Pro} + \text{AMP} + \text{PP}_i $ ProRS-A is closely related to [ProRS-B](/class2/pro2), which is found in most 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 and Ibba 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).

References

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