Discriminating Aspartyl-tRNA Synthetase

The discriminating aspartyl tRNA synthetase (AspRS) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid aspartate to its cognate tRNA: $ \text{Asp} + \text{tRNA}^\text{Asp} + \text{ATP} \xrightarrow{\text{AspRS}} \text{Asp-tRNA}^\text{Asp} + \text{AMP} + \text{PP}_i $ This reaction enables the incorporation of aspartate into the polypeptide. There is also a non-discriminating [AsxRS](/class2/asp2) that can also incorporate both aspartate and asparagine into the growing peptide. A helix in the anticodon binding domain may enable AspRS to discriminate between the two tRNA species (Charron et al. 2003). Some organisms contain genes for both proteins. The three-dimensional structure of AsnRS closely resembles that of AsxRS, [AsnRS](/class2/asn/), and [LysRS-II](/class2/lys/), with an N-terminal [anticodon binding domain](/superfamily/class2/Anticodon_binding_domain_DNK/) and a C-terminal catalytic domain. The four members have quite similar catalytic domains and constitute subclass IIb (Cusack et al., 1991; Valencia-Sánchez et al., 2016). The subclass IIb synthetases of many eukaryotes contain a flexible domain at their N-termini, which helps to anchor the synthetase onto the tRNA (Frugier et al., 2000). Editing activity has not been detected for AspRS (Gomez abd Ibba, 2020). The C-terminal catalytic domain of AspRS is quite typical of a Class II AARS. Like most members of the superfamily, ATP binding is coordinated by the arginine tweezers, located in motifs 2 and 3 (Kaiser et al., 2018). The catalytic domain of AspRS, much like the other members of subclass IIb, is characterized by the subclass IIb insertion modules 1 and 2. In the special case of AspRS, the first insertion module is considerably more elaborated than the rest of the subclass (Douglas et al. 2023). This extensive module makes up a five-stranded antiparallel $\beta$-sheet flanked by $\alpha$-helices that interacts with the tRNA through a network of water molecules (Eiler et al. 1999).

References

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