Non-discriminating Aspartyl-tRNA Synthetase

This page describes two aspartyl-tRNA synthetase families. The discriminating eukaryotic aspartyl-tRNA synthetase (AspRS-E) 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-E}} \text{Asp-tRNA}^\text{Asp} + \text{AMP} + \text{PP}_i $ Whereas, the non-discriminating bacterial-like aspartyl-tRNA synthetase (AsxRS) catalyzes the following two reactions: $ \text{Asp} + \text{tRNA}^\text{Asp} + \text{ATP} \xrightarrow{\text{AsxRS}} \text{Asp-tRNA}^\text{Asn} + \text{AMP} + \text{PP}_i $ $ \text{Asp} + \text{tRNA}^\text{Asn} + \text{ATP} \xrightarrow{\text{AsxRS}} \text{Asp-tRNA}^\text{Asn} + \text{AMP} + \text{PP}_i $ This last reaction enables the incorporation of aspartate into the polypeptide, while the second enables incorporation of asparagine for organisms that lack [AsnRS](/class2/asn). An amidotransferase subsequently corrects $\text{Asp-tRNA}^\text{Asn}$ into $\text{Asn-tRNA}^\text{Asn}$ (Becker et al. 1997, Raczniak et al. 2001). There is also a discriminating [AspRS](/class2/asp1) which can carry out this first reaction but not the second one. AspRS exists in two forms which likely converged independently - the standard form AspRS found in bacteria, organelles, and archaea, and the eukaryote-like form AspRS-E, which displays high levels of sequence and structural similarity with AsxRS (Kern et al. 2013), and hence is detailed on this webpage. The three-dimensional structure of AsxRS closely resembles that of AsnRS, AspRS, 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). Many fungal AsxRS contain a C-terminal domain (DUF2156, Datt et al. 2014) which transfers aspartate from $\text{tRNA}^\text{Asp}$ onto ergosterol (Yakobov et al. 2020). Editing activity has not been detected for AsxRS (Gomez and Ibba, 2020). The C-terminal catalytic domain of AsxRS 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). Like the other members of subclass IIb, its catalytic domain is characterized by the subclass IIb insertion modules 1 and 2 (Douglas et al. 2023).

References

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