Asparaginyl-tRNA Synthetase

Asparaginyl-tRNA synthetase (AsnRS) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the amino acid asparagine to its cognate tRNA: $ \text{Asn} + \text{tRNA}^\text{Asn} + \text{ATP} \xrightarrow{\text{AsnRS}} \text{Asn-tRNA}^\text{Asn} + \text{AMP} + \text{PP}_i $ Some organisms do not possess AsnRS, in which case the incorporation of asparagine into the polypeptide can be accomplished through the use of a non-discriminating [AsxRS](/class2/asp2/), coupled with amidotransferase activity (Becker et al. 1997, Raczniak et al. 2001). The same mechanism is employed by the Class I [GlxRS](/class1/glu2/) and [GlnRS](/class1/gln/) families, leading to the hypothesis that AsnRS and GlnRS were among the last of the synthetases to evolve (de Pouplana and Schimmel, 2001). The three-dimensional structure of AsnRS closely resembles that of AsxRS, [AspRS](/class2/asp1/), 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 AsnRS (Gomez and Ibba, 2020). The C-terminal catalytic domain of AsnRS 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). In the active site, asparagine recognition is largely achieved through water molecule interactions, in contrast with AspRS where aspartate recognition is facilitated by direct interaction with the protein (Iwasaki et al., 2006). This specificity is also achieved by the replacement of positively charged residues with negatively charged ones in the active site (Kern et al., 2005). The catalytic domain of AsnRS, much like the other members of subclass IIb, is characterized by the subclass IIb insertion modules 1 and 2 (Douglas et al. 2023).

References

Iwasaki, Wataru, et al. "Structural basis of the water-assisted asparagine recognition by asparaginyl-tRNA synthetase." Journal of molecular biology 360.2 (2006): 329-342. Douglas, J, Bouckaert, R., Carter, C., & Wills, P. R. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Research Square (2023). Cusack, Stephen, Michael Härtlein, and Reuben Leberman. "Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases." Nucleic acids research 19.13 (1991): 3489-3498. Frugier, Magali, Luc Moulinier, and Richard Giegé. "A domain in the N-terminal extension of class IIb eukaryotic aminoacyl-tRNA synthetases is important for tRNA binding." The EMBO Journal 19.10 (2000): 2371-2380. 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. Becker, Hubert Dominique, et al. "Existence of two distinct aspartyl-tRNA synthetases in Thermus thermophilus. Structural and biochemical properties of the two enzymes." Biochemistry 36.29 (1997): 8785-8797. 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. Kern, Daniel, et al. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 18: Asparaginyl-tRNA Synthetases. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. de Pouplana, Lluıs Ribas, and Paul Schimmel. "Operational RNA code for amino acids in relation to genetic code in evolution." Journal of Biological Chemistry 276.10 (2001): 6881-6884. Raczniak, Gregory, et al. "A single amidotransferase forms asparaginyl-tRNA and glutaminyl-tRNA in Chlamydia trachomatis." Journal of Biological Chemistry 276.49 (2001): 45862-45867.