Cysteinyl-tRNA Synthetase

Cysteinyl-tRNA synthetase (CysRS) is an enzyme that plays a crucial role in protein synthesis by catalysing the attachment of cysteine to its cognate tRNA: $ \text{Cys} + \text{tRNA}^\text{Cys} + \text{ATP} \xrightarrow{\text{CysRS}} \text{Cys-tRNA}^\text{Cys} + \text{AMP} + \text{PP}_i $ Unlike many other AARS, CysRS does not require editing activity to attain its remarkable degree of specificity, and is able to discriminate against alanine and serine quite effectively (Fersht et al. 1979, Hou and Perona, 2005). This is explained by the use of zinc ions that coordinate cysteine binding, a mechanism facilitated by conserved side chains of cysteine and histidine residues in the active site (Newberry et al. 2002). Anticodon loop recognition is achieved by the C-terminal $\alpha/\beta$ domain (Hauenstein et al. 2004). This resides downstream from the helical [anticodon binding domain](/superfamily/class1/Anticodon_binding_domain_CRIMVL) (Hou and Perona, 2005), which is also found in [ArgRS](/class1/arg), [LeuRS](/class1/leu1), [ValRS](/class1/val), [MetRS](/class1/met), and [IleRS](/class1/ile). In CysRS however, the helical domain is substantially smaller and recognizes the anticodon and D stems, rather than the anticodon loop (Hauenstein et al. 2004). Acceptor stem recognition may be further coordinated by a disordered module on the surface of the catalytic domain (Newberry et al. 2002) - the CysRS insertion module. CysRS behaves as a monomer in some organisms, and as a homodimer in others (Motorin et al. 1997). While eukaryotes typically possess distinct genes encoding cytosolic and mitochondrial CysRS, yeast produces both forms from a single CysRS gene using alternative transcription start sites (Nishimura et al. 2019). The enzyme is lacking in many methanogenic archaea, which instead utilize [SepRS](/class2/sep) to encode cysteine (Sauerwald et al. 2005).

References

Hou, Ya-Ming and John J. Perona. "The Aminoacyl-tRNA Synthetases" CRC Press (2005): Chapter 3: Cysteinyl-tRNA Synthetases. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. Douglas, J, Bouckaert, R., Carter, C., & Wills, P. R. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Research Square (2023). Fersht, Alan R., and Colin Dingwall. "Cysteinyl-tRNA synthetase from Escherichia coli does not need an editing mechanism to reject serine and alanine. High binding energy of small groups in specific molecular interactions." Biochemistry 18.7 (1979): 1245-1249. Sauerwald, Anselm, et al. "RNA-dependent cysteine biosynthesis in archaea." Science 307.5717 (2005): 1969-1972. Newberry, Kate J., Ya-Ming Hou, and John J. Perona. "Structural origins of amino acid selection without editing by cysteinyl-tRNA synthetase." The EMBO journal 21.11 (2002): 2778-2787. Motorin, Y., J. P. Le Caer, and J. P. Waller. "Cysteinyl-tRNA synthetase from Saccharomyces cerevisiae. Purification, characterization and assignment to the genomic sequence YNL247w." Biochimie 79.12 (1997): 731-740. Hauenstein, Scott, et al. "Shape-selective RNA recognition by cysteinyl-tRNA synthetase." Nature structural & molecular biology 11.11 (2004): 1134-1141. Nishimura, Akira, et al. "Mitochondrial cysteinyl-tRNA synthetase is expressed via alternative transcriptional initiation regulated by energy metabolism in yeast cells." Journal of Biological Chemistry 294.37 (2019): 13781-13788.