O-phosphoseryl-tRNA Synthetase

O-phosphoseryl-tRNA synthetase (SepRS) is an enzyme that plays a crucial role in protein synthesis by catalyzing the attachment of the non-proteinogenic amino acid o-phosphoserine to the tRNA of cysteine: $ \text{Sep} + \text{tRNA}^\text{Cys} + \text{ATP} \xrightarrow{\text{SepRS}} \text{Sep-tRNA}^\text{Cys} + \text{AMP} + \text{PP}_i $ In certain methanogenic archaea, the standard Class I [CysRS](/class1/cys/) is absent, thus, the non-canonical SepRS charges $\text{tRNA}^\text{Cys}$ with o-phosphoserine, which is then converted into cysteine by Cys-tRNA synthetase (Sauerwald et al. 2005). Unlike most Class II synthetases, SepRS exists as a homotetramer (Fukunaga and Shigeyuki 2007). The catalytic domain of SepRS shares structural similarities with that of [HisRS](/class2/his) and [PheRS](/class2/phe1), which comprise subclass IIc (Douglas et al. 2023, Kavran et al. 2007, Perona et al. 2012, Valencia-Sánchez et al. 2016). The catalytic domain is typical among class II enzymes, containing six antiparallel strands. The binding of ATP is coordinated by the arginine tweezers, located in motifs 2 and 3 (Kaiser et al. 2018). The catalytic domain is characterized by the 70-80 residue SepRS insertion module, which resides between motifs 1 and 2 (Douglas et al. 2023). This module is intrinsically disordered (Kamtekar et a. 2007). The C-terminal domain recognises the anticodon of $\text{tRNA}^\text{Cys}$ (Fukunaga and Shigeyuki 2007). Editing has not been observed in SerRS-A (Gomez et al. 2020).

References

Douglas, J, Bouckaert, R., Carter, C., & Wills, P. R. Enzymic recognition of amino acids drove the evolution of primordial genetic codes. Research Square (2023). Fukunaga, Ryuya, and Shigeyuki Yokoyama. "Structural insights into the first step of RNA-dependent cysteine biosynthesis in archaea." Nature structural & molecular biology 14.4 (2007): 272-279. Sauerwald, Anselm, et al. "RNA-dependent cysteine biosynthesis in archaea." Science 307.5717 (2005): 1969-1972. Kavran, Jennifer M., et al. "Structure of pyrrolysyl-tRNA synthetase, an archaeal enzyme for genetic code innovation." Proceedings of the National Academy of Sciences 104.27 (2007): 11268-11273. Kamtekar, Satwik, et al. "Toward understanding phosphoseryl-tRNACys formation: the crystal structure of Methanococcus maripaludis phosphoseryl-tRNA synthetase." Proceedings of the National Academy of Sciences 104.8 (2007): 2620-2625. 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. Gomez, Miguel Angel Rubio, and Michael Ibba. "Aminoacyl-tRNA synthetases." Rna 26.8 (2020): 910-936. 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. Perona, John J., and Andrew Hadd. "Structural diversity and protein engineering of the aminoacyl-tRNA synthetases." Biochemistry 51.44 (2012): 8705-8729.