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Se-ing into selenocysteine biosynthesis

Nature Chemical Biology volume 5, pages 611–612 (2009)Cite this article

A cocrystal structure of the enzyme that synthesizes selenocysteine reveals the elegantly simple recognition mechanism for the tRNA molecule for this '21st amino acid'. The structure resolves some mechanistic questions and allows for comparison of the tRNA-dependent synthesis of cysteine and selenocysteine.

Selenium is an essential trace element found in both RNA and proteins. The latter contain selenocysteine, the analog of cysteine in which the sulfur is replaced with its immediate downstairs neighbor in the periodic table. Selenocysteine is found in several essential enzymes, and the activities of these enzymes depend on its presence. The discovery of the selenoproteins set in motion searches for the means by which selenocysteine is made and incorporated into proteins. A unique transfer RNA (tRNASec) recognizes an in-frame UGA stop codon when a selenium insertion sequence is also present and thus allows for the translational incorporation of selenocysteine in proteins. The biosynthesis of selenocysteine occurs on the same tRNA, which is first acylated with serine that is subsequently transformed into selenocysteine by a synthase that uses selenophosphate as the selenium donor and the cofactor pyridoxal phosphate. Palioura et al.1 have now solved the crystal structure of the human synthase bound with tRNASec, phosphoserine and thiophosphate (a selenophosphate mimic). The new study provides the first structural determination of tRNASec, illuminates how the enzyme chooses it over other tRNAs, and allows the inference of important details of the chemical mechanism.

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Figure 1: Synthesis of selenocysteine by SepSecS.

References

  1. Palioura, S. et al. Science 325, 321–325 (2009).

    Article  CAS  Google Scholar 

  2. Forchhammer, K. & Böck, A. J. Biol. Chem. 266, 6324–6328 (1991).

    CAS  PubMed  Google Scholar 

  3. Yuan, J. et al. Proc. Natl. Acad. Sci. USA 103, 18923–18927 (2006).

    Article  CAS  Google Scholar 

  4. Xu, X.-M. et al. PLoS Biol. 5, e4 (2007).

    Article  Google Scholar 

  5. Ganichkin, O.M. et al. J. Biol. Chem. 283, 5849–5865 (2008).

    Article  CAS  Google Scholar 

  6. Araiso, Y. et al. Nucleic Acids Res. 36, 1187–1199 (2008).

    Article  CAS  Google Scholar 

  7. Hauenstein, S.I. & Perona, J.J. J. Biol. Chem. 283, 22007–22017 (2008).

    Article  CAS  Google Scholar 

Download references

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  1. Eugene G. Mueller is the Charles L. Bloch Professor in the Department of Chemistry, University of Louisville, Louisville, Kentucky, USA. eugene.mueller@louisville.edu,

    Eugene G Mueller

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  1. Eugene G Mueller
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Mueller, E. Se-ing into selenocysteine biosynthesis. Nat Chem Biol 5, 611–612 (2009). https://doi.org/10.1038/nchembio0909-611

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