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New Developments in Selenium Biochemistry: Selenocysteine Biosynthesis in Eukaryotes and Archaea

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Abstract

We used comparative genomics and experimental analyses to show that (1) eukaryotes and archaea, which possess the selenocysteine (Sec) protein insertion machinery contain an enzyme, O-phosphoseryl-transfer RNA (tRNA)[Ser]Sec kinase (designated PSTK), which phosphorylates seryl-tRNA[Ser]Sec to form O-phosphoseryl-tRNA[Ser]Sec and (2) the Sec synthase (SecS) in mammals is a pyridoxal phosphate-containing protein previously described as the soluble liver antigen (SLA). SecS uses the product of PSTK, O-phosphoseryl-tRNA[Ser]Sec, and selenophosphate as substrates to generate selenocysteyl-tRNA[Ser]Sec. Sec could be synthesized on tRNA[Ser]Sec from selenide, adenosine triphosphate (ATP), and serine using tRNA[Ser]Sec, seryl-tRNA synthetase, PSTK, selenophosphate synthetase, and SecS. The enzyme that synthesizes monoselenophosphate is a previously identified selenoprotein, selenophosphate synthetase 2 (SPS2), whereas the previously identified mammalian selenophosphate synthetase 1 did not serve this function. Monoselenophosphate also served directly in the reaction replacing ATP, selenide, and SPS2, demonstrating that this compound was the active selenium donor. Conservation of the overall pathway of Sec biosynthesis suggests that this pathway is also active in other eukaryotes and archaea that contain selenoproteins.

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Acknowledgements

This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research, by grants GM061603, GM065204, and CA080946 to VNG, grants DK47320 and DK52963 to MJB, and grant CA-41108 (NIH Colon Cancer Prevention Program Project) to RSG.

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Authors and Affiliations

  1. Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Institutes of Health, Bethesda, MD, 20892, USA

    Xue-Ming Xu, Bradley A. Carlson & Dolph L. Hatfield

  2. Department of Biochemistry, University of Nebraska, Lincoln, NE, 68588, USA

    Yan Zhang, Heiko Mix, Gregory V. Kryukov & Vadim N. Gladyshev

  3. Department of Chemistry, The University of Arizona, Tucson, AZ, 85721, USA

    Richard S. Glass

  4. Department of Cell and Molecular Biology, University of Hawaii at Manoa, Honolulu, HI, 96813, USA

    Marla J. Berry

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  1. Xue-Ming Xu
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  2. Bradley A. Carlson
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  3. Yan Zhang
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  4. Heiko Mix
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  5. Gregory V. Kryukov
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  6. Richard S. Glass
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  7. Marla J. Berry
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  8. Vadim N. Gladyshev
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  9. Dolph L. Hatfield
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Corresponding author

Correspondence to Dolph L. Hatfield.

Additional information

X.-M. Xu and B. A. Carlson contributed equally to the studies described herein.

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Xu, XM., Carlson, B.A., Zhang, Y. et al. New Developments in Selenium Biochemistry: Selenocysteine Biosynthesis in Eukaryotes and Archaea. Biol Trace Elem Res 119, 234–241 (2007). https://doi.org/10.1007/s12011-007-8003-9

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  • DOI: https://doi.org/10.1007/s12011-007-8003-9

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