Skip to main content
SpringerLink
Log in

Expanding chemical biology of 2-oxoglutarate oxygenases

  • Commentary
  • Published:

From Nature Chemical Biology

View current issue Submit your manuscript

Abstract

Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate–dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a multiplicity of histone modifications has some analogy with their role in enabling structural diversity in secondary metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Known and proposed roles for human 2OG oxygenases with outline catalytic cycle.
Figure 2: Overall folds and active sites of human 2OG oxygenases.
Figure 3: The combinatorial and dynamic nature of covalent modifications to the histone H3 N terminus, highlighting the role of 2OG oxygenases, and their role in introducing diversity into peptide-derived secondary metabolites.

Accession codes

Accessions

Protein Data Bank

References

  1. Hutton, J.J. Jr., Kaplan, A. & Udenfriend, S. Arch. Biochem. Biophys. 121, 384–391 (1967).

    Article  CAS  PubMed  Google Scholar 

  2. Costas, M., Mehn, M.P., Jensen, M.P. & Que, L. Chem. Rev. 104, 939–986 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Ozer, A. & Bruick, R.K. Nat. Chem. Biol. 3, 144–153 (2007).

    Article  CAS  PubMed  Google Scholar 

  4. Clifton, I.J. et al. J. Inorg. Biochem. 100, 644–669 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Flashman, E. & Schofield, C.J. Nat. Chem. Biol. 3, 86–87 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Schofield, C.J. & McDonough, M.A. Biochem. Soc. Trans. 35, 870–875 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Vaz, F.M. & Wanders, R.J. Biochem. J. 361, 417–429 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Coleman, M.L. & Ratcliffe, P.J. Essays Biochem. 43, 1–15 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Jenkins, C.L. & Raines, R.T. Nat. Prod. Rep. 19, 49–59 (2002).

    Article  CAS  PubMed  Google Scholar 

  10. Myllyharju, J. & Kivirikko, K.I. Trends Genet. 20, 33–43 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Dinchuk, J.E. et al. J. Biol. Chem. 277, 12970–12977 (2002).

    Article  CAS  PubMed  Google Scholar 

  12. Cockman, M.E. et al. Proc. Natl. Acad. Sci. USA 103, 14767–14772 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Coleman, M.L. et al. J. Biol. Chem. 282, 24027–24038 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Ferguson, J.E. III et al. Mol. Cell. Biol. 27, 6407–6419 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sedgwick, B., Bates, P.A., Paik, J., Jacobs, S.C. & Lindahl, T. DNA Repair (Amst.) 6, 429–442 (2007).

    Article  CAS  Google Scholar 

  16. Ringvoll, J. et al. EMBO J. 25, 2189–2198 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Frayling, T.M. et al. Science 316, 889–894 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gerken, T. et al. Science 318, 1469–1472 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kouzarides, T. Cell 128, 693–705 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Klose, R.J. & Zhang, Y. Nat. Rev. Mol. Cell Biol. 8, 307–318 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Tsukada, Y.-I. et al. Nature 439, 811–816 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Shi, Y. Nat. Rev. Genet. 8, 829–833 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Cikala, M. et al. BMC Cell Biol. 5, 26 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chang, B., Chen, Y., Zhao, Y. & Bruick, R.K. Science 318, 444–447 (2007).

    Article  CAS  PubMed  Google Scholar 

  25. Bose, J. et al. J. Biol. 3, 15 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ng, S.S. et al. Nature 448, 87–91 (2007).

    Article  CAS  PubMed  Google Scholar 

  27. Chen, Z. et al. Proc. Natl. Acad. Sci. USA 104, 10818–10823 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Chen, H. et al. Biochemistry 40, 11651–11659 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Strieker, M., Kopp, F., Mahlert, C., Essen, L.-O. & Marahiel, M.A. ACS Chem. Biol. 2, 187–196 (2007).

    Article  CAS  PubMed  Google Scholar 

  30. Agger, K. et al. Nature 449, 731–734 (2007).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Biotechnology and Biological Sciences Research Council, the Wellcome Trust and the Rhodes Trust (C.L.) for funding.

Author information

Authors and Affiliations

  1. Christoph Loenarz and Christopher J. Schofield are in the Chemistry Research Laboratory and the Oxford Centre for Integrative Systems Biology, Mansfield Road, Oxford OX1 3TA, UK. christopher.schofield@chem.ox.ac.uk,

    Christoph Loenarz & Christopher J Schofield

Authors
  1. Christoph Loenarz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher J Schofield
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

C.J.S. is a cofounder of ReOx, a company that aims to exploit scientific discoveries on the hypoxic response for medicinal use.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loenarz, C., Schofield, C. Expanding chemical biology of 2-oxoglutarate oxygenases. Nat Chem Biol 4, 152–156 (2008). https://doi.org/10.1038/nchembio0308-152

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio0308-152

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation