Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Divide and conquer: the E2 active site

The E2 enzymes for ubiquitin and SUMO conjugation share a conserved active site that has long been mysterious for lack of identifiable catalytic residues. In an elegant tour de force, it is now shown how three E2 residues not only position the target lysine but also substantially lower its pK to allow deprotonation and efficient substrate transfer.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic view of the multistep process of protein modification, showing the transfer of ubiquitin(-like) proteins (yellow) from E1 to E2 and then, with the help of an E3, to the target.
Figure 2: Divided activation of the target lysine.

References

  1. Pickart, C.M. Annu. Rev. Biochem. 70, 503–533 (2001).

    Article  CAS  Google Scholar 

  2. Johnson, E.S. Annu. Rev. Biochem. 73, 355–382 (2004).

    Article  CAS  Google Scholar 

  3. Hershko, A. & Ciechanover, A. Annu. Rev. Biochem. 67, 425–479 (1998).

    Article  CAS  Google Scholar 

  4. Hochstrasser, M. Cell 107, 5–8 (2001).

    Article  CAS  Google Scholar 

  5. Jackson, P.K. et al. Trends Cell Biol. 10, 429–439 (2000).

    Article  CAS  Google Scholar 

  6. Ardley, H.C. & Robinson, P.A. Essays Biochem. 41, 15–30 (2005).

    Article  CAS  Google Scholar 

  7. Reverter, D. & Lima, C.D. Nature 435, 687–692 (2005).

    Article  CAS  Google Scholar 

  8. Zheng, N., Wang, P., Jeffrey, P.D. & Pavletich, N.P. Cell 102, 533–539 (2000).

    Article  CAS  Google Scholar 

  9. Zhang, M. et al. Mol. Cell 20, 525–538 (2005).

    Article  CAS  Google Scholar 

  10. Bernier-Villamor, V., Sampson, D.A., Matunis, M.J. & Lima, C.D. Cell 108, 345–356 (2002).

    Article  CAS  Google Scholar 

  11. Wu, P.Y. et al. EMBO J. 22, 5241–5250 (2003).

    Article  CAS  Google Scholar 

  12. Yunus, A.A. & Lima, C.D. Nat. Struct. Mol. Biol. 13, 491–499 (2006).

    Article  CAS  Google Scholar 

  13. Sarcevic, B., Mawson, A., Baker, R.T. & Sutherland, R.L. EMBO J. 21, 2009–2018 (2002).

    Article  CAS  Google Scholar 

  14. Mahajan, R., Delphin, C., Guan, T., Gerace, L. & Melchior, F. Cell 88, 97–107 (1997).

    Article  CAS  Google Scholar 

  15. Pichler, A., Gast, A., Seeler, J.S., Dejean, A. & Melchior, F. Cell 108, 109–120 (2002).

    Article  CAS  Google Scholar 

  16. Pichler, A., Knipscheer, P., Saitoh, H., Sixma, T.K. & Melchior, F. Nat. Struct. Mol. Biol. 11, 984–991 (2004).

    Article  CAS  Google Scholar 

  17. Tolbert, B.S. et al. Biochemistry 44, 16385–16391 (2005)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knipscheer, P., Sixma, T. Divide and conquer: the E2 active site. Nat Struct Mol Biol 13, 474–476 (2006). https://doi.org/10.1038/nsmb0606-474

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb0606-474

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing