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.

Chemical biology

Caught in the activation

Nature volume 461, pages 484–485 (2009)Cite this article

A crystal structure reveals how a protein kinase is activated by the binding of a small molecule at a pocket far from the catalytic site. This opens the door to the design of modulators of protein phosphorylation.

The protein functions that regulate cell behaviour are themselves tightly regulated by many different inputs. One of these is phosphorylation, the process in which a phosphate group from an ATP molecule is attached to a protein by a protein kinase enzyme1. There is considerable interest in identifying small molecules that can modulate protein kinase activity, both as research tools and as potential human therapeutic agents. Indeed, eleven kinase inhibitors are already used as drugs for treating cancer, and several more are in clinical trials for the treatment of immune and inflammatory diseases2.

Your institute does not have access to this article

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Small-molecule activation of PDK1.

References

  1. Pawson, T. & Scott, J. D. Trends Biochem. Sci. 30, 286–290 (2005).

    CAS  Article  Google Scholar 

  2. Zhang, J., Yang, P. L. & Gray, N. S. Nature Rev. Cancer 9, 28–39 (2009).

    Article  Google Scholar 

  3. Engel, M. et al. EMBO J. 25, 5469–5480 (2006).

    CAS  Article  Google Scholar 

  4. Hindie, V. et al. Nature Chem. Biol. 5, 758–764 (2009).

    CAS  Article  Google Scholar 

  5. Huse, M. & Kuriyan, J. Cell 109, 275–282 (2002).

    CAS  Article  Google Scholar 

  6. Pellicena, P. & Kuriyan, J. Curr. Opin. Struct. Biol. 16, 702–709 (2006).

    CAS  Article  Google Scholar 

  7. Biondi, R. M. et al. EMBO J. 19, 979–988 (2000).

    CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Yi Liu is in the Department of Research and Development, Intellikine, Inc., 10931 North Torrey Pines Road, La Jolla, California 92037, USA. yi@intellikine.com,

    Yi Liu

Authors
  1. Yi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Liu, Y. Caught in the activation. Nature 461, 484–485 (2009). https://doi.org/10.1038/461484a

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/461484a

Search

Advanced 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