Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
GoGreen Membership

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Sci. STKE, 31 May 2005
Vol. 2005, Issue 286, p. tw209
[DOI: 10.1126/stke.2862005tw209]

EDITORS' CHOICE

DRUG DESIGN The Devil Is in the Details

Protein phosphorylation is a major regulatory mechanism for control of many aspects of cellular function and is catalyzed by enzymes known as protein kinases. Modulation of the activity of protein kinases thus offers many opportunities for the development of therapeutically beneficial drugs. However, the catalytic domains of the protein kinases are very similar, so it has been a challenge to identify or design specific inhibitors. Cohen et al. (see the Perspective by Ahn and Resing) overcame this problem through careful analysis of the kinase catalytic sites and comparison of the known sequences of the nearly 500 human protein kinases. They combined two distinctive properties of the catalytic site of the RSK1 and RSK2 protein kinases in order to design small-molecule inhibitors that potently and selectively blocked activity of the RSK enzymes in vitro and in vivo.

M. S. Cohen, C. Zhang, K. M. Shokat, J. Taunton, Structural bioinformatics-based design of selective, irreversible kinase inhibitors. Science 308, 1318-1321 (2005). [Abstract] [Full Text]

N. G. Ahn, K. A. Resing, Lessons in rational drug design for protein kinases. Science 308, 1266-1267 (2005). [Summary] [Full Text]

Citation: The Devil Is in the Details. Sci. STKE 2005, tw209 (2005).

ADVERTISEMENT
Click Me!

ADVERTISEMENT

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)