Ulaganathan, V., Talapatra, S.K., Rath, O., Pannifer, A., Hackney, D.D. and Kozielski, F. (2013) Structural insights into a unique inhibitor binding pocket in kinesin spindle protein. Journal of the American Chemical Society, 135(6), pp. 2263-2272. (doi: 10.1021/ja310377d)
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Abstract
Human kinesin Eg5 is a target for drug development in cancer chemotherapy with compounds in phase II clinical trials. These agents bind to a well-characterized allosteric pocket involving the loop L5 region, a structural element in kinesin-5 family members thought to provide inhibitor specificity. Using X-ray crystallography, kinetic, and biophysical methods, we have identified and characterized a distinct allosteric pocket in Eg5 able to bind inhibitors with nanomolar Kd. This pocket is formed by key structural elements thought to be pivotal for force generation in kinesins and may represent a novel site for therapeutic intervention in this increasingly well-validated drug target.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Kozielski, Professor Frank and Talapatra, Mr Sandeep and Rath, Dr Oliver and Ulaganathan, Dr Venkat and Pannifer, Dr Andrew |
| Authors: | Ulaganathan, V., Talapatra, S.K., Rath, O., Pannifer, A., Hackney, D.D., and Kozielski, F. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Journal of the American Chemical Society |
| Publisher: | American Chemical Society |
| ISSN: | 0002-7863 |
| ISSN (Online): | 1520-5126 |
| Published Online: | 10 January 2013 |
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