File(s) stored somewhere else

Please note: Linked content is NOT stored on Carnegie Mellon University and we can't guarantee its availability, quality, security or accept any liability.

Structural insights into a unique inhibitor binding pocket in kinesin spindle protein.

journal contribution
posted on 13.02.2013, 00:00 by Venkatasubramanian Ulaganathan, Sandeep K. Talapatra, Oliver Rath, Andrew Pannifer, David HackneyDavid Hackney, Frank Kozielski

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 K(d). 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.