Title

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

Date of Original Version

2-13-2013

Type

Article

PubMed ID

23305346

Abstract or Description

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.

DOI

10.1021/ja310377d

 

Published In

Journal of the American Chemical Society, 135, 6, 2263-2272.