Molecular Mechanism of Action of Microtubule-Stabilizing Anticancer Agents

Taxane Mechanism of Action Kinesin
DOI: 10.1126/science.1230582 Publication Date: 2013-01-04T05:46:42Z
ABSTRACT
Microtubule-stabilizing agents (MSAs) are efficacious chemotherapeutic drugs widely used for the treatment of cancer. Despite importance MSAs medical applications and basic research, their molecular mechanisms action on tubulin microtubules remain elusive. We determined high-resolution crystal structures αβ-tubulin in complex with two unrelated MSAs, zampanolide epothilone A. Both compounds were bound to taxane pocket β-tubulin respective side chains induce structuring M-loop into a short helix. Because establishes lateral contacts microtubules, these findings explain how taxane-site promote microtubule assembly stability. Further, our results offer fundamental structural insights control dynamics.
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