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Live Imaging to Study Microtubule Dynamic Instability in Taxane-resistant Breast Cancers
Published on: February 20, 2017
Possible binding site for paclitaxel at microtubule pores
Matteo Magnani1, Giorgio Maccari, José M Andreu
1Department of Pharmaceutical and Chemical Technology, Faculty of Pharmacy, University of Siena, Italy.
Abstract:
Taxanes and other microtubule-stabilizing agents comprise an important class of anticancer drugs. It is well known that taxanes act by binding to beta-tubulin on the lumenal side of microtubules. However, experimental evidence obtained in recent years led to the hypothesis of an external site on the microtubule wall to which taxanes and other microtubule-stabilizing agents could bind before being internalized to their lumenal site. In the present study, different computational techniques were combined to explore the possible existence of an exposed and easily accessible binding site for microtubule-stabilizing agents on the outside of microtubules. The results obtained indicate that the conformational rearrangement of the H6-H7 hoop of beta-tubulin can form a suitable pocket on the outer microtubule surface, and that paclitaxel can efficaciously interact with this newly-proposed binding site.
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