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Possible binding site for paclitaxel at microtubule pores
Author(s) -
Magnani Matteo,
Maccari Giorgio,
Andreu José M.,
Díaz J. F.,
Botta Maurizio
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.06994.x
Subject(s) - microtubule , paclitaxel , tubulin , binding site , biophysics , chemistry , microbiology and biotechnology , biology , biochemistry , cancer , genetics
Taxanes and other microtubule‐stabilizing agents comprise an important class of anticancer drugs. It is well known that taxanes act by binding to β‐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 β‐tubulin can form a suitable pocket on the outer microtubule surface, and that paclitaxel can efficaciously interact with this newly‐proposed binding site.