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Selected Works of Mohan Gupta, Jr.
Article
Epothilone and Paclitaxel: Unexpected Differences in Promoting the Assembly and Stabilization of Yeast Microtubules
Biochemistry (2002)
  • Claudia J. Bode, University of Kansas
  • Mohan L. Gupta, Jr., University of Kansas
  • Emily A. Reiff, University of Kansas
  • Kathy A. Suprenant, University of Kansas
  • Gunda I. Georg, University of Kansas
  • Richard H. Himes, University of Kansas
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Abstract
Paclitaxel (Taxol) and the epothilones are antimitotic agents that promote the assembly of
mammalian tubulin and stabilization of microtubules. The epothilones competitively inhibit the binding
of paclitaxel to mammalian brain tubulin, suggesting that the two types of compounds share a common
binding site in tubulin, despite the lack of structural similarities. It is known that paclitaxel does not
stabilize microtubules formed in vitro from Saccharomyces cereVisiae tubulin; thus, it would be expected
that the epothilones would not affect yeast microtubules. However, we found that epothilone A and B do
stimulate the formation of microtubules from purified yeast tubulin. In addition, epothilone B severely
dampens the dynamics of yeast microtubules in vitro in a manner similar to the effect of paclitaxel on
mammalian microtubules. We used current models describing paclitaxel and epothilone binding to
mammalian â-tubulin to explain why paclitaxel apparently fails to bind to yeast tubulin. We propose that
three amino acid substitutions in the N-terminal region and at position 227 in yeast â-tubulin weaken the
interaction of the 3¢-benzamido group of paclitaxel with the protein. These results also indicate that
mutagenesis of yeast tubulin could help define the sites of interaction with paclitaxel and the epothilones.
Disciplines
Publication Date
2002
DOI
10.1021/bi0121611
Publisher Statement
Reprinted (adapted) with permission from Epothilone and Paclitaxel:  Unexpected Differences in Promoting the Assembly and Stabilization of Yeast Microtubules, Claudia J. Bode, Mohan L. Gupta, Jr., Emily A. Reiff, Kathy A. Suprenant, Gunda I. Georg, and Richard H. Hime, Biochemistry 2002 41 (12), 3870-3874, DOI: 10.1021/bi0121611 . Copyright 2002 American Chemical Society.
Citation Information
Claudia J. Bode, Mohan L. Gupta, Emily A. Reiff, Kathy A. Suprenant, et al.. "Epothilone and Paclitaxel: Unexpected Differences in Promoting the Assembly and Stabilization of Yeast Microtubules" Biochemistry Vol. 41 Iss. 12 (2002) p. 3870 - 3874
Available at: http://works.bepress.com/mohan-gupta/4/