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  • Title: The paclitaxel site in tubulin probed by site-directed mutagenesis of Saccharomyces cerevisiae beta-tubulin.
    Author: Entwistle RA, Winefield RD, Foland TB, Lushington GH, Himes RH.
    Journal: FEBS Lett; 2008 Jul 09; 582(16):2467-70. PubMed ID: 18570892.
    Abstract:
    Previously, we created a paclitaxel-sensitive strain of Saccharomyces cerevisiae by mutating five amino acid residues in beta-tubulin in a strain that has a decreased level of the ABC multidrug transporters. We have used site-directed mutagenesis to examine the relative importance of the five residues in determining sensitivity of this strain to paclitaxel. We found that the change at position 19 from K (brain beta-tubulin) to A (yeast beta-tubulin) and at position 227 from H (brain beta-tubulin) to N (yeast beta-tubulin) had no effect on the activity of paclitaxel. On the other hand, the changes V23T, D26G and F270Y, drastically reduced sensitivity of AD1-8-tax to paclitaxel. Molecular modeling and computational studies were used to explain the results.
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