| Autor: |
Entwistle RA; Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045-7534, USA., Winefield RD, Foland TB, Lushington GH, Himes RH |
| Jazyk: |
angličtina |
| Zdroj: |
FEBS letters [FEBS Lett] 2008 Jul 09; Vol. 582 (16), pp. 2467-70. Date of Electronic Publication: 2008 Jun 18. |
| DOI: |
10.1016/j.febslet.2008.06.013 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Plný text