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.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|