Site-directed mutagenesis of Saccharomyces cerevisiae β-tubulin: interaction between residue 167 and benzimidazole compounds

摘要: Benzimidazoles are widely used as anthelmintic agents and systemic fungicides. In susceptible organisms, benzimidazoles bind to β-tubulin block microtubule polymerization. To further characterize this interaction, site-directed mutagenesis followed by gene replacement was change Saccharomyces cerevisiae residue Phe-167 Tyr. Consistent with previous studies, mutation resulted in at least 3–4-fold decreased sensitivity the benzimidazole derivatives carbendazim nocodazole. The Tyr-167 mutant cold sensitive, implying a direct effect on binding rather than nonspecific increase stability. Surprisingly, had 8-fold increased derivative benomyl, which is structurally identical except position 1. This suggests that 167 interacts vicinity of 1-position.