Reference: Li J, et al. (1996) Site-directed mutagenesis of Saccharomyces cerevisiae beta-tubulin: interaction between residue 167 and benzimidazole compounds. FEBS Lett 385(1-2):7-10

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Abstract

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

Reference Type
Journal Article | Research Support, U.S. Gov't, P.H.S.
Authors
Li J, Katiyar SK, Edlind TD
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