Benzimidazole binding to Haemonchus contortus tubulin: a question of structure.

Abstract

The September 2001 issue of Trends in Parasitology had a review entitled `Genetic variability following selection of Haemonchus contortus with anthelmintics¿, by Roger K. Prichard [1]. This included a diagrammatic representation of the proposed benzimidazole (BZM) binding to H. contortus tubulin, presumably based on the electron diffraction structure of porcine tubulin ?-chain [2], although this was not stated. It was suggested that BZM dock with the tubulin molecule within a site formed by four residues on the tubulin ?-chain (Ser166, Phe167, Phe200 and Cys201). We concur that these four ?-tubulin residues cluster together in the published model of the three-dimensional conformation of the protein; however, using this structure, we find the proposed BZM docking to be questionable on the following grounds.