Assessment of benzimidazole binding to individual recombinant tubulin isotypes from Haemonchus contortus.

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Oxberry ME, Gear TG, Prichard RK

Assessment of benzimidazole binding to individual recombinant tubulin isotypes from Haemonchus contortus.

Parasitology. 2001 Jun;122(Pt 6):683-7.

PubMed ID

11444621 [ View in PubMed

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Abstract

One a- and 2 beta-tubulin isotypes (isotypes 1 and 2) from the parasitic nematode Haemonchus contortus were artificially expressed in E. coli and purified to obtain tubulin that was capable of polymerizing into microtubules. Binding of [14C] mebendazole (MBZ), a benzimidazole compound, to each individual unpolymerized isotype and to microtubules polymerized from recombinant alpha- and beta-tubulin was assessed and Kd and Bmax values determined. Mebendazole bound to the individual tubulin isotypes with a stoichiometry of 1:1. Binding occurred with highest affinity to alpha-tubulin followed by beta-tubulin isotype 2 and beta-tubulin isotype 1 indicating that alpha-tubulin may play a role in benzimidazole binding to microtubules. Upon polymerization of alpha- and beta-tubulin isotype 2 into microtubules the stoichiometry of binding increased to 2:1 (mebendazole : tubulin) while binding affinity remained the same. Mebendazole binding to alpha/beta-isotype 1 microtubules remained unchanged following polymerization. The increase in the number of benzimidazole receptors on alpha/beta-isotype 2 microtubules suggests the formation of a new benzimidazole receptor upon polymerization.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mebendazole	Tubulin alpha-1A chain	Protein	Humans	Yes	Inhibitor	Details
Mebendazole	Tubulin beta-4B chain	Protein	Humans	Yes	Inhibitor	Details