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]
- 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 YesInhibitorDetails Mebendazole Tubulin beta-4B chain Protein Humans YesInhibitorDetails