Role of B-ring of colchicine in its binding to Zn(II)-induced tubulinsheets.

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Date
1987-03
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Abstract
Colchicine-tubulin dimer complex, a potent inhibitor of normal microtubule assembly undergoes extensive self-assembly in the presence of 1 × 10–4 Μ zinc sulphate. Polymers assembled from colchicine-tubulin dimer complexes are sensitive to cold. Although colchicine can be accomodated within the polymeric structure, the drug cannot bind to tubulin subunits in the intact polymers. This is evidenced by the fact that (a) the colchicine binding activity of tubulin is lost when allowed to polymerize with zinc sulphate, (b) the loss in colchicine binding could be prevented by preincubation of tubulin with 1 × 10–3 Μ CaCl2 or 1 × 10–5 Μ vinblastine sulphate and finally (c) no loss in colchicine binding activity is found when tubulin is kept at a concentration far below the critical concentration for polymerization. Unlike colchicine, its B-ring analogues desacetamido colchicine (devoid of the B-ring subtituent) and 2-methoxy-5- (2’,3’,4’-trimethoxyphenyl) tropone (devoid of the B-ring) can bind to tubulin subunits in the intact polymers. Thus we conclude that the colchicine binding domain on the tubulin molecule is mostly (if not completely) exposed in the Zn(II)-induced polymers and the B-ring substituent plays a major role in determining the binding ability of a colchicine analogue to tubulin in the intact Zn(II)-induced sheets.
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Keywords
Colchicine-tubulin dimer complex, B-ring, tubulin sheets
Citation
Banerjee Asok, Maity Sankar N, Chaudhuri Sukla Ray, Bhattacharyya B. Role of B-ring of colchicine in its binding to Zn(II)-induced tubulinsheets. Journal of Biosciences. 1987 Mar; 11(1-4): 525-536.