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The Interaction of Vincristine with Calf Brain Tubulin

Prakash, V. and Timasheff, S. N. (1983) The Interaction of Vincristine with Calf Brain Tubulin. Journal of Biological Chemistry, 258 (3). pp. 1689-1697.

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Abstract

The interaction of the antimitotic drug vincristine with tubulin has been investigated by the techniques of self-assembly, velocity sedimentation, fluorescence, circular dichroism, and differential spectroscopy. Vin- cristine has been shown to inhibit the self-assembly of tubulin into microtubules at substoichiometric concen- trations. The sedimentation velocity patterns at low vincristine concentration (<I X M to 7 X M) consist of a bimodal boundary with a 5.8 S peak and a fast moving peak, with a nominal sz0+ value of 9 S. The data conform to the ligand-promoted self-association theory of Cann and Goad (Cann, J. R., and Goad, W. B. (1972) Arch. Biochem. Biophys. 153,603-609). At higher vincristine concentrations ( 3 X M), most of the protein is polymerized and sediments as a hypersharp peak with a nominal sz0+ value of -20 S. The association constant for the binding of vincristine to tubulin, deter- mined by spectrofluorometry, is 3.5 X lo4 liters/mol at 25 “C. The binding of vincristine does not induce any significant conformational changes in tubulin; how- ever, the difference spectral results indicate perturba- tion of both vincristine and protein chromophores. tubulin at a rate much faster than that of colchicine binding,while Wilson (1970) has reported that high concentrations of VCR induce nearly complete stabilization of the tubulin-col-chicine binding activity. With the above findings in view, it seemed of interest to investigate the mechanism of binding of VCR to tubulin, the VCR-induced tubulin self-association, and the energetics of these interactions. The results of such a study are the subject of this paper. Preliminary reports of this work have been presented earlier (Prakash and Timasheff, 1980, a and b).

Item Type: Article
Uncontrolled Keywords: vincristine tubulin vinca alkaloids VCR-induced tubulin
Subjects: 500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 29 Protein Chemistry
500 Natural Sciences and Mathematics > 04 Chemistry and Allied Sciences > 02 Alkaloids Chemistry
Divisions: Protein Chemistry and Technology
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 08 Jan 2008 12:03
Last Modified: 29 Oct 2018 09:41
URI: http://ir.cftri.com/id/eprint/1613

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