Chakrabarti, Gopal ; Sengupta, Suparna ; Bhattacharyya, Bhabatarak (1996) Thermodynamics of colchicinoid-tubulin interactions. Role of B-ring and C-7 substituent Journal of Biological Chemistry, 271 (6). pp. 2897-2901. ISSN 0021-9258
![]()
|
PDF
- Publisher Version
143kB |
Official URL: http://www.jbc.org/content/271/6/2897.abstract?sid...
Abstract
The quenching of tryptophan fluorescence has been used to determine the kinetic and thermodynamic parameters of binding of B-ring analogs of colchicine to tubulin. The on rate, activation energy, off-rate, and thermodynamics of binding reaction have been found to be controlled at different points of analog structure. The on-rate and off-rate of deacetamidocolchicine (DAAC) binding with tubulin is 17 times slower than that of 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone-tubulin (AC-tubulin) interaction, although both reactions have very similar activation energies. The presence of B-ring alone does not significantly affect the thermodynamics of the binding reactions either, since both AC-tubulin and DAAC-tubulin interactions are enthalpy driven. Introduction of a NH2 group at C-7 position of the B-ring, as in deacetylcolchicine (NH2-DAAC) lowers the on-rate further with a significant rise in the value of the activation energy. However, bulkier substitutions at the same position, as in demecolcine (NHMe-DAAC) and N-methyldemecolcine (NMe2-DAAC) have no significant additional effect either on the on-rate or on the value of activation energy. Introduction of NH2 group in the C-7 position of B-ring also increases the positive entropy of the binding reaction to a significant extent, and it is maximum when NMe2 is substituted instead of NH2 group. Thus, interaction of NH2-DAAC, NHMe-DAAC, and NMe2-DAAC with tubulin are entropy driven. Our results suggest that the B-ring side chain of aminocolchicinoids makes contact(s) with dimeric tubulin molecules.
Item Type: | Article |
---|---|
Source: | Copyright of this article belongs to American Society for Biochemistry and Molecular Biology. |
ID Code: | 26237 |
Deposited On: | 06 Dec 2010 12:52 |
Last Modified: | 17 May 2016 09:33 |
Repository Staff Only: item control page