Biophysical Journal 70: 174-181 (1996)
© 1996 the Biophysical Society

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Di Cera, E Articles by Dang, Q D Search for Related Content PubMed PubMed Citation Articles by Di Cera, E Articles by Dang, Q D

Theory of allosteric effects in serine proteases.

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA. enrico@caesar.wustl.edu

ABSTRACT

The classical Botts-Morales theory for the action of a modifier on the catalytic properties of an enzyme has been extended to deal with allosteric effects in serine proteases. The exact analytical solution derived for the linkage scheme at steady state provides a rigorous framework for the study of many biologically relevant systems, including enzymes activated by monovalent cations and cofactor-controlled protease-zymogen interactions in blood coagulation. When the enzyme obeys Michaelis-Menten kinetics, the exact solution of the kinetic linkage scheme simplifies considerably. Of particular importance for practical applications is a simple equation expressing the dependence of the specificity constant of the enzyme, kcat/Km, on the concentration of the modifier, from which the equilibrium binding constant for the formation of the enzyme-modifier complex can be estimated. Analysis of the allosteric changes in thrombin activity induced by thrombomodulin and Na+ in terms of this equation yields accurate determinations of the equilibrium binding constants for both effectors.

This article has been cited by other articles:

				L. A. Bush, R. W. Nelson, and E. Di Cera Murine Thrombin Lacks Na+ Activation but Retains High Catalytic Activity J. Biol. Chem., March 17, 2006; 281(11): 7183 - 7188. [Abstract] [Full Text] [PDF]

				H. Xu, L. A. Bush, A. O. Pineda, S. Caccia, and E. Di Cera Thrombomodulin Changes the Molecular Surface of Interaction and the Rate of Complex Formation between Thrombin and Protein C J. Biol. Chem., March 4, 2005; 280(9): 7956 - 7961. [Abstract] [Full Text] [PDF]

				A. O. Pineda, C. J. Carrell, L. A. Bush, S. Prasad, S. Caccia, Z.-W. Chen, F. S. Mathews, and E. Di Cera Molecular Dissection of Na+ Binding to Thrombin J. Biol. Chem., July 23, 2004; 279(30): 31842 - 31853. [Abstract] [Full Text] [PDF]

				S. Prasad, A. M. Cantwell, L. A. Bush, P. Shih, H. Xu, and E. Di Cera Residue Asp-189 Controls both Substrate Binding and the Monovalent Cation Specificity of Thrombin J. Biol. Chem., March 12, 2004; 279(11): 10103 - 10108. [Abstract] [Full Text] [PDF]

				G. B. Birrell, T. O. Zaikova, A. V. Rukavishnikov, J. F. W. Keana, and O. H. Griffith Allosteric Interactions within Subsites of a Monomeric Enzyme: Kinetics of Fluorogenic Substrates of PI-Specific Phospholipase C Biophys. J., May 1, 2003; 84(5): 3264 - 3275. [Abstract] [Full Text] [PDF]