The catalytic power of enzymes: conformational selection or transition state stabilization?

FEBS Letters
Jesús GiraldoJuan Serra

Abstract

The mechanism by which enzymes produce enormous rate enhancements in the reactions they catalyze remains unknown. Two viewpoints, selection of ground state conformations and stabilization of the transition state, are present in the literature in apparent opposition. To provide more insight into current discussion about enzyme efficiency, a two-state model of enzyme catalysis was developed. The model was designed to include both the pre-chemical (ground state conformations) and the chemical (transition state) components of the process for the substrate both in water and in the enzyme. Although the model is of general applicability, the chorismate to prephenate reaction catalyzed by chorismate mutase was chosen for illustrative purposes. The resulting kinetic equations show that the catalytic power of enzymes, quantified as the k(cat)/k(uncat) ratio, is the product of two terms: one including the equilibrium constants for the substrate conformational states and the other including the rate constants for the uncatalyzed and catalyzed chemical reactions. The model shows that these components are not mutually exclusive and can be simultaneously present in an enzymic system, being their relative contribution a property of the enzyme....Continue Reading

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Citations

Nov 26, 2008·Natural Product Reports·Marc W van der Kamp, Adrian J Mulholland
Dec 21, 2010·Biochemistry. Biokhimii︠a︡·O S FedorovaD G Knorre
Feb 20, 2007·Current Opinion in Chemical Biology·Hans Martin Senn, Walter Thiel
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Jan 29, 2009·Angewandte Chemie·Hans Martin Senn, Walter Thiel
Apr 15, 2020·Medicinal Research Reviews·Bharath SrinivasanJames Robinson
Dec 16, 2016·The Journal of Physical Chemistry. B·Esteban Vöhringer-Martinez, Ciro Dörner

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