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

Jesús Giraldo, David Roche, Xavier Rovira, Juan Serra

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

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 kcat/kuncat 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. The developed mathematical expressions reveal that the conformational and reaction components of the process perform differently for the translation of molecular efficiency (changes in energy levels) into observed enzymic efficiency (changes in kcat), being, in general, more productive the component involving the transition state. © 2006 Federation of European Biochemical Societies.
Original languageEnglish
Pages (from-to)2170-2177
JournalFEBS Letters
Volume580
Issue number9
DOIs
Publication statusPublished - 17 Apr 2006

Keywords

  • Chorismate mutase
  • Enzyme efficiency
  • Ground state destabilization
  • Kinetic models
  • Substrate conformational selection
  • Transition state stabilization

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