Related Experiment Video
Updated: Jul 17, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Contributions of conformational compression and preferential transition state stabilization to the rate enhancement
Cristiano Ruch Werneck Guimarães1, Matthew P Repasky, Jayaraman Chandrasekhar
1Department of Chemistry, Yale University, 225 Prospect Street, New Haven, Connecticut 06520-8107, USA.
Abstract:
The rate enhancement provided by the chorismate mutase (CM) enzyme for the Claisen rearrangement of chorismate to prephenate has been investigated by application of the concept of near attack conformations (NACs). Using a combined QM/MM Monte Carlo/free-energy perturbation (MC/FEP) method, 82% and 100% of chorismate conformers were found to be NAC structures in water and in the CM active site, respectively. Consequently, the conversion of non-NACs to NACs does not contribute to the free energy of activation from preorganization of the substrate into NACs. The FEP calculations yielded differences in free energies of activation that well reproduce the experimental data. Additional calculations indicate that the rate enhancement by CM over the aqueous phase results primarily from conformational compression of NACs by the enzyme and that this process is enthalpically controlled. This suggests that preferential stabilization of the transition state in the enzyme environment relative to water plays a secondary role in the catalysis by CM.
More Related Videos
Related Concept Videos
Induced-fit Model
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical characteristics of...
Allosteric Regulation
Mechanisms of Membrane-bending
Membrane bending can happen due to intrinsic changes in lipid composition or extrinsic association with different proteins. The proteins involved...
SN2 Reaction: Transition State
When the nucleophile approaches the electrophilic carbon with its lone pairs, the halide acts as a leaving group and moves away with the electron-pair bonded to the carbon. Dotted partial bonds represent the bonds being formed or broken...
Introduction to Mechanisms of Enzyme Catalysis
Transition State Theory

