Linear Free Energy Relationships for Enzymatic Reactions: Fresh Insight from a Venerable Probe.
Prof. John Richard
SUNY Distinguished Professor of Chemistry, University at Buffalo, USA
Linear free energy relationships (LFERs) for substituent effects on reactions that proceed through similar transition states provide insight into transition state structures. A classical approach to the analysis of LFERs showed that differences in the slopes of Brønsted correlations for addition of substituted alkyl alcohols to ring-substituted 1-phenylethyl carbocations and to the β-galactopyranosyl carbocation intermediate of reactions catalyzed by β-galactosidase provide evidence that the enzyme catalyst modifies the curvature of the energy surface at the saddle point for the transition state for nucleophile addition. We have worked to generalize the use of LFERs in the determination of enzyme mechanisms. The defining property of enzyme catalysts is their specificity for binding the transition state with a much higher affinity than the substrate.
A longer abstract, and an account of the work carried out in the RIchard laboratory, can be found here: https://pubs.acs.org/doi/10.1021/acs.accounts.1c00147
