Hydrogen bonding in enzymatic catalysis: Analysis of energetic contributions

Abstract

Enzymes typically form hydrogen bonds with substrate moieties that undergo electronic rearrangement in the course of reaction. This article reviews results that suggest that these hydrogen bonds can be strengthened in the transition state to a greater extent within the context of the enzymatic active site than in aqueous solution. Comparisons in model systems demonstrate this differential strengthening effect and suggest that it may provide substantial rate enhancements for enzymatic reactions relative to solution reactions. Despite their likely importance, quantitative dissection of the role of these "reaction center" hydrogen bonds in enzymatic catalysis is blurred because the energetic contributions of these hydrogen bonds are intertwined with those of hydrogen bonds and other interactions that fold the enzyme and position the bound substrate. This interconnection between binding interactions and rate enhancement is a fundamental property of enzymatic catalysis.