Related Experiment Video
Updated: Jul 8, 2025

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Substrate Positioning Dynamics Involves a Non-Electrostatic Component to Mediate Catalysis
Yaoyukun Jiang1, Ning Ding1, Qianzhen Shao1
1Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
Abstract:
Substrate positioning dynamics (SPD) orients the substrate in the active site, thereby influencing catalytic efficiency. However, it remains unknown whether SPD effects originate primarily from electrostatic perturbation inside the enzyme or can independently mediate catalysis with a significant non-electrostatic component. In this work, we investigated how the non-electrostatic component of SPD affects transition state (TS) stabilization. Using high-throughput enzyme modeling, we selected Kemp eliminase variants with similar electrostatics inside the enzyme but significantly different SPD. The kinetic parameters of these mutants were experimentally characterized. We observed a valley-shaped, two-segment linear correlation between the TS stabilization free energy (converted from kinetic parameters) and substrate positioning index (a metric to quantify SPD). The energy varies by approximately 2 kcal/mol. Favorable SPD was observed for the distal mutant R154W, increasing the proportion of reactive conformations and leading to the lowest activation free energy. These results indicate the substantial contribution of the non-electrostatic component of SPD to enzyme catalytic efficiency.
More Related Videos
10:52Multiscale Sampling of a Heterogeneous Water/Metal Catalyst Interface using Density Functional Theory and Force-Field Molecular Dynamics
Published on: April 12, 2019
08:25Development of Heterogeneous Enantioselective Catalysts using Chiral Metal-Organic Frameworks MOFs
Published on: January 17, 2020
Related Concept Videos
Introduction to Mechanisms of Enzyme Catalysis
Enzymes
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
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...
Catalysis
Introduction to Enzymes
Most enzymes are proteins that speed up biochemical reactions without being consumed. Enzymes contain one or more active sites that...
Catalytically Perfect Enzymes
Most enzymes...