Fluctuations of Electric Fields in the Active Site of the Enzyme Ketosteroid Isomerase

TL;DR

This study investigates how conformational dynamics in Ketosteroid Isomerase influence electric field fluctuations in its active site, revealing that protein motions outside the active site help stabilize electric fields relevant to catalysis.

Contribution

It demonstrates that enzyme dynamics outside the active site modulate electric fields, offering insights for designing synthetic enzymes that leverage electric field fluctuations.

Findings

Protein motions outside the active site stabilize electric fields.

Electric field fluctuations are influenced by cooperative side chain motions.

Dynamic stabilization occurs at different timescales.

Abstract

We report the effect of conformational dynamics on the fluctuations of electric fields in the active site of the enzyme Ketosteroid Isomerase (KSI). While KSI is considered rigid with little conformational variation to support different stages of the catalytic cycle, we show that KSI utilizes cooperative side chain motions of the entire protein scaffold outside the active site, which contribute negligibly to the electric fields on the substrate, by progressively stabilizing electric field contributions by particular active site residues at different timescales. The design of synthetic enzymes could benefit from strategies that can take advantage of the dynamics by using electric fields fluctuations as a guide.