Role of substrate unbinding in Michaelis–Menten enzymatic reactions

TLDR

Enzymes are essential biological catalysts, and single‑molecule spectroscopy now enables direct observation of their stochastic behavior during reactions. The study shows that, counterintuitively, faster unproductive substrate unbinding can accelerate product formation under specific conditions. The authors discuss the broad implications of this counterintuitive effect for enzymology.

Abstract

Significance Enzymes are biological catalysts vital to all life processes, and the quest to determine their inner workings continues to attract and fascinate scientists over a broad range of disciplines. With the advent of high-resolution methods of single-molecule spectroscopy, it is now possible to directly observe and manipulate the behavior of individual enzymes in the course of a chemical reaction. Chemistry at the single-molecule level is, however, inherently stochastic and, at times, extremely unintuitive. In this paper, we explain why, and under what circumstances, an increase in the rate at which an enzyme unproductively departs from a bound substrate will—unexpectedly—lead to an acceleration in the rate of product formation. The far-reaching implications of this effect are discussed.