Conformation-changing enzymes and macromolecular crowding.

Tomasz Skóra,Svyatoslav Kondrat,Mihail N Popescu

doi:10.1039/d0cp06631a

Abstract

We study how crowding affects the activity and catalysis-enhanced diffusion of enzymes and passive tracers by employing a fluctuating-dumbbell model of conformation-changing enzymes. Our Brownian dynamics simulations reveal that the diffusion of enzymes depends qualitatively on the type of crowding. If only enzymes are present in the system, the catalysis-induced enhancement of the enzyme diffusion - somewhat counter-intuitively - increases with crowding, while it decreases if crowding is due to inert particles. For the tracers, the diffusion enhancement increases with increasing the enzyme concentration. We also show how the enzyme activity is reduced by crowding and propose a simple expression to describe this reduction. Our results highlight subtle effects at play concerning enzymatic activity and macromolecular transport in crowded systems, such as, e.g., the interior of living cells.

Highlights

We study how crowding affects the activity and catalysis-enhanced diffusion of enzymes and passive tracers by employing a fluctuatingdumbbell model of conformation-changing enzymes
Our Brownian dynamics simulations reveal that the diffusion of enzymes depends qualitatively on the type of crowding
If only enzymes are present in the system, the catalysis-induced enhancement of the enzyme diffusion – somewhat counter-intuitively – increases with crowding, while it decreases if crowding is due to inert particles

Summary

Introduction

We study how crowding affects the activity and catalysis-enhanced diffusion of enzymes and passive tracers by employing a fluctuatingdumbbell model of conformation-changing enzymes. Since an enzyme in the closed state cannot bind a substrate, the results in Fig. 2b and c imply that crowding reduces the enzyme’s catalytic activity.

Results

Conclusion