A solution to the subdiffusion-efficiency paradox: Inactive states enhance reaction efficiency at subdiffusion conditions in living cells

TL;DR

This paper demonstrates that inactive states in enzymes can improve reaction efficiency under subdiffusive conditions typical in crowded cellular environments, challenging traditional views on diffusion limitations.

Contribution

It introduces a novel mechanism showing inactive enzyme states enhance reaction efficiency in subdiffusive cellular conditions, supported by modeling on percolation clusters.

Findings

Inactive enzyme states prevent non-specific binding

Reduced non-specific binding improves enzyme efficiency

Subdiffusion can be advantageous for enzyme activity in cells

Abstract

Macromolecular crowding in living biological cells effects subdiffusion of larger biomolecules such as proteins and enzymes. Mimicking this subdiffusion in terms of random walks on a critical percolation cluster, we here present a case study of EcoRV restriction enzymes involved in vital cellular defence. We show that due to its so far elusive propensity to an inactive state the enzyme avoids non-specific binding and remains well-distributed in the bulk cytoplasm of the cell. Despite the reduced volume exploration capability of subdiffusion processes, this mechanism guarantees a high efficiency of the enzyme. By variation of the non-specific binding constant and the bond occupation probability on the percolation network, we demonstrate that reduced non-specific binding are beneficial for efficient subdiffusive enzyme activity even in relatively small bacteria cells. Our results corroborate a more local picture of cellular regulation.