Engineering enzymatic cascades on nanoscale scaffolds

Scaffold proteins are involved in many enzyme cascades in signaling pathways and metabolic processes. The study of scaffolds occurring in biological systems advances at a rapid pace and recently developed engineered synthetic scaffolds enable the precise placement of components of an enzymatic cascade within nanometer distances. Recent experimental results demonstrate significantly increased throughput of enzymatic cascades as a result of the utilization of a scaffold, but our understanding of the mechanisms responsible for this increase is not complete. We discuss the physics of diffusive transport processes relevant for these unique reaction–diffusion systems.

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► Scaffold proteins play an important role in biological enzymatic cascades.
► Novel engineered scaffolds have allowed construction of artificial enzymatic cascades.
► Diffusive transport of substrate molecules and spatial constraints impact cascade kinetics and scaffold contribution.