Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm

Jinglin Fu, Yuhe Renee Yang, Alexander Johnson-Buck, Minghui Liu, Yan Liu, Nils G. Walter, Neal W. Woodbury, Hao Yan

Research output: Contribution to journalArticle

218 Citations (Scopus)

Abstract

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein-DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity.

Original languageEnglish
Pages (from-to)531-536
Number of pages6
JournalNature nanotechnology
Volume9
Issue number7
DOIs
Publication statusPublished - Jul 2014

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ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

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