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

2014; Nature Portfolio; Volume: 9; Issue: 7 Linguagem: Inglês

10.1038/nnano.2014.100

1748-3395

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

Molecular Junctions and Nanostructures

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. Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes1. 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 complex2,3,4. 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 precision5,6,7 and can also provide nanomechanical control8,9,10,11. Until now, protein–DNA assemblies12 have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components13,14,15,16 or by facilitating the interface between enzymes/cofactors and electrode surfaces17,18. 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.