title: Multi-enzyme complexes on DNA scaffolds capable of substrate channelling with an artificial swinging arm.
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.
authors.affiliation: 1] Center for Molecular Design and Biomimicry, Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA [2] Center for Innovations in Medicine, Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA [3] [4].
authors.forename: Jinglin
authors.initials: J
authors.lastname: Fu
authors.affiliation: 1] Center for Molecular Design and Biomimicry, Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA [2] Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA [3].
authors.forename: Yuhe Renee
authors.initials: YR
authors.lastname: Yang
authors.affiliation: Single Molecule Analysis Group, Department of Chemistry, University of Michigan at Ann Arbor, Ann Arbor, Michigan 48109, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Johnson-Buck
authors.affiliation: 1] Center for Molecular Design and Biomimicry, Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA [2] Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Minghui
authors.initials: M
authors.lastname: Liu
authors.affiliation: 1] Center for Molecular Design and Biomimicry, Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA [2] Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Single Molecule Analysis Group, Department of Chemistry, University of Michigan at Ann Arbor, Ann Arbor, Michigan 48109, USA.
authors.forename: Nils G
authors.initials: NG
authors.lastname: Walter
authors.affiliation: 1] Center for Innovations in Medicine, Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA [2] Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Neal W
authors.initials: NW
authors.lastname: Woodbury
authors.affiliation: 1] Center for Molecular Design and Biomimicry, Biodesign Institute at Arizona State University, Tempe, Arizona 85287, USA [2] Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Yan
mesh_terms: D004247:DNA / Q000737:chemistry*; D009097:Multienzyme Complexes / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry*
chemical_list: D009097:Multienzyme Complexes; D004247:DNA; D010088:Oxidoreductases