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Measurement and Optimization of the Redox Properties of Enzymes Using Single-Molecule Imaging, Controlled Electrochemical Potential, and Nanoscale Confinement


EMSL Project ID
25669

Abstract

We propose a new multi-disciplinary approach to single-molecule spectroscopy to image the redox kinetics of enzymes in spatially confined geometries under controlled electrochemical potential. We will use selective nanoscale confinement to reduce the set of conformations available to the enzyme and measure the effects of reduced conformational freedom on reaction rates. Selective, site-directed mutations will permit controlled tagging and tethering of the same target enzymes leading to new understanding of the relationships between rate constant fluctuations (dynamic disorder) and the degrees of freedom of the active site and surrounding enzyme structures. Cyclic voltammetry will be coupled to single-molecule spectroscopy to measure rapid conformational shifts as a function of chemical potential. The results with enzymes involved in electron transfer reactions will enable a deeper understanding of the fundamental factors controlling the rapid conformational changes affecting turnover rate required for enzymatic activity versus those that merely inhibit reactivity by allowing the enzyme to randomly explore unreactive configurations. The knowledge developed using these techniques will ultimately enable the successful integration of optimized enzymatic activity in composite materials without including the entire native enzyme molecule. This will create a new dimension of materials suitable to address problems in fuel cells, hydrogen production, displays, and lighting.

Project Details

Project type
Large-Scale EMSL Research
Start Date
2007-05-29
End Date
2009-09-30
Status
Closed

Team

Principal Investigator

Thomas Squier
Institution
Western University of Health Sciences

Team Members

Chenghong Lei
Institution
Guilin University of Technology

Eric Ackerman
Institution
Sandia National Laboratory

Dehong Hu
Institution
Environmental Molecular Sciences Laboratory

Charles Windisch
Institution
Pacific Northwest National Laboratory

Related Publications

C Lei, D Hu, E Ackerman: Clay Nanoparticle-Supported Single-Molecule Fluorescence Spectroelectrochemistry. Nano Letters 9 (2009) 655-58.
Hu D, and G Orr. 2010. "Nanometer Resolution Imaging by Single Molecule Switching." Nano Reviews 1:5122. doi:10.3402/nano.v1i0.5122
Lei C, D Hu, and EJ Ackerman. 2008. "Single-molecule Fluorescence Spectroelectrochemistry of Cresyl Violet." Chemical Communications (43):5490-5492. doi:10.1039/b812161c