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Details of Grant 

EPSRC Reference: EP/V048988/1
Title: Shining Light on Metalloprotein Mechanism: Single Protein Crystal Catalytic Studies Driven by 'Caged' Electron Sources
Principal Investigator: Ash, Dr PA
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: University of Leicester
Scheme: Standard Research - NR1
Starts: 01 January 2021 Ends: 31 December 2022 Value (£): 186,373
EPSRC Research Topic Classifications:
Analytical Science Biophysics
Chemical Biology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
Early reviews of time-resolved crystallography identified the need for generalised ways of triggering reactivity. Roughly 30-50% of proteins are redox proteins, one third of all proteins contain a redox-active metal, and approximately 22% of submissions to the PDB contain a transition metal, so new methods that enable time-resolved study of redox reactions using sub-turnover techniques will have significant academic impact. Pulse radiolysis or X-ray photoreduction are not generally for protein studies, causing primary and secondary radiation damage and leading to structural ambiguity in reduced states. The methods proposed here use lower energy triggers; we anticipate future use of longer wavelength chromophores, further minimising risk of photodamage.

The ambitious technical developments in this proposal have the potential to revolutionise biophysical capabilities, enabling studies of redox protein mechanism in exquisite chemical and structural detail. Combining single crystal spectroscopy, electrochemical control, and synchronous reaction initiation using a 'photo-caged' electron source we will build a platform technology with potentially transformative impact on biophysics and structural biology, and provide unprecedented possibilities to exploit time-resolved crystallographic and spectroscopic methods at national and international facilities. Thus far these methods have been largely inaccessible to 'real time' studies of redox proteins, as generalised methods to synchronise redox reactivity in the crystalline state do not exist. The methodology developed here overcomes the challenges of rapid triggering of electrochemical reactions in crystallo, whilst simultaneously allowing in situ infrared spectroscopic monitoring of transient redox species to characterise electrocatalytic reactions on sub-turnover timescales. This cutting-edge enabling technology will allow studies of previously inaccessible catalytic intermediates, driving scientific progress in biophysics, chemical and structural biology, and establishing the UK at the forefront of these unique and exciting scientific developments.
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Organisation Website: http://www.le.ac.uk