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An NMR investigation of the mechanism of action of uridine DNA glycosylase; a remarkably effective DNA repair system

Reference	B14739
Principal Investigator / Supervisor	Professor Michael Blackburn
Co-Investigators / Co-Supervisors	Professor Joseph Harrity, Professor Jon Waltho
Institution	University of Sheffield
Department	Chemistry
Funding type	Research
Value (£)	126,588
Status	Completed
Type	Research Grant
Start date	01/01/2001
End date	01/01/2003
Duration	24 months

Abstract

Based on X-ray studies on substrate and product complexes for uridine DNA glycohydrolase, UDG, we have proposed a mechanism involving major distortion of substrate to unite orthogonal stereoelectronic effects conducive to glycosylic bond cleavage. We now propose NMR studies on substrate and product complexes, using generally isotopically labelled protein and four selectively-labelled nucleotide substrates and analogues. These are designed to validate or falsify the proposed dissociative mechanism by (a) the location of critical hydrogen atoms in substrate and product, (b) definition of the nature and degree of distortion of substrate analogues in the active site, and (c) identification of key protein-substrate interactions.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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