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Substrate analogues for Fen-1 Mre-11 and RNaseH II enabling mechanistic enzymology biophysical and structural studies

Reference	B19316
Principal Investigator / Supervisor	Professor Jane Grasby
Co-Investigators / Co-Supervisors	Professor Richard Cosstick
Institution	University of Sheffield
Department	Chemistry
Funding type	Research
Value (£)	192,736
Status	Completed
Type	Research Grant
Start date	01/02/2004
End date	31/01/2007
Duration	36 months

Abstract

Fen-1, Mre 11 and RNASE H II are metalloenzymes that play critical roles in DNA replication and repair. They all catalyse the hydrolysis of nucleic acid substrates to generate products with 5 - phosphate and 3 -hydroxyl termini respectively. Substrate analogues will be generated, where the leaving group oxygen will be replaced with S,NH or CH2. The resultant oligomers will be tested as substrates for the enzymes and if substrates will be exploited to probe the mechanism of the enzymes. The properties of non-cleavable substrate analogues will be thoroughly investigated and then exploited in biophysical studies of the ternary (enzyme-substrate analogue-metal ion) complexes. The substrate analogues will be supplied to the Tainer lab for crystallisation trials to enable co-crystal structures of these important enzymes to be obtained.

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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