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The molecular basis of halorespiration

Reference	BB/C00521X/1
Principal Investigator / Supervisor	Professor David Leys
Co-Investigators / Co-Supervisors
Institution	The University of Manchester
Department	Life Sciences
Funding type	Research
Value (£)	207,204
Status	Completed
Type	Research Grant
Start date	01/11/2005
End date	30/04/2009
Duration	42 months

Abstract

Halorespiration by anaerobic bacteria leads to low residual concentrations of the dehalogenated hydrocarbon at typically high dehalogenation rates. In view of these favourable degradation capacities halorespiring microorganisms have clear potential for bioremediation applications. This project aims to elucidate the molecular basis of halorespiration by studying both the transcriptional regulator CprK and the terminal reductase CprA, two key proteins in this process. CprK is a member of the widespread CPR-FNR family of HTH-transcriptional regulators. Our recent structure determination of CprK in complex with the effector ortho-chlorophenolacetic acid has revealed this protein to contain several novel features and presents a first and significant step to understanding this process. We propose to elucidate at the atomic level the mechanism by which OCPA binding induces the allosteric transition to the high-affinity DNA-binding form of CprK using both structural biology and biophysical studies on both wild-type and mutant forms of CprK. We will furthermore study both DNA-binding and RNA-polymerase binding events using similar techniques. We have also been able to purify the key enzyme CprA in mg quantities. The purified will be used for anaerobic crystallogenesis and structure determination of CprA. The knowledge gathered at the atomic level will enable further exploitation of halorespiring bacteria as dedicated degraders in biological remediation processes.

Summary

unavailable

Committee	Closed Committee - Biomolecular Sciences (BMS)
Research Topics	Industrial Biotechnology, Microbiology, Structural Biology
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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