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Structure and function of sterol demethylases from Mycobacterium tuberculosis and Streptomyces coelicolor
Reference
C15314
Principal Investigator / Supervisor
Professor Andrew Munro
Co-Investigators /
Co-Supervisors
Dr Iain Hunter
Institution
University of Leicester
Department
Biochemistry
Funding type
Research
Value (£)
147,392
Status
Completed
Type
Research Grant
Start date
01/10/2001
End date
30/09/2004
Duration
36 months
Abstract
The sterol demethylase P450s from Mycobacterium tuberculosis and Streptomyces coelicolor are soluble, unlike their membrane-bound eukaryotic counterparts; the lanosterol demethylases. Fungal demethylases are targets for azole anti-fungals, but there is no structural rationale for the drugs' potency (e.g. fluxconazole), since no atomic structures have been solved. We have expressed/purified/crystallised the M. tuberculosis P450, and cloned the Streptomyces P450. We will express redox partners for the M. tuberculosis P450, determine kinetic and spectroscopic characteristics, and solve the P450 structure. We will express/purify the Streptomyces P450 and analyse function in a knockout strain. The outcome will be the first structural data for a sterol demethylase, as well as elucidation of functional and kinetic properties.
Summary
unavailable
Committee
Closed Committee - Biochemistry & Cell Biology (BCB)
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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