Award details

Elucidating enzyme mechanism and physiological role of a key P450 enzyme (CYP121) from mycobacterium tuberculosis

Reference	C19757
Principal Investigator / Supervisor	Professor Andrew Munro
Co-Investigators / Co-Supervisors	Professor David Leys, Professor Nigel Scrutton, Professor Michael Sutcliffe
Institution	University of Leicester
Department	Biochemistry
Funding type	Research
Value (£)	196,872
Status	Completed
Type	Research Grant
Start date	01/03/2004
End date	31/08/2005
Duration	18 months

Abstract

The structure of CYP121, a key cytochrome P450 enzyme in M. tuberculosis (Mtb), has been solved to 1 Angstrom at Leicester. We will capitalise on the UKs first P450 structure to establish physiological substrate and role, to reconstitute activity with the cloned reductase (FprA) and ferredoxin redox partners, and to address unresolved problems in P450 catalysis. These relate to proton delivery pathways and identification of catalytic intermediates that accumulate when proton relay is retarded. CYP121 is highly expressed in Mtb and production is regulated by cellular stresses. It is strongly inhibited by azole drugs, and their Kd values are paralleled by their efficiency as anti-mycobacterials. We will deconvulute the biology of this important pathogen P450 and analyse important structure/function questions that will advance our understanding of P450 mechanism.

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

Associated awards:

C19757/2 Elucidating enzyme mechanism and physiological role of a key P450 enzyme (CYP121) from mycobacterium tuberculosis

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