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Molecular mechanism of drug transport by LmrA the bacterial homolog of the human multidrug resistance P-glycoprotein

ReferenceC15670
Principal Investigator / Supervisor Professor Hendrik Willem van Veen
Co-Investigators /
Co-Supervisors
Institution University of Cambridge
DepartmentPharmacology
Funding typeResearch
Value (£) 188,496
StatusCompleted
TypeResearch Grant
Start date 12/11/2001
End date 12/11/2004
Duration36 months

Abstract

ATP-binding cassette transporters are associated with many human disease phenotypes including multidrug resistance, adrenoleukodystrophy and Tangier disease. Insight into the mechanism of ABC transporters is vital for our ability to develop new drugs which can alter or circumvent the activity of these proteins. Recent evidence suggests that LmrA, the bacterial homolog of P- glycoprotein, mediates multidrug transport from the membrane by a two-cylinder engine mechanism. LmrA harbors two drug binding sites on opposite sides of the membrane which are interconverted in an ATP-dependent fashion. The aim of this proposal is to further test this mechanism by studying the link between ATP binding/hydrolysis, and the interaction of drugs with LmrA.

Summary

unavailable
Committee Closed Committee - Biochemistry & Cell Biology (BCB)
Research TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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