Targeting bacterial membrane sensory proteins for future drug discovery

ITQB Seminar

Title: Targeting bacterial membrane sensory proteins for future drug  discovery:expression, purification and in vitro activities of the genome complement of  intact membrane sensor kinases of Enterococcus faecalis V583

Speaker: Mary K. Phillips-Jones

Affiliation: Institute of Molecular & Cellular Biology, University of Leeds,UK

Host: Margarida Archer, Head of Membrane Protein Crystallography Laboratory

Abstract:

Enterococci are significant agents of nosocomial infection. Of particular concern is their increasing resistance to antibiotic treatments and there is an urgent need to identify new therapies to combat these infections.
Two-component signal transduction systems are the main mechanism by which bacteria, including enterococci, sense and respond to their environment, and their membrane-located histidine protein kinases (HPKs) generally
 constitute the sensory components of these systems. HPK sensory proteins constitute good targets for new antibacterial agents, particularly as new therapies may not need to cross the membrane barrier to access their target sites of
  inhibition. However, relatively little is known about the structures of intact HPK proteins, their fundamental mechanisms or indeed the precise nature of the molecular signals sensed by these membrane proteins, because of the technical challenges of producing sufficient quantities of these hydrophobic membrane proteins. In this presentation, I describe our
  evaluation of an approach for the heterologous production, purification and activities of the sixteen intact membrane sensor kinases of Enterococcus faecalis. Identification of molecular signals that modulate the
 activities of some of these sensors is also described, particularly with respect to the FsrC, VicK and VanS sensors, together with recent structural studies undertaken to study ligand- and inhibitor-protein interactions.