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PNCC General Access - Structure-based antibiotic discovery on the bacterial membrane – Penicillin-binding proteins (PBPs)


EMSL Project ID
51300

Abstract

Our vision is to develop and use structural biology methods to characterize membrane-associated protein assemblies relevant to antibiotic resistance and bacterial pathogenicity. We aim to illuminate the mechanism and specificity of these targets and exploit this information in the design of novel antibiotics to control and prevent drug resistant bacterial infections. For the purposes of this request, we focus on the structural characterization of penicillin-binding proteins, commonly known as PBPs. These PBPs are excellent drug targets, with the well-known beta-lactam antibiotics inhibiting their transpeptidase activity. Despite the wealth of knowledge on the inhibition of the transpeptidase activity of these proteins, there is a lack of knowledge on the function and inhibition of the glycosyltransferase activity they exhibit. We propose to use cryo-EM to determine the structures of various PBPs in various states to provide a key foundation for the further development of antibacterial agents that can target these key enzymes

Project Details

Start Date
2020-03-15
End Date
2021-03-17
Status
Closed

Team

Principal Investigator

Natalie Strynadka
Institution
The University of British Columbia

Team Members

Craig Robb
Institution
The University of British Columbia

Liam Worrall
Institution
The University of British Columbia

Nathanael Caveney
Institution
The University of British Columbia

Harry Scott
Institution
Oregon Health & Science University