Project summary
The BACPROBIO project aims to explore the structural facets and modulation/inhibition of essential bacterial PPIs, involved in the assembly and integrity maintenance of bacterial cell envelope. The complex multilayered bacterial cell membrane, with its unique and essential structural components, provides several specific targets for antibiotic drug development.
The targeted essential bacterial PPIs are:
i) YejM-LapB-FtsH-LpxC (PPI-1) protein network, controlling the lipopolysaccharide biosynthesis,
ii) LpoB-PBP1B (PPI-2) protein-protein interaction involved in the biosynthesis of the peptidoglycan cell wall,
iii) DprE1-DprE2 (PPI-3) protein complex essential for the biosynthesis of Mycobacterium tuberculosis cell wall components.
The project employs state of the art methodologies, such as fragment-based ligand discovery by X-ray crystallography and 19F-NMR techniques, high-throughput and virtual ligand screenings, for the discovery of hits targeting bacterial PPIs, followed by their in vitro/in vivo validation. The project will establish novel medicinal chemistry and structural enzymology/biochemistry research directions within BBU and will establish the first automatized protein crystallization lab at the national level.