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Novel and improved crystal structures of Haemophilus influenzae, E. coli and P. aeruginosa Penicillin-Binding-Protein 3 (PBP3) and N. gonorrhoeae PBP2: Towards a better understanding of β-lactam target-mediated resistance

DOI: 10.1016/j.jmb.2019.07.010 DOI Help

Authors: Dom Bellini (University of Warwick) , Lizbe Koekemoer (University of Cape Town; Structural Genomic Consortium, Oxford University) , Hector Newman (University of Warwick) , Christopher G. Dowson (University of Warwick)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Molecular Biology

State: Published (Approved)
Published: July 2019

Abstract: Even with the emergence of antibiotic resistance, penicillin and the wider family of beta-lactams have remained the single most important family of antibiotics. The periasmic/extracytoplasmic targets of penicillin are a family of enzymes with a highly conserved catalytic activity involved in the final stage of bacterial cell wall (peptidoglycan, PG) biosynthesis. Named after their ability to bind penicillin, rather than their catalytic activity these key targets are called penicillin-binding proteins (PBPs).Resistance is predominantly mediated by reducing the target drug concentration via beta-lactamases, however, naturally transformable bacteria have also acquired target mediated resistance by inter-species recombination. Here we focus on structural based interpretations of amino acid alterations associated with the emergence of resistance within clinical isolates and include new PBP3 structures along with new, and improved, PBP-beta-lactam co-structures.

Journal Keywords: Penicillin-resistance; Penicillin-binding-proteins; PBP3; Crystallography

Diamond Keywords: Bacteria

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Added On: 17/07/2019 09:54

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Antibiotic Resistance Infectious Diseases Pathogens Structural biology

Technical Tags:

Diffraction Macromolecular Crystallography (MX)