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

Add time:08/17/2019    Source:sciencedirect.com

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.

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