Structure-based design and in-parallel synthesis of inhibitors of AmpC beta-lactamase.
Tondi, D., Powers, R.A., Caselli, E., Negri, M.C., Blazquez, J., Costi, M.P., Shoichet, B.K.(2001) Chem Biol 8: 593-611
- PubMed: 11410378 
- DOI: https://doi.org/10.1016/s1074-5521(01)00034-5
- Primary Citation of Related Structures:  
1GA9 - PubMed Abstract: 
Group I beta-lactamases are a major cause of antibiotic resistance to beta-lactams such as penicillins and cephalosporins. These enzymes are only modestly affected by classic beta-lactam-based inhibitors, such as clavulanic acid. Conversely, small arylboronic acids inhibit these enzymes at sub-micromolar concentrations. Structural studies suggest these inhibitors bind to a well-defined cleft in the group I beta-lactamase AmpC; this cleft binds the ubiquitous R1 side chain of beta-lactams. Intriguingly, much of this cleft is left unoccupied by the small arylboronic acids.
Organizational Affiliation: 
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA.