Structural highlights
Function
AMPC_ECOLI This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Boronic acids have proved to be promising selective inhibitors of beta-lactamases, acting as transition state analogues. Starting from a previously described nanomolar inhibitor of AmpC beta-lactamase, three new inhibitors were designed to gain interactions with highly conserved residues, such as Asn343, and to bind more tightly to the enzyme. Among these, one was obtained by stereoselective synthesis and succeeded in placing its anionic group into the carboxylate binding site of the enzyme, as revealed by X-ray crystallography of the complex inhibitor/AmpC. Nevertheless, it failed at improving affinity, when compared to the lead from which it was derived. The origins of this structural and energetic discrepancy are discussed.
Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors.,Morandi S, Morandi F, Caselli E, Shoichet BK, Prati F Bioorg Med Chem. 2008 Feb 1;16(3):1195-205. Epub 2007 Nov 7. PMID:17997318[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Morandi S, Morandi F, Caselli E, Shoichet BK, Prati F. Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors. Bioorg Med Chem. 2008 Feb 1;16(3):1195-205. Epub 2007 Nov 7. PMID:17997318 doi:10.1016/j.bmc.2007.10.075
