2RCX

AmpC Beta-lactamase in complex with (1R)-1-(2-Thiophen-2-yl-acetylamino)-1-(3-(2-carboxyvinyl)-phenyl) methylboronic acid

Summary for 2RCX

• Entry DOI: 10.2210/pdb2rcx/pdb
• Related: 1FSW 1KE4 1MXO
• Descriptor: Beta-lactamase, (1R)-1-(2-THIOPHEN-2-YL-ACETYLAMINO)-1-(3-(2-CARBOXYVINYL)-PHENYL) METHYLBORONIC ACID, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: ampc, beta-lactamase, cephalosporinase, serine hydrolase, antibiotic resistance, periplasm, hydrolase
• Biological source: Escherichia coli
• Cellular location: Periplasm: P00811
• Total number of polymer chains: 2
• Total formula weight: 80056.14

Authors

Morandi, F.,Morandi, S.,Prati, F.,Shoichet, B.K. (deposition date: 2007-09-20, release date: 2007-11-27, Last modification date: 2024-10-30)

Primary citation

Morandi, S.,Morandi, F.,Caselli, E.,Shoichet, B.K.,Prati, F.
Structure-based optimization of cephalothin-analogue boronic acids as beta-lactamase inhibitors
Bioorg.Med.Chem., 16:1195-1205, 2008

PubMed Abstract: 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.

PubMed: 17997318
DOI: 10.1016/j.bmc.2007.10.075

Experimental method

X-RAY DIFFRACTION (2 Å)