2rcx | pdb_00002rcx
|
AmpC Beta-lactamase in complex with (1R)-1-(2-Thiophen-2-yl-acetylamino)-1-(3-(2-carboxyvinyl)-phenyl) methylboronic acid
Overview
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.
About this Structure
2RCX is a Single protein structure of sequence from Escherichia coli with PO4 and SM4 as ligands. Active as Beta-lactamase, with EC number 3.5.2.6 Full crystallographic information is available from OCA.
Reference
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. 2007 Nov 6;. PMID:17997318
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