2RCX

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

2RCX の概要

• エントリーDOI: 10.2210/pdb2rcx/pdb
• 関連するPDBエントリー: 1FSW 1KE4 1MXO
• 分子名称: Beta-lactamase, (1R)-1-(2-THIOPHEN-2-YL-ACETYLAMINO)-1-(3-(2-CARBOXYVINYL)-PHENYL) METHYLBORONIC ACID, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: ampc, beta-lactamase, cephalosporinase, serine hydrolase, antibiotic resistance, periplasm, hydrolase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Periplasm: P00811
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80056.14

構造登録者

Morandi, F.,Morandi, S.,Prati, F.,Shoichet, B.K. (登録日: 2007-09-20, 公開日: 2007-11-27, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2 Å)