6LC7

Crystal structure of AmpC Ent385 free form

6LC7 の概要

• エントリーDOI: 10.2210/pdb6lc7/pdb
• 分子名称: Beta-lactamase, GLYCEROL, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: beta-lactamase, class c, ampc, hydrolase
• 由来する生物種: Enterobacter cloacae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 80669.87

構造登録者

Kawai, A.,Doi, Y. (登録日: 2019-11-18, 公開日: 2020-04-22, 最終更新日: 2023-11-22)

主引用文献

Kawai, A.,McElheny, C.L.,Iovleva, A.,Kline, E.G.,Sluis-Cremer, N.,Shields, R.K.,Doi, Y.
Structural Basis of Reduced Susceptibility to Ceftazidime-Avibactam and Cefiderocol inEnterobacter cloacaeDue to AmpC R2 Loop Deletion.
Antimicrob.Agents Chemother., 64:-, 2020

PubMed Abstract: Ceftazidime-avibactam and cefiderocol are two of the latest generation β-lactam agents that possess expanded activity against highly drug-resistant bacteria, including carbapenem-resistant Here, we show that structural changes in AmpC β-lactamases can confer reduced susceptibility to both agents. A multidrug-resistant clinical strain (Ent385) was found to be resistant to ceftazidime-avibactam and cefiderocol without prior exposure to either agent. The AmpC β-lactamase of Ent385 (AmpC) contained an alanine-proline deletion at positions 294 and 295 (A294_P295del) in the R2 loop. AmpC conferred reduced susceptibility to ceftazidime-avibactam and cefiderocol when cloned into TOP10. Purified AmpC showed increased hydrolysis of ceftazidime and cefiderocol compared to AmpC, in which the deletion was reverted. Comparisons of crystal structures of AmpC and AmpC, the canonical AmpC of complex, revealed that the two-residue deletion in AmpC induced drastic structural changes of the H-9 and H-10 helices and the R2 loop, which accounted for the increased hydrolysis of ceftazidime and cefiderocol. The potential for a single mutation in to confer reduced susceptibility to both ceftazidime-avibactam and cefiderocol requires close monitoring.

PubMed: 32284381
DOI: 10.1128/AAC.00198-20

実験手法

X-RAY DIFFRACTION (1.4 Å)