6KBY

Crystal structure of a class C beta lactamase in complex with AMP

6KBY の概要

• エントリーDOI: 10.2210/pdb6kby/pdb
• 分子名称: Beta-lactamase, ADENOSINE MONOPHOSPHATE (3 entities in total)
• 機能のキーワード: crystal structures, class c beta-lactamase, acyl-enzyme complex, amp, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 41060.54

構造登録者

Bae, D.W.,Jung, Y.E.,An, Y.J.,Na, J.H.,Cha, S.S. (登録日: 2019-06-26, 公開日: 2019-10-16, 最終更新日: 2024-11-06)

主引用文献

Bae, D.W.,Jung, Y.E.,An, Y.J.,Na, J.H.,Cha, S.S.
Structural Insights into Catalytic Relevances of Substrate Poses in ACC-1.
Antimicrob.Agents Chemother., 63:-, 2019

PubMed Abstract: ACC-1 is a plasmid-encoded class C β-lactamase identified in clinical isolates of , , , and ACC-1-producing bacteria are susceptible to cefoxitin, whereas they are resistant to oxyimino cephalosporins. Here, we depict crystal structures of apo ACC-1, adenylylated ACC-1, and acylated ACC-1 complexed with cefotaxime and cefoxitin. ACC-1 has noteworthy structural alterations in the R2 loop, the Ω loop, and the Phe119 loop located along the active-site rim. The adenylate covalently bonded to the nucleophilic serine reveals a tetrahedral phosphorus mimicking the deacylation transition state. Cefotaxime in ACC-1 has a proper conformation for the substrate-assisted catalysis in that its C-4 carboxylate and N-5 nitrogen are adequately located to facilitate the deacylation reaction. In contrast, cefoxitin in ACC-1 has a distinct conformation, in which those functional groups cannot contribute to catalysis. Furthermore, the orientation of the deacylating water relative to the acyl carbonyl group in ACC-1 is unfavorable for nucleophilic attack.

PubMed: 31451494
DOI: 10.1128/AAC.01411-19

実験手法

X-RAY DIFFRACTION (1.097 Å)