9IXO

Crystal structure of OXA-14

9IXO の概要

• エントリーDOI: 10.2210/pdb9ixo/pdb
• 関連するPDBエントリー: 9IXN
• 分子名称: Beta-lactamase (2 entities in total)
• 機能のキーワード: class d beta-lactamase, oxa-14, oxa-10 variant, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55789.35

構造登録者

Lee, C.E.,Park, Y.S.,Park, H.J.,Kang, L.W. (登録日: 2024-07-29, 公開日: 2024-10-23, 最終更新日: 2024-11-06)

主引用文献

Lee, C.E.,Park, Y.,Park, H.,Kwak, K.,Lee, H.,Yun, J.,Lee, D.,Lee, J.H.,Lee, S.H.,Kang, L.W.
Structural insights into alterations in the substrate spectrum of serine-beta-lactamase OXA-10 from Pseudomonas aeruginosa by single amino acid substitutions.
Emerg Microbes Infect, 13:2412631-2412631, 2024

PubMed Abstract: The extensive use of β-lactam antibiotics has led to significant resistance, primarily due to hydrolysis by β-lactamases. OXA class D β-lactamases can hydrolyze a wide range of β-lactam antibiotics, rendering many treatments ineffective. We investigated the effects of single amino acid substitutions in OXA-10 on its substrate spectrum. Broad-spectrum variants with point mutations were searched and biochemically verified. Three key residues, G157D, A124T, and N73S, were confirmed in the variants, and their crystal structures were determined. Based on an enzyme kinetics study, the hydrolytic activity against broad-spectrum cephalosporins, particularly ceftazidime, was significantly enhanced by the G157D mutation in loop 2. The A124T or N73S mutation close to loop 2 also resulted in higher ceftazidime activity. All structures of variants with point mutations in loop 2 or nearby exhibited increased loop 2 flexibility, which facilitated the binding of ceftazidime. These results highlight the effect of a single amino acid substitution in OXA-10 on broad-spectrum drug resistance. Structure-activity relationship studies will help us understand the drug resistance spectrum of β-lactamases, enhance the effectiveness of existing β-lactam antibiotics, and develop new drugs.

PubMed: 39361442
DOI: 10.1080/22221751.2024.2412631

実験手法

X-RAY DIFFRACTION (1.86 Å)