6TS9

Crystal structure of GES-5 carbapenemase

6TS9 の概要

• エントリーDOI: 10.2210/pdb6ts9/pdb
• 分子名称: Beta-lactamase, DIMETHYL SULFOXIDE, BROMIDE ION, ... (5 entities in total)
• 機能のキーワード: carbapenemase, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62982.88

構造登録者

Maso, L.,Tondi, D.,Klein, R.,Montanari, M.,Bellio, C.,Celenza, G.,Brenk, R.,Cendron, L. (登録日: 2019-12-20, 公開日: 2020-03-04, 最終更新日: 2024-10-23)

主引用文献

Klein, R.,Cendron, L.,Montanari, M.,Bellio, P.,Celenza, G.,Maso, L.,Tondi, D.,Brenk, R.
Targeting the Class A Carbapenemase GES-5 via Virtual Screening.
Biomolecules, 10:-, 2020

PubMed Abstract: The worldwide spread of β-lactamases able to hydrolyze last resort carbapenems contributes to the antibiotic resistance problem and menaces the successful antimicrobial treatment of clinically relevant pathogens. Class A carbapenemases include members of the KPC and GES families. While drugs against KPC-type carbapenemases have recently been approved, for GES-type enzymes, no inhibitors have yet been introduced in therapy. Thus, GES carbapenemases represent important drug targets. Here, we present an in silico screening against the most prevalent GES carbapenemase, GES-5, using a lead-like compound library of commercially available compounds. The most promising candidates were selected for in vitro validation in biochemical assays against recombinant GES-5 leading to four derivatives active as high micromolar competitive inhibitors. For the best inhibitors, the ability to inhibit KPC-2 was also evaluated. The discovered inhibitors constitute promising starting points for hit to lead optimization.

PubMed: 32075131
DOI: 10.3390/biom10020304

実験手法

X-RAY DIFFRACTION (1.55 Å)