7E9A

Crystal structure of KPC-2 in complex with (S)-2-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acrylic acid (4a-(S))

7E9A の概要

• エントリーDOI: 10.2210/pdb7e9a/pdb
• 分子名称: Beta-lactamase, 2-[(3S)-1-oxidanyl-3H-2,1-benzoxaborol-3-yl]prop-2-enoic acid, ACETIC ACID, ... (6 entities in total)
• 機能のキーワード: beta-lactamase, serine-beta-lactamase kpc-2, kpc-2, carbapenemase, hydrolase
• 由来する生物種: Klebsiella pneumoniae
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 114928.20

構造登録者

Li, G.-B.,Yan, Y.-H. (登録日: 2021-03-03, 公開日: 2021-08-04, 最終更新日: 2024-10-23)

主引用文献

Xiao, Y.C.,Chen, X.P.,Deng, J.,Yan, Y.H.,Zhu, K.R.,Li, G.,Yu, J.L.,Brem, J.,Chen, F.,Schofield, C.J.,Li, G.B.
Design and enantioselective synthesis of 3-( alpha-acrylic acid) benzoxaboroles to combat carbapenemase resistance.
Chem.Commun.(Camb.), 57:7709-7712, 2021

PubMed Abstract: Chiral 3-substituted benzoxaboroles were designed as carbapenemase inhibitors and efficiently synthesised via asymmetric Morita-Baylis-Hillman reaction. Some of the benzoxaboroles were potent inhibitors of clinically relevant carbapenemases and restored the activity of meropenem in bacteria harbouring these enzymes. Crystallographic analyses validate the proposed mechanism of binding to carbapenemases, i.e. in a manner relating to their antibiotic substrates. The results illustrate how combining a structure-based design approach with asymmetric catalysis can efficiently lead to potent β-lactamase inhibitors and provide a starting point to develop drugs combatting carbapenemases.

PubMed: 34259249
DOI: 10.1039/d1cc03026d

実験手法

X-RAY DIFFRACTION (2.25 Å)