5FQB

Crystal Structure of Bacillus cereus Metallo-Beta-Lactamase with 2C

5FQB の概要

• エントリーDOI: 10.2210/pdb5fqb/pdb
• 関連するPDBエントリー: 5FQA
• 分子名称: BETA-LACTAMASE 2, ZINC ION, (4~{R})-4-[[4-(aminomethyl)phenyl]carbonylamino]-3,3-bis(oxidanyl)-2-oxa-3-boranuidabicyclo[4.4.0]deca-1(10),6,8-triene-10-carboxylic acid, ... (6 entities in total)
• 機能のキーワード: hydrolase, antibiotic resistance, lactamase
• 由来する生物種: BACILLUS CEREUS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25671.65

構造登録者

Cahill, S.T.,Brem, J.,McDonough, M.A.,Schofield, C.J. (登録日: 2015-12-08, 公開日: 2016-08-10, 最終更新日: 2024-01-10)

主引用文献

Brem, J.,Cain, R.,Cahill, S.,McDonough, M.A.,Clifton, I.J.,Jimenez-Castellanos, J.C.,Avison, M.B.,Spencer, J.,Fishwick, C.W.,Schofield, C.J.
Structural basis of metallo-beta-lactamase, serine-beta-lactamase and penicillin-binding protein inhibition by cyclic boronates.
Nat Commun, 7:12406-12406, 2016

PubMed Abstract: β-Lactamases enable resistance to almost all β-lactam antibiotics. Pioneering work revealed that acyclic boronic acids can act as 'transition state analogue' inhibitors of nucleophilic serine enzymes, including serine-β-lactamases. Here we report biochemical and biophysical analyses revealing that cyclic boronates potently inhibit both nucleophilic serine and zinc-dependent β-lactamases by a mechanism involving mimicking of the common tetrahedral intermediate. Cyclic boronates also potently inhibit the non-essential penicillin-binding protein PBP 5 by the same mechanism of action. The results open the way for development of dual action inhibitors effective against both serine- and metallo-β-lactamases, and which could also have antimicrobial activity through inhibition of PBPs.

PubMed: 27499424
DOI: 10.1038/ncomms12406

実験手法

X-RAY DIFFRACTION (1.899 Å)