5NDE

Crystal structure of metallo-beta-lactamase SPM-1 in space group P4222

5NDE の概要

• エントリーDOI: 10.2210/pdb5nde/pdb
• 分子名称: Beta-lactamase IMP-1, ZINC ION, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: lactamase, inhibitor, cyclobutanone, 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: 57162.44

構造登録者

Hinchliffe, P.,Spencer, J. (登録日: 2017-03-08, 公開日: 2018-01-17, 最終更新日: 2024-01-17)

主引用文献

Abboud, M.I.,Kosmopoulou, M.,Krismanich, A.P.,Johnson, J.W.,Hinchliffe, P.,Brem, J.,Claridge, T.D.W.,Spencer, J.,Schofield, C.J.,Dmitrienko, G.I.
Cyclobutanone Mimics of Intermediates in Metallo-beta-Lactamase Catalysis.
Chemistry, 24:5734-5737, 2018

PubMed Abstract: The most important resistance mechanism to β-lactam antibiotics involves hydrolysis by two β-lactamase categories: the nucleophilic serine and the metallo-β-lactamases (SBLs and MBLs, respectively). Cyclobutanones are hydrolytically stable β-lactam analogues with potential to inhibit both SBLs and MBLs. We describe solution and crystallographic studies on the interaction of a cyclobutanone penem analogue with the clinically important MBL SPM-1. NMR experiments using F-labeled SPM-1 imply the cyclobutanone binds to SPM-1 with micromolar affinity. A crystal structure of the SPM-1:cyclobutanone complex reveals binding of the hydrated cyclobutanone through interactions with one of the zinc ions, stabilisation of the hydrate by hydrogen bonding to zinc-bound water, and hydrophobic contacts with aromatic residues. NMR analyses using a C-labeled cyclobutanone support assignment of the bound species as the hydrated ketone. The results inform on how MBLs bind substrates and stabilize tetrahedral intermediates. They support further investigations on the use of transition-state and/or intermediate analogues as inhibitors of all β-lactamase classes.

PubMed: 29250863
DOI: 10.1002/chem.201705886

実験手法

X-RAY DIFFRACTION (1.7 Å)