6OOE

CTX-M-27 Beta Lactamase with Compound 20

6OOE の概要

• エントリーDOI: 10.2210/pdb6ooe/pdb
• 分子名称: Beta-lactamase, 3-(1H-tetrazol-5-yl)-N-[3-(1H-tetrazol-5-yl)phenyl]-5-(trifluoromethyl)benzamide (3 entities in total)
• 機能のキーワード: beta-lactamase, esbl, non covalent complex, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57538.25

構造登録者

Kemp, M.,Chen, Y. (登録日: 2019-04-23, 公開日: 2020-07-01, 最終更新日: 2024-10-23)

主引用文献

DeFrees, K.,Kemp, M.T.,ElHilali-Pollard, X.,Zhang, X.,Mohamed, A.,Chen, Y.,Renslo, A.R.
An Empirical Study of Amide-Heteroarene pi-Stacking Interactions Using Reversible Inhibitors of a Bacterial Serine Hydrolase.
Org Chem Front, 6:1749-1756, 2019

PubMed Abstract: Compared to aryl-aryl π-stacking interactions, the analogous stacking of heteroarenes on amide π systems is less well understood and vastly underutilized in structure-based drug design. Recent theoretical studies have delineated the important geometric coordinates of the interaction, some of which have been confirmed with synthetic model systems based on Rebek imides. Unfortunately, a broadly useful and tractable protein-ligand model system of this interaction has remained elusive. Here we employed a known inhibitor scaffold to study π-stacking of diverse heteroarene substituents on the amide face of Gly238 in the cephalosporinases CTX-M-14 and CTX-M-27. Biochemical inhibition constants ( ) and biophysical binding constants ( ) were determined for nineteen new analogues against both enzymes, while multiple high-resolution co-crystal structures revealed remarkably consistent placement of the probe heteroarene on Gly238. The data presented support the predicted importance of opposing dipoles in amide-heteroarene interactions and should be useful for evaluating other theoretical predictions concerning these interactions.

PubMed: 32774871
DOI: 10.1039/c9qo00342h

実験手法

X-RAY DIFFRACTION (1.26 Å)