6BFY

Crystal structure of enolase from Escherichia coli with bound 2-phosphoglycerate substrate

6BFY の概要

• エントリーDOI: 10.2210/pdb6bfy/pdb
• 関連するPDBエントリー: 6BFZ
• 分子名称: Enolase, 2-PHOSPHOGLYCERIC ACID, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: enolase, substrate, 2-phosphoglycerate, escherichia coli, lyase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 288039.70

構造登録者

Erlandsen, H.,Wright, D.,Krucinska, J. (登録日: 2017-10-27, 公開日: 2018-10-31, 最終更新日: 2023-10-04)

主引用文献

Krucinska, J.,Falcone, E.,Erlandsen, H.,Hazeen, A.,Lombardo, M.N.,Estrada, A.,Robinson, V.L.,Anderson, A.C.,Wright, D.L.
Structural and Functional Studies of Bacterial Enolase, a Potential Target against Gram-Negative Pathogens.
Biochemistry, 58:1188-1197, 2019

PubMed Abstract: Enolase is a glycolytic metalloenzyme involved in carbon metabolism. The advantage of targeting enolase lies in its essentiality in many biological processes such as cell wall formation and RNA turnover and as a plasminogen receptor. We initially used a DARTS assay to identify enolase as a target in Escherichia coli. The antibacterial activities of α-, β-, and γ-substituted seven-member ring tropolones were first evaluated against four strains representing a range of Gram-negative bacteria. We observed that the chemical properties and position of the substituents on the tropolone ring play an important role in the biological activity of the investigated compounds. Both α- and β-substituted phenyl derivatives of tropolone were the most active with minimum inhibitory concentrations in the range of 11-14 μg/mL. The potential inhibitory activity of the synthetic tropolones was further evaluated using an enolase inhibition assay, X-ray crystallography, and molecular docking simulations. The catalytic activity of enolase was effectively inhibited by both the naturally occurring β-thujaplicin and the α- and β-substituted phenyl derivatives of tropolones with IC values in range of 8-11 μM. Ligand binding parameters were assessed by isothermal titration calorimetry and differential scanning calorimetry techniques and agreed with the in vitro data. Our studies validate the antibacterial potential of tropolones with careful consideration of the position and character of chelating moieties for stronger interaction with metal ions and residues in the enolase active site.

PubMed: 30714720
DOI: 10.1021/acs.biochem.8b01298

実験手法

X-RAY DIFFRACTION (1.81 Å)