4DLN

Crystal structure of the CFTR inhibitory factor Cif with the D129S mutation

4DLN の概要

• エントリーDOI: 10.2210/pdb4dln/pdb
• 分子名称: Putative hydrolase (2 entities in total)
• 機能のキーワード: alpha beta hydrolase, epoxide hydrolase, secreted, hydrolase
• 由来する生物種: Pseudomonas aeruginosa
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 136546.76

構造登録者

Bahl, C.D.,Amacher, J.F.,Madden, D.R. (登録日: 2012-02-06, 公開日: 2013-08-07, 最終更新日: 2024-11-20)

主引用文献

Bahl, C.D.,Hvorecny, K.L.,Bomberger, J.M.,Stanton, B.A.,Hammock, B.D.,Morisseau, C.,Madden, D.R.
Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR.
Angew.Chem.Int.Ed.Engl., 54:9881-9885, 2015

PubMed Abstract: Opportunistic pathogens exploit diverse strategies to sabotage host defenses. Pseudomonas aeruginosa secretes the CFTR inhibitory factor Cif and thus triggers loss of CFTR, an ion channel required for airway mucociliary defense. However, the mechanism of action of Cif has remained unclear. It catalyzes epoxide hydrolysis, but there is no known role for natural epoxides in CFTR regulation. It was demonstrated that the hydrolase activity of Cif is strictly required for its effects on CFTR. A small-molecule inhibitor that protects this key component of the mucociliary defense system was also uncovered. These results provide a basis for targeting the distinctive virulence chemistry of Cif and suggest an unanticipated role of physiological epoxides in intracellular protein trafficking.

PubMed: 26136396
DOI: 10.1002/anie.201503983

実験手法

X-RAY DIFFRACTION (1.55 Å)