4DM7

Crystal structure of the CFTR inhibitory factor Cif with the E153D mutation

Summary for 4DM7

• Entry DOI: 10.2210/pdb4dm7/pdb
• Related: 3KD2 3KDA 3PI6 4DLN 4DMC 4DMF 4DMH 4DMK 4DMO 4DNF
• Descriptor: Putative hydrolase (2 entities in total)
• Functional Keywords: alpha beta hydrolase, epoxide hydrolase, secreted, hydrolase
• Biological source: Pseudomonas aeruginosa
• Total number of polymer chains: 4
• Total formula weight: 136602.70

Authors

Bahl, C.D.,Madden, D.R. (deposition date: 2012-02-07, release date: 2013-08-07, Last modification date: 2024-10-16)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.36 Å)