4DLN
Crystal structure of the CFTR inhibitory factor Cif with the D129S mutation
Summary for 4DLN
| Entry DOI | 10.2210/pdb4dln/pdb |
| 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 | 136546.76 |
| Authors | Bahl, C.D.,Amacher, J.F.,Madden, D.R. (deposition date: 2012-02-06, release date: 2013-08-07, Last modification date: 2024-11-20) |
| 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 Cited by 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: 26136396DOI: 10.1002/anie.201503983 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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