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Function
CFTR inhibitory factor (Cif) is a virulance factor which catalyzes epoxide hydrolysis. Pseudomonas aeruginosa secretes Cif which causes the loss the ion channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR) which is required for airway mucocilliary defense of the host cell[1].
Structural highlights
The 3D structure of the complex between Cif and the epoxy hydrolysis intermediate shows the coordination by His and Tyr esidues which facilitate the epoxyde opening by a nucleophilic attack of Asp creating a hydroxyalkyl-enzyme intermediate[2].
- ↑ Bahl CD, Hvorecny KL, Bomberger JM, Stanton BA, Hammock BD, Morisseau C, Madden DR. Inhibiting an epoxide hydrolase virulence factor from Pseudomonas aeruginosa protects CFTR. Angew Chem Int Ed Engl. 2015 Jul 1. doi: 10.1002/anie.201503983. PMID:26136396 doi:https://dx.doi.org/10.1002/anie.201503983
- ↑ Hvorecny KL, Bahl CD, Kitamura S, Lee KSS, Hammock BD, Morisseau C, Madden DR. Active-Site Flexibility and Substrate Specificity in a Bacterial Virulence Factor: Crystallographic Snapshots of an Epoxide Hydrolase. Structure. 2017 May 2;25(5):697-707.e4. doi: 10.1016/j.str.2017.03.002. Epub 2017, Apr 6. PMID:28392259 doi:https://dx.doi.org/10.1016/j.str.2017.03.002
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3D structures of CFTR inhibitory factor
Updated on 22-January-2025
3kd2 - PaCif - Pseudomonas aeruginosa
3kda, 4dm7, 4dln, 4dmf, 4dmh, 4dmk, 3pi6, 4dmc - PaCif (mutant)
5tnh, 5tng, 5tni, 5tnl, 5tnk, 5tnn, 5tnm, 5tnd, 5tnf, 5tne, 5tnp, 5tnr, 5tnq, 5tns, 5tnj, 5jyc, 4dno, 4dnf - PaCif (mutant) + intermediate
4ehb - PaCif (mutant) + epoxyhexane
4eus - PaCif + hexanediol
4yx9, 5hka, 5hkb, 5hk9 - PaCif + inhibitor
8ee2, 8eln, 8evd, 8f6u, 8f6v, 8gjr - PaCif + nanobody
References
