CFTR inhibitory factor

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].

3D structures of CFTR inhibitory factor3D 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

ReferencesReferences

↑ 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:http://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:http://dx.doi.org/10.1016/j.str.2017.03.002

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Jaime Prilusky

[1] 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:http://dx.doi.org/10.1002/anie.201503983

[2] 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:http://dx.doi.org/10.1016/j.str.2017.03.002

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