3kd2

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Crystal structure of the CFTR inhibitory factor CifCrystal structure of the CFTR inhibitory factor Cif

Structural highlights

3kd2 is a 4 chain structure with sequence from Pseudomonas aeruginosa UCBPP-PA14. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0H2ZD27_PSEAB

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Cystic fibrosis transmembrane conductance regulator (CFTR) inhibitory factor (Cif) is a virulence factor secreted by Pseudomonas aeruginosa that reduces the quantity of CFTR in the apical membrane of human airway epithelial cells. Initial sequence analysis suggested that Cif is an epoxide hydrolase (EH), but its sequence violates two strictly conserved EH motifs and also is compatible with other alpha/beta hydrolase family members with diverse substrate specificities. To investigate the mechanistic basis of Cif activity, we have determined its structure at 1.8-A resolution by X-ray crystallography. The catalytic triad consists of residues Asp129, His297, and Glu153, which are conserved across the family of EHs. At other positions, sequence deviations from canonical EH active-site motifs are stereochemically conservative. Furthermore, detailed enzymatic analysis confirms that Cif catalyzes the hydrolysis of epoxide compounds, with specific activity against both epibromohydrin and cis-stilbene oxide, but with a relatively narrow range of substrate selectivity. Although closely related to two other classes of alpha/beta hydrolase in both sequence and structure, Cif does not exhibit activity as either a haloacetate dehalogenase or a haloalkane dehalogenase. A reassessment of the structural and functional consequences of the H269A mutation suggests that Cif's effect on host-cell CFTR expression requires the hydrolysis of an extended endogenous epoxide substrate.

Crystal structure of the cystic fibrosis transmembrane conductance regulator inhibitory factor Cif reveals novel active-site features of an epoxide hydrolase virulence factor.,Bahl CD, Morisseau C, Bomberger JM, Stanton BA, Hammock BD, O'Toole GA, Madden DR J Bacteriol. 2010 Apr;192(7):1785-95. Epub 2010 Jan 29. PMID:20118260[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Bahl CD, Morisseau C, Bomberger JM, Stanton BA, Hammock BD, O'Toole GA, Madden DR. Crystal structure of the cystic fibrosis transmembrane conductance regulator inhibitory factor Cif reveals novel active-site features of an epoxide hydrolase virulence factor. J Bacteriol. 2010 Apr;192(7):1785-95. Epub 2010 Jan 29. PMID:20118260 doi:10.1128/JB.01348-09

3kd2, resolution 1.80Å

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OCA