5jyc | pdb_00005jyc

Crystal structure of the E153Q mutant of the CFTR inhibitory factor Cif containing the adducted 14,15-EET hydrolysis intermediate

spinqualitylabelsall models 5jyc, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5jyc is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EET Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Recurrent Pseudomonas aeruginosa infections coupled with robust, damaging neutrophilic inflammation characterize the chronic lung disease cystic fibrosis (CF). The proresolving lipid mediator, 15-epi lipoxin A4 (15-epi LXA4), plays a critical role in limiting neutrophil activation and tissue inflammation, thus promoting the return to tissue homeostasis. Here, we show that a secreted P. aeruginosa epoxide hydrolase, cystic fibrosis transmembrane conductance regulator inhibitory factor (Cif), can disrupt 15-epi LXA4 transcellular biosynthesis and function. In the airway, 15-epi LXA4 production is stimulated by the epithelial-derived eicosanoid 14,15-epoxyeicosatrienoic acid (14,15-EET). Cif sabotages the production of 15-epi LXA4 by rapidly hydrolyzing 14,15-EET into its cognate diol, eliminating a proresolving signal that potently suppresses IL-8-driven neutrophil transepithelial migration in vitro. Retrospective analyses of samples from patients with CF supported the translational relevance of these preclinical findings. Elevated levels of Cif in bronchoalveolar lavage fluid were correlated with lower levels of 15-epi LXA4, increased IL-8 concentrations, and impaired lung function. Together, these findings provide structural, biochemical, and immunological evidence that the bacterial epoxide hydrolase Cif disrupts resolution pathways during bacterial lung infections. The data also suggest that Cif contributes to sustained pulmonary inflammation and associated loss of lung function in patients with CF. Pseudomonas aeruginosa sabotages the generation of host proresolving lipid mediators.,Flitter BA, Hvorecny KL, Ono E, Eddens T, Yang J, Kwak DH, Bahl CD, Hampton TH, Morisseau C, Hammock BD, Liu X, Lee JS, Kolls JK, Levy BD, Madden DR, Bomberger JM Proc Natl Acad Sci U S A. 2017 Jan 3;114(1):136-141. doi:, 10.1073/pnas.1610242114. Epub 2016 Dec 15. PMID:27980032 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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