4YX9

Crystal structure of the CFTR inhibitory factor Cif bound to tiratricol


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Inhibiting an Epoxide Hydrolase Virulence Factor from Pseudomonas aeruginosa Protects CFTR.

Bahl, C.D.Hvorecny, K.L.Bomberger, J.M.Stanton, B.A.Hammock, B.D.Morisseau, C.Madden, D.R.

(2015) Angew Chem Int Ed Engl 54: 9881-9885

  • DOI: https://doi.org/10.1002/anie.201503983
  • Primary Citation of Related Structures:  
    4DLN, 4DM7, 4DMF, 4DMH, 4DMK, 4YX9

  • 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.


  • Organizational Affiliation

    Department of Biochemistry, Geisel School of Medicine at Dartmouth, 7200 Vail Building, Hanover, NH 03755 (USA) http://www.dartmouth.edu/∼madden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CFTR inhibitory factor
A, B, C, D
301Pseudomonas aeruginosa UCBPP-PA14Mutation(s): 0 
Gene Names: PA14_26090
UniProt
Find proteins for A0A0M3KL26 (Pseudomonas aeruginosa (strain UCBPP-PA14))
Explore A0A0M3KL26 
Go to UniProtKB:  A0A0M3KL26
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0M3KL26
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
4HY Binding MOAD:  4YX9 Ki: 4500 (nM) from 1 assay(s)
BindingDB:  4YX9 IC50: 4700 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.195 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.165 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 169.628α = 90
b = 84.016β = 100.48
c = 89.522γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01-AI091699
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesT32-AI007519
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)United StatesT32-DK007301
Cystic Fibrosis FoundationUnited StatesMADDEN08G0

Revision History  (Full details and data files)

  • Version 1.0: 2015-07-15
    Type: Initial release
  • Version 1.1: 2015-08-26
    Changes: Other
  • Version 1.2: 2017-09-13
    Changes: Author supporting evidence, Derived calculations
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.4: 2023-09-27
    Changes: Data collection, Database references, Refinement description