1UWF

1.7 A resolution structure of the receptor binding domain of the FimH adhesin from uropathogenic E. coli


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Receptor Binding Studies Disclose a Novel Class of High-Affinity Inhibitors of the Escherichia Coli Fimh Adhesin.

Bouckaert, J.Berglund, J.Schembri, M.De Genst, E.Cools, L.Wuhrer, M.Hung, C.Pinkner, J.Slattegard, R.Zavialov, A.Choudhury, D.Langermann, S.Hultgren, S.J.Wyns, L.Klemm, P.Oscarson, S.Knight, S.D.De Greve, H.

(2005) Mol Microbiol 55: 441

  • DOI: https://doi.org/10.1111/j.1365-2958.2004.04415.x
  • Primary Citation of Related Structures:  
    1TR7, 1UWF

  • PubMed Abstract: 

    Mannose-binding type 1 pili are important virulence factors for the establishment of Escherichia coli urinary tract infections (UTIs). These infections are initiated by adhesion of uropathogenic E. coli to uroplakin receptors in the uroepithelium via the FimH adhesin located at the tips of type 1 pili. Blocking of bacterial adhesion is able to prevent infection. Here, we provide for the first time binding data of the molecular events underlying type 1 fimbrial adherence, by crystallographic analyses of the FimH receptor binding domains from a uropathogenic and a K-12 strain, and affinity measurements with mannose, common mono- and disaccharides, and a series of alkyl and aryl mannosides. Our results illustrate that the lectin domain of the FimH adhesin is a stable and functional entity and that an exogenous butyl alpha-D-mannoside, bound in the crystal structures, exhibits a significantly better affinity for FimH (Kd = 0.15 microM) than mannose (Kd = 2.3 microM). Exploration of the binding affinities of alpha- d-mannosides with longer alkyl tails revealed affinities up to 5 nM. Aryl mannosides and fructose can also bind with high affinities to the FimH lectin domain, with a 100-fold improvement and 15-fold reduction in affinity, respectively, compared with mannose. Taken together, these relative FimH affinities correlate exceptionally well with the relative concentrations of the same glycans needed for the inhibition of adherence of type 1 piliated E. coli. We foresee that our findings will spark new ideas and initiatives for the development of UTI vaccines and anti-adhesive drugs to prevent anticipated and recurrent UTIs.


  • Organizational Affiliation

    Laboratorium voor Ultrastructuur, Vrije Universiteit Brussel and Vlaams Interuniversitair Instituut voor Biotechnologie, Building E, Pleinlaan 2, 1050 Brussels, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FIMH PROTEIN158Escherichia coli J96Mutation(s): 0 
UniProt
Find proteins for P08191 (Escherichia coli (strain K12))
Explore P08191 
Go to UniProtKB:  P08191
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP08191
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DEG
Query on DEG

Download Ideal Coordinates CCD File 
B [auth A]butyl alpha-D-mannopyranoside
C10 H20 O6
BZANQLIRVMZFOS-ZJDVBMNYSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
C [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DEG PDBBind:  1UWF Kd: 150 (nM) from 1 assay(s)
Binding MOAD:  1UWF Kd: 150 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.179 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 39.906α = 90
b = 41.636β = 90
c = 97.07γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2005-02-16
    Type: Initial release
  • Version 1.1: 2015-04-15
    Changes: Database references, Derived calculations, Non-polymer description, Other, Refinement description, Source and taxonomy, Version format compliance
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Derived calculations, Other, Structure summary
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Refinement description, Structure summary