4BUQ

Crystal structure of wild type FimH lectin domain in complex with heptyl alpha-D-mannopyrannoside


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.205 

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This is version 1.3 of the entry. See complete history


Literature

Validation of Reactivity Descriptors to Assess the Aromatic Stacking within the Tyrosine Gate of Fimh

Roos, G.Wellens, A.Touaibia, M.Yamakawa, N.Geerlings, P.Roy, R.Wyns, L.Bouckaert, J.

(2013) ACS Med Chem Lett 4: 1085

  • DOI: https://doi.org/10.1021/ml400269v
  • Primary Citation of Related Structures:  
    4ATT, 4AUJ, 4BUQ

  • PubMed Abstract: 

    Antagonists of the FimH adhesin, a protein almost universally present at the extremity of type-1 fimbriae expressed by Escherichia coli, have been abundantly in the spotlight as alternative treatments of urinary tract infections. The antagonists function as bacterial antiadhesives through highly specific α-d-mannose binding in a charged and polar pocket at the tip of the FimH lectin domain and by the stacking of alkyl or aromatic moieties substituted on the mannose with two tyrosine residues (Tyr48 and Tyr137) at the entrance of the mannose-binding pocket. Using high-resolution crystal data, interaction energies are calculated for the different observed aromatic stacking modes between the tyrosines and the antagonist. The dispersion component of the interaction energy correlates with the observed electron density. The quantum chemical reactivity descriptors local hardness and polarizability were successfully validated as prediction tools for ligand affinity in the tyrosine gate of FimH and therefore have potential for rapid drug screening.


  • Organizational Affiliation

    General Chemistry, Vrije Universiteit Brussel, Structural Biology Brussels, VIB and Vrije Universiteit Brussel, and Brussels Center for Redox Biology, Pleinlaan 2, 1050 Brussels, Belgium ; General Chemistry, Vrije Universiteit Brussel, Structural Biology Brussels, VIB and Vrije Universiteit Brussel, and Brussels Center for Redox Biology, Pleinlaan 2, 1050 Brussels, Belgium ; General Chemistry, Vrije Universiteit Brussel, Structural Biology Brussels, VIB and Vrije Universiteit Brussel, and Brussels Center for Redox Biology, Pleinlaan 2, 1050 Brussels, Belgium.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FIMH
A, B
158Escherichia coli UTI89Mutation(s): 0 
UniProt
Find proteins for A2IC68 (Escherichia coli)
Explore A2IC68 
Go to UniProtKB:  A2IC68
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA2IC68
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
KGM Binding MOAD:  4BUQ Kd: 7.3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.202 
  • R-Value Observed: 0.205 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 60.305α = 90
b = 68.07β = 90
c = 95.607γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALESdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-02-19
    Type: Initial release
  • Version 1.1: 2014-06-18
    Changes: Database references
  • Version 1.2: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Derived calculations, Other, Structure summary
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Refinement description, Structure summary