4ATT

FimH lectin domain co-crystal with a alpha-D-mannoside O-linked to a propynyl para methoxy phenyl


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.25 Å
  • R-Value Free: 0.177 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.151 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 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.Bouchaert, 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
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FIMH158Escherichia coli UTI89Mutation(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 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
HNV
Query on HNV

Download Ideal Coordinates CCD File 
B [auth A]3-(4-methoxyphenyl)prop-2-yn-1-yl alpha-D-mannopyranoside
C16 H20 O7
UYJNIDIDTZJFNU-OWYFMNJBSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
HNV Binding MOAD:  4ATT Kd: 104.6 (nM) from 1 assay(s)
PDBBind:  4ATT Kd: 53 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.25 Å
  • R-Value Free: 0.177 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.151 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 31.01α = 90
b = 42.3β = 90
c = 96.35γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-05-22
    Type: Initial release
  • Version 1.1: 2013-12-25
    Changes: Database references
  • Version 1.2: 2014-06-18
    Changes: Database references
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Other
  • Version 1.4: 2023-12-20
    Changes: Data collection, Database references, Refinement description, Structure summary