RCSB PDB - 5WIP: TraE protein in complex with 2-(2-furyl)isonicotinic acid

 5WIP

TraE protein in complex with 2-(2-furyl)isonicotinic acid


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.62 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.221 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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This is version 1.2 of the entry. See complete history


Literature

Fragment-based screening identifies novel targets for inhibitors of conjugative transfer of antimicrobial resistance by plasmid pKM101.

Casu, B.Arya, T.Bessette, B.Baron, C.

(2017) Sci Rep 7: 14907-14907

  • DOI: https://doi.org/10.1038/s41598-017-14953-1
  • Primary Citation of Related Structures:  
    5WIC, 5WII, 5WIO, 5WIP

  • PubMed Abstract: 

    The increasing frequency of antimicrobial resistance is a problem of global importance. Novel strategies are urgently needed to understand and inhibit antimicrobial resistance gene transmission that is mechanistically related to bacterial virulence functions. The conjugative transfer of plasmids by type IV secretion systems is a major contributor to antimicrobial resistance gene transfer. Here, we present a structure-based strategy to identify inhibitors of type IV secretion system-mediated bacterial conjugation. Using differential scanning fluorimetry we screened a fragment library and identified molecules that bind the essential TraE protein of the plasmid pKM101 conjugation machinery. Co-crystallization revealed that fragments bind two alternative sites of the protein and one of them is a novel inhibitor binding site. Based on the structural information on fragment binding we designed novel small molecules that have improved binding affinity. These molecules inhibit the dimerization of TraE, bind to both inhibitor binding sites on TraE and inhibit the conjugative transfer of plasmid pKM101. The strategy presented here is generally applicable for the structure-based design of inhibitors of antimicrobial resistance gene transfer and of bacterial virulence.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, 2900 Boulevard Édouard-Montpetit, Montreal, QC, H3T 1J4, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Conjugal transfer protein
A, B, C, D
163Escherichia coliMutation(s): 0 
Gene Names: 
UniProt
Find proteins for Q17U16 (Escherichia coli)
Explore Q17U16 
Go to UniProtKB:  Q17U16
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ17U16
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
XXO
Query on XXO

Download Ideal Coordinates CCD File 
E [auth A]2-(furan-2-yl)pyridine-4-carboxylic acid
C10 H7 N O3
RDJBDQGUVODXPZ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.62 Å
  • R-Value Free: 0.274 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.221 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.39α = 90
b = 124.089β = 90
c = 109.914γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXphasing

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted XXOClick on this verticalbar to view details

Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Canadian Institutes of Health Research (CIHR)CanadaCIHR MOP-84239

Revision History  (Full details and data files)

  • Version 1.0: 2017-11-15
    Type: Initial release
  • Version 1.1: 2020-01-08
    Changes: Author supporting evidence
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description