2UV0

Structure of the P. aeruginosa LasR ligand-binding domain bound to its autoinducer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 

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This is version 1.2 of the entry. See complete history


Literature

Molecular Insights Into Quorum Sensing in the Human Pathogen Pseudomonas Aeruginosa from the Structure of the Virulence Regulator Lasr Bound to its Autoinducer.

Bottomley, M.J.Muraglia, E.Bazzo, R.Carfi, A.

(2007) J Biol Chem 282: 13592

  • DOI: https://doi.org/10.1074/jbc.M700556200
  • Primary Citation of Related Structures:  
    2UV0

  • PubMed Abstract: 

    Many Gram-negative bacteria communicate via molecules called autoinducers to coordinate the activities of their populations. Such communication is termed quorum sensing and can regulate pathogenic virulence factor production and antimicrobial resistance. The quorum sensing system of Pseudomonas aeruginosa is currently the most intensively researched, because this bacterium is an opportunistic human pathogen annually responsible for the death of thousands of cystic fibrosis sufferers and many other immunocompromised individuals. Quorum sensing inhibitors can attenuate the pathogenicity of P. aeruginosa. Here we present the crystal structure of the P. aeruginosa LasR ligand-binding domain bound to its autoinducer 3-oxo-C(12)-acylhomoserine lactone. The structure is a symmetrical dimer, with each monomer exhibiting an alpha-beta-alpha fold similar to the TraR and SdiA quorum sensing proteins of Agrobacterium tumefaciens and Escherichia coli. The structure was determined up to 1.8-A resolution and reveals the atomic interactions between LasR and its autoinducer. The monomer structures of LasR, TraR, and SdiA are comparable but display differences in their quaternary organization. Inspection of their binding sites shows some unexpected variations resulting in quite different conformations of their bound autoinducers. We modeled interactions between LasR and various quorum sensing inhibitors, yielding insight into their possible mechanisms of action. The structure also provides a platform for the optimization, or de novo design, of quorum sensing inhibitors.


  • Organizational Affiliation

    Istituto di Ricerche di Biologia Molecolare, Via Pontina Km 30.600, 00040 Pomezia, Rome, Italy. matthew_bottomley@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
TRANSCRIPTIONAL ACTIVATOR PROTEIN LASRA [auth E],
B [auth F],
C [auth G],
D [auth H]
175Pseudomonas aeruginosa PAO1Mutation(s): 0 
UniProt
Find proteins for P25084 (Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1))
Explore P25084 
Go to UniProtKB:  P25084
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP25084
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
MSE
Query on MSE
A [auth E],
B [auth F],
C [auth G],
D [auth H]
L-PEPTIDE LINKINGC5 H11 N O2 SeMET
Binding Affinity Annotations 
IDSourceBinding Affinity
OHN BindingDB:  2UV0 EC50: min: 1.5, max: 139 (nM) from 4 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.209 
  • R-Value Observed: 0.211 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.82α = 90
b = 85.33β = 95.82
c = 75.51γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
CNXphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-03-27
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Refinement description, Version format compliance
  • Version 1.2: 2019-07-24
    Changes: Data collection, Derived calculations