1RO5

Crystal Structure of the AHL Synthase LasI


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.197 

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This is version 1.3 of the entry. See complete history


Literature

Structure of the Pseudomonas aeruginosa acyl-homoserinelactone synthase LasI.

Gould, T.A.Schweizer, H.P.Churchill, M.E.

(2004) Mol Microbiol 53: 1135-1146

  • DOI: https://doi.org/10.1111/j.1365-2958.2004.04211.x
  • Primary Citation of Related Structures:  
    1RO5

  • PubMed Abstract: 

    The LasI/LasR quorum-sensing system plays a pivotal role in virulence gene regulation of the opportunistic human pathogen, Pseudomonas aeruginosa. Here we report the crystal structure of the acyl-homoserine lactone (AHL) synthase LasI that produces 3-oxo-C12-AHL from the substrates 3-oxo-C12-acyl-carrier protein (acyl-ACP) and S-adenosyl-L-methionine. The LasI six-stranded beta sheet platform, buttressed by three alpha helices, forms a V-shaped substrate-binding cleft that leads to a tunnel passing through the enzyme that can accommodate the acyl-chain of acyl-ACP. This tunnel places no apparent restriction on acyl-chain length, in contrast to a restrictive hydrophobic pocket seen in the AHL-synthase EsaI. Interactions of essential conserved N-terminal residues, Arg23, Phe27 and Trp33, suggest that the N-terminus forms an enclosed substrate-binding pocket for S-adenosyl-L-methionine. Analysis of AHL-synthase surface residues identified a binding site for acyl-ACP, a role that was supported by in vivo reporter assay analysis of the mutated residues, including Arg154 and Lys150. This structure and the novel explanation of AHL-synthase acyl-chain-length selectivity promise to guide the design of Pseudomonas aeruginosa-specific quorum-sensing inhibitors as antibacterial agents.


  • Organizational Affiliation

    Department of Pharmacology, Program in Biomolecular Structure, The University of Colorado Health Sciences Center, 4200 E. Ninth Ave, Denver, CO 80262, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Autoinducer synthesis protein lasI201Pseudomonas aeruginosaMutation(s): 0 
Gene Names: LASIPA1432
UniProt
Find proteins for P33883 (Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1))
Explore P33883 
Go to UniProtKB:  P33883
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP33883
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.197 
  • Space Group: F 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 154.9α = 90
b = 154.9β = 90
c = 154.9γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
SOLVEphasing
RESOLVEphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-08-24
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2022-12-21
    Changes: Database references, Derived calculations