The Molecular Structure and Catalytic Mechanism of a Quorum-Quenching N-Acyl-L-Homoserine Lactone Hydrolase

In many Gram-negative bacteria, including a number of pathogens such as Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusible N-acyl-L-homoserine lactones (AHLs) as intercellular messenger molecul...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-12, Vol.102 (49), p.17606-17611
Main Authors: Myung Hee Kim, Won-Chan Choi, Hye Ok Kang, Jong Suk Lee, Beom Sik Kang, Kyung-Jin Kim, Zygmunt S. Derewenda, Tae-Kwang Oh, Choong Hwan Lee, Lee, Jung-Kee
Format: Article
Language:English
Subjects:
Atoms
Bacillus thuringiensis
Bacillus thuringiensis - enzymology
Bacillus thuringiensis - genetics
Bacteria
Binding Sites
Biochemistry
Biological Sciences
Carboxylic Ester Hydrolases - chemistry
Carboxylic Ester Hydrolases - genetics
Carboxylic Ester Hydrolases - metabolism
Catalysis
Cations, Divalent - chemistry
Crystal structure
Enzyme substrates
Enzymes
Erwinia carotovora
Hydrogen bonds
Ions
Lactones
Models, Molecular
Molecules
Mutation - genetics
Oxygen
Protein Structure, Tertiary
Pseudomonas aeruginosa
Substrate Specificity
Zinc
Zinc - chemistry
Zinc - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:In many Gram-negative bacteria, including a number of pathogens such as Pseudomonas aeruginosa and Erwinia carotovora, virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusible N-acyl-L-homoserine lactones (AHLs) as intercellular messenger molecules. A number of organisms also contain genes coding for lactonases that hydrolyze AHLs into inactive products, thereby blocking the quorum-sensing systems. Consequently, these enzymes attract intense interest for the development of antiinfection therapies. However, the catalytic mechanism of AHL-lactonase is poorly understood and subject to controversy. We here report a 2.0-Å resolution structure of the AHL-lactonase from Bacillus thuringiensis and a 1.7-Å crystal structure of its complex with L-homoserine lactone. Despite limited sequence similarity, the enzyme shows remarkable structural similarities to glyoxalase II and RNase Z proteins, members of the metallo-β-lactamase superfamily. We present experimental evidence that AHL-lactonase is a metalloenzyme containing two zinc ions involved in catalysis, and we propose a catalytic mechanism for bacterial metallo-AHL-lactonases.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0504996102