Open AccessThe molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase
Author(s) -
Myung Hee Kim,
Won-Chan Choi,
Hye Ok Kang,
Jong Suk Lee,
Beom Sik Kang,
Kyungjin Kim,
Zygmunt S. Derewenda,
Tae-Kwang Oh,
Choong Hwan Lee,
Jung-Kee Lee
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0504996102
Subject(s) - quorum sensing , quorum quenching , homoserine , hydrolase , biochemistry , chemistry , biofilm , bacteria , enzyme , virulence , biology , microbiology and biotechnology , stereochemistry , gene , genetics
In many Gram-negative bacteria, including a number of pathogens such asPseudomonas aeruginosa andErwinia carotovora , virulence factor production and biofilm formation are linked to the quorum-sensing systems that use diffusibleN- 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 fromBacillus thuringiensis and a 1.7-Å crystal structure of its complex withl -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.