title: The molecular structure and catalytic mechanism of a quorum-quenching N-acyl-L-homoserine lactone hydrolase.
abstract: 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-angstroms resolution structure of the AHL-lactonase from Bacillus thuringiensis and a 1.7-angstroms 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-beta-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.
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejon 305-600, Korea.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Won-Chan
authors.initials: WC
authors.lastname: Choi
authors.forename: Hye Ok
authors.initials: HO
authors.lastname: Kang
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Lee
authors.forename: Beom Sik
authors.initials: BS
authors.lastname: Kang
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Kim
authors.forename: Zygmunt S
authors.initials: ZS
authors.lastname: Derewenda
authors.forename: Tae-Kwang
authors.initials: TK
authors.lastname: Oh
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Lee
authors.forename: Jung-Kee
authors.initials: JK
authors.lastname: Lee
mesh_terms: D001413:Bacillus thuringiensis / Q000201:enzymology* / Q000235:genetics; D001665:Binding Sites; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D002413:Cations, Divalent / Q000737:chemistry; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D002265:Carboxylic Ester Hydrolases; C432003:N-acyl homoserine lactonase; D015032:Zinc