title: High-resolution structures of AidH complexes provide insights into a novel catalytic mechanism for N-acyl homoserine lactonase.
abstract: Many pathogenic bacteria that infect humans, animals and plants rely on a quorum-sensing (QS) system to produce virulence factors. N-Acyl homoserine lactones (AHLs) are the best-characterized cell-cell communication signals in QS. The concentration of AHL plays a key role in regulating the virulence-gene expression and essential biological functions of pathogenic bacteria. N-Acyl homoserine lactonases (AHL-lactonases) have important functions in decreasing pathogenicity by degrading AHLs. Here, structures of the AHL-lactonase from Ochrobactrum sp. (AidH) in complex with N-hexanoyl homoserine lactone, N-hexanoyl homoserine and N-butanoyl homoserine are reported. The high-resolution structures together with biochemical analyses reveal convincing details of AHL degradation. No metal ion is bound in the active site, which is different from other AHL-lactonases, which have a dual Lewis acid catalysis mechanism. AidH contains a substrate-binding tunnel between the core domain and the cap domain. The conformation of the tunnel entrance varies with the AHL acyl-chain length, which contributes to the binding promiscuity of AHL molecules in the active site. It also supports the biochemical result that AidH is a broad catalytic spectrum AHL-lactonase. Taken together, the present results reveal the catalytic mechanism of the metal-independent AHL-lactonase, which is a typical acid-base covalent catalysis.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors.forename: Ang
authors.initials: A
authors.lastname: Gao
authors.forename: Gui Ying
authors.initials: GY
authors.lastname: Mei
authors.forename: Shun
authors.initials: S
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Qun
authors.initials: Q
authors.lastname: Tang
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Wen
authors.forename: Xiao Min
authors.initials: XM
authors.lastname: An
authors.forename: Li Qun
authors.initials: LQ
authors.lastname: Zhang
authors.forename: Xiao Xue
authors.initials: XX
authors.lastname: Yan
authors.forename: Dong Cai
authors.initials: DC
authors.lastname: Liang
mesh_terms: D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000235:genetics; D002384:Catalysis; D020134:Catalytic Domain / Q000235:genetics; D002450:Cell Communication / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D016297:Mutagenesis, Site-Directed; D042041:Ochrobactrum / Q000201:enzymology* / Q000472:pathogenicity; D053038:Quorum Sensing / Q000235:genetics; D013379:Substrate Specificity / Q000235:genetics
chemical_list: D002265:Carboxylic Ester Hydrolases; C432003:N-acyl homoserine lactonase