Three-dimensional structure of the quorum-quenching N-acyl homoserine lactone hydrolase from Bacillus thuringiensis.
The three-dimensional structure of the N-acyl-l-homoserine lactone hydrolase (AHL lactonase) from Bacillus thuringiensis has been determined, by using single-wavelength anomalous dispersion (SAD) phasing, to 1.6-angstroms resolution. AHLs are produced by many Gram-negative bacteria as signaling molecules used in quorum-sensing pathways that indirectly sense cell density and regulate communal behavior. Because of their importance in pathogenicity, quorum-sensing pathways have been suggested as potential targets for the development of novel therapeutics. Quorum-sensing can be disrupted by enzymes evolved to degrade these lactones, such as AHL lactonases. These enzymes are members of the metallo-beta-lactamase superfamily and contain two zinc ions in their active sites. The zinc ions are coordinated to a number of ligands, including a single oxygen of a bridging carboxylate and a bridging water/hydroxide ion, thought to be the nucleophile that hydrolyzes the AHLs to ring-opened products, which can no longer act as quorum signals.
Liu
Dali
D
Division of Medicinal Chemistry, College of Pharmacy, University of Texas, Austin, TX 78712, USA.
Lepore
Bryan W
BW
Petsko
Gregory A
GA
Thomas
Pei W
PW
Stone
Everett M
EM
Fast
Walter
W
Ringe
Dagmar
D
D001413:Bacillus thuringiensis / Q000201:enzymology*; D001665:Binding Sites; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D018360:Crystallography, X-Ray; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D015032:Zinc / Q000737:chemistry
D002265:Carboxylic Ester Hydrolases; C432003:N-acyl homoserine lactonase; D015032:Zinc; D005990:Glycerol