Structural highlights
Publication Abstract from PubMedQuorum quenching lactonases are enzymes capable of hydrolyzing lactones, including N-acyl homoserine lactones (AHLs). AHLs are molecules known as signals in bacterial communication dubbed quorum sensing. Bacterial signal disruption by lactonases was previously reported to inhibit behaviors regulated by quorum sensing such as the expression of virulence factors and the formation of biofilms. Here, we report the enzymatic and structural characterization of a novel lactonase representative from the metallo-beta-lactamase superfamily, dubbed GcL. GcL is both a broad spectrum and a highly proficient lactonase, with kcat/KM values in the range of 104 to 106 M-1.s-1. Analysis of GcL structures obtained free, and in complex with AHL substrates of different acyl chain length, namely C4-AHL and 3-oxo-C12-AHL allowed us to elucidate their respective binding modes. Structures reveal three sub-sites in the binding crevice: (i) the small sub-site where chemistry is performed on the lactone ring; (ii) a hydrophobic ring that accommodates the amide group of AHLs and small acyl chains; and (iii) the outer, hydrophilic sub-site that extends to the protein surface. Unexpectedly, the absence of structural accommodation for long substrate acyl chains seem to relate to the enzyme's broad substrate specificity. The Structural Determinants Accounting for the Broad Substrate Specificity of the Quorum Quenching Lactonase GcL.,Bergonzi C, Schwab M, Naik T, Elias M Chembiochem. 2019 Mar 12. doi: 10.1002/cbic.201900024. PMID:30864300[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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