Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties

Abstract Quorum quenching lactonases are enzymes that are capable of disrupting bacterial signaling based on acyl homoserine lactones (AHL) via their enzymatic degradation. In particular, lactonases have therefore been demonstrated to inhibit bacterial behaviors that depend on these chemicals, such...

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Autores principales:	Celine Bergonzi, Michael Schwab, Tanushree Naik, David Daudé, Eric Chabrière, Mikael Elias
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bb65ef27405b41f9b1f33f9fd73010ea
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spelling	oai:doaj.org-article:bb65ef27405b41f9b1f33f9fd73010ea2021-12-02T15:08:03ZStructural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties10.1038/s41598-018-28988-52045-2322https://doaj.org/article/bb65ef27405b41f9b1f33f9fd73010ea2018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28988-5https://doaj.org/toc/2045-2322Abstract Quorum quenching lactonases are enzymes that are capable of disrupting bacterial signaling based on acyl homoserine lactones (AHL) via their enzymatic degradation. In particular, lactonases have therefore been demonstrated to inhibit bacterial behaviors that depend on these chemicals, such as the formation of biofilms or the expression of virulence factors. Here we characterized biochemically and structurally a novel representative from the metallo-β-lactamase superfamily, named AaL that was isolated from the thermoacidophilic bacterium Alicyclobacillus acidoterrestris. AaL is a potent quorum quenching enzyme as demonstrated by its ability to inhibit the biofilm formation of Acinetobacter baumannii. Kinetic studies demonstrate that AaL is both a proficient and a broad spectrum enzyme, being capable of hydrolyzing a wide range of lactones with high rates (kcat/KM > 105 M−1.s−1). Additionally, AaL exhibits unusually low KM values, ranging from 10 to 80 µM. Analysis of AaL structures bound to phosphate, glycerol, and C6-AHL reveals a unique hydrophobic patch (W26, F87 and I237), involved in substrate binding, possibly accounting for the enzyme’s high specificity. Identifying the specificity determinants will aid the development of highly specific quorum quenching enzymes as potential therapeutics.Celine BergonziMichael SchwabTanushree NaikDavid DaudéEric ChabrièreMikael EliasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Celine Bergonzi Michael Schwab Tanushree Naik David Daudé Eric Chabrière Mikael Elias Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
description	Abstract Quorum quenching lactonases are enzymes that are capable of disrupting bacterial signaling based on acyl homoserine lactones (AHL) via their enzymatic degradation. In particular, lactonases have therefore been demonstrated to inhibit bacterial behaviors that depend on these chemicals, such as the formation of biofilms or the expression of virulence factors. Here we characterized biochemically and structurally a novel representative from the metallo-β-lactamase superfamily, named AaL that was isolated from the thermoacidophilic bacterium Alicyclobacillus acidoterrestris. AaL is a potent quorum quenching enzyme as demonstrated by its ability to inhibit the biofilm formation of Acinetobacter baumannii. Kinetic studies demonstrate that AaL is both a proficient and a broad spectrum enzyme, being capable of hydrolyzing a wide range of lactones with high rates (kcat/KM > 105 M−1.s−1). Additionally, AaL exhibits unusually low KM values, ranging from 10 to 80 µM. Analysis of AaL structures bound to phosphate, glycerol, and C6-AHL reveals a unique hydrophobic patch (W26, F87 and I237), involved in substrate binding, possibly accounting for the enzyme’s high specificity. Identifying the specificity determinants will aid the development of highly specific quorum quenching enzymes as potential therapeutics.
format	article
author	Celine Bergonzi Michael Schwab Tanushree Naik David Daudé Eric Chabrière Mikael Elias
author_facet	Celine Bergonzi Michael Schwab Tanushree Naik David Daudé Eric Chabrière Mikael Elias
author_sort	Celine Bergonzi
title	Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
title_short	Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
title_full	Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
title_fullStr	Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
title_full_unstemmed	Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties
title_sort	structural and biochemical characterization of aal, a quorum quenching lactonase with unusual kinetic properties
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/bb65ef27405b41f9b1f33f9fd73010ea
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Structural and Biochemical Characterization of AaL, a Quorum Quenching Lactonase with Unusual Kinetic Properties

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