Structural Basis for Natural Lactonase and Promiscuous Phosphotriesterase Activities

Elias, Mikael; Dupuy, Jérôme; Merone, Luigia; Mandrich, Luigi; Porzio, Elena; Moniot, S.; Rochu, Daniel; Lecomte, Claude; Rossi, Mosè; Masson, Patrick; Manco, Giuseppe; Chabrière, Éric

doi:10.1016/j.jmb.2008.04.022

Cited by 157 publications

(171 citation statements)

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“…17) In addition, the thermostability allows rapid and efficient purification of the enzymes by simply heating which can remove the contaminating mesophiles, finally increasing the purification yield. 18) Their thermostability may endow quorum-quenching enzymes will high potential for development in biomedical applications.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization ofN-Acylhomoserine Lactonase from the Thermophilic Bacterium,Geobacillus caldoxylosilyticusYS-8

Seo

Lee

Pyun

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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Section: Discussionmentioning

confidence: 99%

Isolation and Characterization ofN-Acylhomoserine Lactonase from the Thermophilic Bacterium,Geobacillus caldoxylosilyticusYS-8

Seo

Lee

Pyun

et al. 2011

Bioscience, Biotechnology, and Biochemistry

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“…PTEs and PLLs, which belong to the amidohydrolase superfamily (Seibert & Raushel, 2005), share the same (/) 8 topology in which a bimetallic centre is coordinated by four histidines, an aspartic acid and a carboxylated lysine (Elias et al, 2008;Del Vecchio et al, 2009). The bimetallic centre activates a water molecule into a hydroxide ion, which serves as a nucleophile for the hydrolysis of OPs or AHLs.…”

Section: Introductionmentioning

confidence: 99%

“…The bimetallic centre activates a water molecule into a hydroxide ion, which serves as a nucleophile for the hydrolysis of OPs or AHLs. The catalytic centre is surrounded by two loops involved in the substrate specificity: loops 7 and 8 (Elias et al, 2008;Jackson et al, 2009). PTEs and PLLs differ mainly in the relative size and conformations of these loops, which account for the different substrate specificity of these enzymes (Afriat-Jurnou et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Crystallization and preliminary X-ray diffraction analysis of the lactonaseVmoLac fromVulcanisaeta moutnovskia

et al. 2013

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Phosphotriesterase-like lactonases (PLLs) are native lactonases that are capable of hydrolyzing lactones such as aliphatic lactones or acyl-homoserine lactones, which are involved in bacterial quorum sensing. Previously characterized PLLs are moreover endowed with a promiscuous phosphotriesterase activity and are therefore able to detoxify organophosphate insecticides. A novel PLL representative, dubbed VmoLac, has been identified from the hyperthermophilic crenarchaeon Vulcanisaeta moutnovskia. Because of its intrinsic high thermal stability, VmoLac may constitute an appealing candidate for engineering studies with the aim of producing an efficient biodecontaminant for organophosphorus compounds and a bacterial antivirulence agent. In combination with biochemical studies, structural information will allow the identification of the residues involved in substrate specificity and an understanding of the enzymatic catalytic mechanisms. Here, the expression, purification, crystallization and X-ray data collection at 2.4 Å resolution of VmoLac are reported.

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“…All AHS members have a (␤/␣) 8 -barrel structural fold and catalyze metaldependent hydrolysis reactions (3). The scissile bond cleaved varies between AHS enzymes, with C-O, P-O, P-S, C-N, C-S, and C-Cl bonds all having been reported to be hydrolyzed (4)(5)(6)(7)(8). In accordance with the metal-dependent mechanism, a mononuclear or binuclear metal binding site is observed in all AHS enzymes (9,10).…”

mentioning

confidence: 99%

Evolutionary Expansion of the Amidohydrolase Superfamily in Bacteria in Response to the Synthetic Compounds Molinate and Diuron

Sugrue

Fraser

Hopkins

et al. 2015

Appl Environ Microbiol

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The amidohydrolase superfamily has remarkable functional diversity, with considerable structural and functional annotation of known sequences. In microbes, the recent evolution of several members of this family to catalyze the breakdown of environmental xenobiotics is not well understood. An evolutionary transition from binuclear to mononuclear metal ion coordination at the active sites of these enzymes could produce large functional changes such as those observed in nature, but there are few clear examples available to support this hypothesis. To investigate the role of binuclear-mononuclear active-site transitions in the evolution of new function in this superfamily, we have characterized two recently evolved enzymes that catalyze the hydrolysis of the synthetic herbicides molinate (MolA) and phenylurea (PuhB). In this work, the crystal structures, mutagenesis, metal ion analysis, and enzyme kinetics of both MolA and PuhB establish that these enzymes utilize a mononuclear active site. However, bioinformatics and structural comparisons reveal that the closest putative ancestor of these enzymes had a binuclear active site, indicating that a binuclear-mononuclear transition has occurred. These proteins may represent examples of evolution modifying the characteristics of existing catalysts to satisfy new requirements, specifically, metal ion rearrangement leading to large leaps in activity that would not otherwise be possible.T he amidohydrolase superfamily (AHS) has been extensively studied, with Ͼ36,000 attributed sequences since its first classification in 1998, most of which are from bacteria (1, 2). All AHS members have a (␤/␣) 8 -barrel structural fold and catalyze metaldependent hydrolysis reactions (3). The scissile bond cleaved varies between AHS enzymes, with C-O, P-O, P-S, C-N, C-S, and C-Cl bonds all having been reported to be hydrolyzed (4-8). In accordance with the metal-dependent mechanism, a mononuclear or binuclear metal binding site is observed in all AHS enzymes (9, 10). The role of the metal ion(s) in catalysis varies, depending on the substrate being hydrolyzed and the enzyme involved (10, 11). Generally, one or two metals are enlisted to lower the pK a of a catalytic water molecule, favoring the formation of a nucleophilic hydroxide (12). A second metal may polarize the substrate directly, often at a carbonyl or phosphoryl bond, or stabilize a negative charge in the transition state (13,14).Enzymes within the AHS can be separated into subtypes on the basis of the specific metal binding ligands at the conserved mononuclear or binuclear metal binding sites. Since the comprehensive review published by Seibert and Raushel in 2005 (9), in which seven subtypes were defined, two additional subtypes have been identified (Table 1) (6,15). A typical binuclear metal binding site (subtypes I, II, and VI) is characterized by a bridging ligand (generally a glutamate or carboxylated lysine residue) that coordinates both (M ␣ and M ␤ ) metal ions (16-18). Mononuclear metal binding ligands are more variable, ...

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Structural Basis for Natural Lactonase and Promiscuous Phosphotriesterase Activities

Cited by 157 publications

References 34 publications

Isolation and Characterization ofN-Acylhomoserine Lactonase from the Thermophilic Bacterium,Geobacillus caldoxylosilyticusYS-8

Isolation and Characterization ofN-Acylhomoserine Lactonase from the Thermophilic Bacterium,Geobacillus caldoxylosilyticusYS-8

Crystallization and preliminary X-ray diffraction analysis of the lactonaseVmoLac fromVulcanisaeta moutnovskia

Evolutionary Expansion of the Amidohydrolase Superfamily in Bacteria in Response to the Synthetic Compounds Molinate and Diuron

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