title: Crystal structure of VmoLac, a tentative quorum quenching lactonase from the extremophilic crenarchaeon Vulcanisaeta moutnovskia.
abstract: A new representative of the Phosphotriesterase-Like Lactonases (PLLs) family from the hyperthermophilic crenarchaeon Vulcanisaeta moutnovskia has been characterized and crystallized. VmoLac is a native, proficient lactonase with promiscuous, low phosphotriesterase activity. VmoLac therefore represents an interesting candidate for engineering studies, with the aim of developing an efficient bacterial quorum-quenching agent. Here, we provide an extensive biochemical and kinetic characterization of VmoLac and describe the X-ray structures of the enzyme bound to a fatty acid and to its cognate substrate 3-oxo-C10 AHL (Acyl-Homoserine Lactone). The structures highlight possible structural determinants that may be involved in its extreme thermal stability (Tm = 128 °C). Moreover, the structure reveals that the substrate binding mode of VmoLac significantly differs from those of its close homologues, possibly explaining the substrate specificity of the enzyme. Finally, we describe the specific interactions between the enzyme and its substrate, and discuss the possible lactone hydrolysis mechanism of VmoLac.
authors: URMITE UMR CNRS-IRD 6236, IFR48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.
authors: Julien
authors: J
authors: Hiblot
authors: URMITE UMR CNRS-IRD 6236, IFR48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.
authors: Janek
authors: J
authors: Bzdrenga
authors: URMITE UMR CNRS-IRD 6236, IFR48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.
authors: Charlotte
authors: C
authors: Champion
authors: URMITE UMR CNRS-IRD 6236, IFR48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France.
authors: Eric
authors: E
authors: Chabriere
authors: University of Minnesota, Department of Biochemistry, Molecular Biology and Biophysics &Biotechnology Institute, St. Paul, MN 55108, USA.
authors: Mikael
authors: M
authors: Elias
mesh_terms: D054742:Acyl-Butyrolactones / Q000737:chemistry*; D001105:Archaea / Q000201:enzymology*; D019843:Archaeal Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D044345:Phosphoric Triester Hydrolases / Q000737:chemistry*
chemical_list: D054742:Acyl-Butyrolactones; D019843:Archaeal Proteins; D044345:Phosphoric Triester Hydrolases