Structural Basis for Natural Lactonase and Promiscuous Phosphotriesterase Activities

Mikael Elias, Jérôme Dupuy, Luigia Merone, Luigi Mandrich, Elena Porzio, Sébastien Moniot, Daniel Rochu, Claude Lecomte, Mosè Rossi, Patrick Masson, Giuseppe Manco, Eric Chabriere

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118 Scopus citations

Abstract

Organophosphates are the largest class of known insecticides, several of which are potent nerve agents. Consequently, organophosphate-degrading enzymes are of great scientific interest as bioscavengers and biodecontaminants. Recently, a hyperthermophilic phosphotriesterase (known as SsoPox), from the Archaeon Sulfolobus solfataricus, has been isolated and found to possess a very high lactonase activity. Here, we report the three-dimensional structures of SsoPox in the apo form (2.6 Å resolution) and in complex with a quorum-sensing lactone mimic at 2.0 Å resolution. The structure also reveals an unexpected active site topology, and a unique hydrophobic channel that perfectly accommodates the lactone substrate. Structural and mutagenesis evidence allows us to propose a mechanism for lactone hydrolysis and to refine the catalytic mechanism established for phosphotriesterases. In addition, SsoPox structures permit the correlation of experimental lactonase and phosphotriesterase activities and this strongly suggests lactonase activity as the cognate function of SsoPox. This example demonstrates that promiscuous activities probably constitute a large and efficient reservoir for the creation of novel catalytic activities.

Original languageEnglish (US)
Pages (from-to)1017-1028
Number of pages12
JournalJournal of Molecular Biology
Volume379
Issue number5
DOIs
StatePublished - Jun 20 2008
Externally publishedYes

Keywords

  • 3D structure
  • active-site mutants
  • hyperthermophilic enzymes
  • lactonase
  • phosphotriesterase

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    Elias, M., Dupuy, J., Merone, L., Mandrich, L., Porzio, E., Moniot, S., Rochu, D., Lecomte, C., Rossi, M., Masson, P., Manco, G., & Chabriere, E. (2008). Structural Basis for Natural Lactonase and Promiscuous Phosphotriesterase Activities. Journal of Molecular Biology, 379(5), 1017-1028. https://doi.org/10.1016/j.jmb.2008.04.022