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The quorum-quenching N -acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket

Bokhove, Marcel, Jimenez, Pol Nadal, Quax, Wim J., Dijkstra, Bauke W.·2010·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0911839107
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Abstract

In many Gram-negative pathogens, their virulent behavior is regulated by quorum sensing, in which diffusible signals such as N -acyl homoserine lactones (AHLs) act as chemical messaging compounds. Enzymatic degradation of these diffusible signals by, e.g., lactonases or amidohydrolases abolishes AHL regulated virulence, a process known as quorum quenching. Here we report the first crystal structure of an AHL amidohydrolase, the AHL acylase PvdQ from Pseudomonas aeruginosa . PvdQ has a typical α/β heterodimeric Ntn-hydrolase fold, similar to penicillin G acylase and cephalosporin acylase. However, it has a distinct, unusually large, hydrophobic binding pocket, ideally suited to recognize C12 fatty acid-like chains of AHLs. Binding of a C12 fatty acid or a 3-oxo-C12 fatty acid induces subtle conformational changes to accommodate the aliphatic chain. Furthermore, the structure of a covalent ester intermediate identifies Serβ1 as the nucleophile and Asnβ269 and Valβ70 as the oxyanion hole residues in the AHL degradation process. Our structures show the versatility of the Ntn-hydrolase scaffold and can serve as a structural paradigm for Ntn-hydrolases with similar substrate preference. Finally, the quorum-quenching capabilities of PvdQ may be utilized to suppress the quorum-sensing machinery of pathogens.

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Metadata

Authors
Bokhove, M., Jimenez, P. N., Quax, W. J., & Dijkstra, B. W.
Affiliations
  • Laboratory of Biophysical Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands; and
  • Department of Pharmaceutical Biology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2009-12-22
Volume
107
Issue
2
Pages
686-691
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.0911839107
Cited by
148
References
0
Language
en

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CoChat. (2026). Citation check: The quorum-quenching N -acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket. https://app.cochat.ai/papers/10.1073/pnas.0911839107
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Bokhove, M., Jimenez, P. N., Quax, W. J., & Dijkstra, B. W. (2010). The quorum-quenching N -acyl homoserine lactone acylase PvdQ is an Ntn-hydrolase with an unusual substrate-binding pocket. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0911839107

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