Structures of the N-Terminal Domain of PqsA in Complex with Anthraniloyl- and 6-Fluoroanthraniloyl-AMP: Substrate Activation in Pseudomonas Quinolone Signal (PQS) Biosynthesis

Chembiochem. 2017 Oct 18;18(20):2045-2055. doi: 10.1002/cbic.201700374. Epub 2017 Sep 18.


Pseudomonas aeruginosa, a prevalent pathogen in nosocomial infections and a major burden in cystic fibrosis, uses three interconnected quorum-sensing systems to coordinate virulence processes. At variance with other Gram-negative bacteria, one of these systems relies on 2-alkyl-4(1H)-quinolones (Pseudomonas quinolone signal, PQS) and might hence be an attractive target for new anti-infective agents. Here we report crystal structures of the N-terminal domain of anthranilate-CoA ligase PqsA, the first enzyme of PQS biosynthesis, in complex with anthraniloyl-AMP and with 6-fluoroanthraniloyl-AMP (6FABA-AMP) at 1.4 and 1.7 Å resolution. We find that PqsA belongs to an unrecognized subfamily of anthranilate-CoA ligases that recognize the amino group of anthranilate through a water-mediated hydrogen bond. The complex with 6FABA-AMP explains why 6FABA, an inhibitor of PQS biosynthesis, is a good substrate of PqsA. Together, our data might pave a way to new pathoblockers in P. aeruginosa infections.

Keywords: Pseudomonas aeruginosa; Pseudomonas quinolone signal; ligases; quorum-sensing; structural biology.

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Ligases / chemistry*
  • Ligases / metabolism*
  • Models, Molecular
  • Pseudomonas aeruginosa / cytology*
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / metabolism*
  • Quinolones / metabolism*
  • Quorum Sensing*
  • ortho-Aminobenzoates / chemistry
  • ortho-Aminobenzoates / metabolism*


  • Quinolones
  • ortho-Aminobenzoates
  • anthranilic acid
  • Ligases