LAUSR

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.