Structural highlights
Function
[PQSA_PSEAE] Catalyzes the formation of anthraniloyl-CoA, which is the priming step for entry into the Pseudomonas quinolone signal (PQS) biosynthetic pathway. Also active on a variety of aromatic substrates, including benzoate and chloro and fluoro derivatives of anthranilate.[1] [2]
Publication Abstract from PubMed
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-negatives, one of these systems relies on alkylquinolones (Pseudomonas Quinolone Signal, PQS) and may hence be an attractive target for new anti-infectives. 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 6-fluoroanthraniloyl-AMP (6FABA-AMP) at 1.4 and 1.7 A resolution. We find that PqsA belongs to an unrecognized subfamily of anthranilate-CoA ligases that recognizes 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 may pave a way to new pathoblockers in P. aeruginosa infections.
Structures of the N-terminal domain of PqsA in complex with anthraniloyl- and 6-fluoroanthraniloyl-AMP: substrate activation in Pseudomonas Quinolone Signal (PQS) biosynthesis.,Witzgall F, Ewert W, Blankenfeldt W Chembiochem. 2017 Aug 18. doi: 10.1002/cbic.201700374. PMID:28834007[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Coleman JP, Hudson LL, McKnight SL, Farrow JM 3rd, Calfee MW, Lindsey CA, Pesci EC. Pseudomonas aeruginosa PqsA is an anthranilate-coenzyme A ligase. J Bacteriol. 2008 Feb;190(4):1247-55. Epub 2007 Dec 14. PMID:18083812 doi:http://dx.doi.org/10.1128/JB.01140-07
- ↑ Zhang YM, Frank MW, Zhu K, Mayasundari A, Rock CO. PqsD is responsible for the synthesis of 2,4-dihydroxyquinoline, an extracellular metabolite produced by Pseudomonas aeruginosa. J Biol Chem. 2008 Oct 24;283(43):28788-94. doi: 10.1074/jbc.M804555200. Epub 2008, Aug 26. PMID:18728009 doi:http://dx.doi.org/10.1074/jbc.M804555200
- ↑ Witzgall F, Ewert W, Blankenfeldt W. 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 Aug 18. doi: 10.1002/cbic.201700374. PMID:28834007 doi:http://dx.doi.org/10.1002/cbic.201700374
