5OE6

Crystal structure of the N-terminal domain of PqsA in complex with 6-fluoroanthraniloyl-AMP (crystal form 1)

Summary for 5OE6

• Entry DOI: 10.2210/pdb5oe6/pdb
• Descriptor: Anthranilate--CoA ligase, 6-fluoroanthraniloyl-AMP, TRIETHYLENE GLYCOL, ... (4 entities in total)
• Functional Keywords: ligase, pqs, pqsa, anthranilate, anthraniloyl-amp, anthraniloyl-coa, pseudomonas quinolone signal, pseudomonas aeruginosa, quorum sensing, aryl-coa ligase, anl superfamily, fluor, 6faba, 6-fluoroanthranilate, 6-fluoroanthraniloyl-amp, 6faba-amp
• Biological source: Pseudomonas aeruginosa PAO1
• Total number of polymer chains: 4
• Total formula weight: 179668.28

Authors

Witzgall, F.,Ewert, W.,Blankenfeldt, W. (deposition date: 2017-07-07, release date: 2017-09-06, Last modification date: 2024-05-08)

Primary citation

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, 18:2045-2055, 2017

PubMed Abstract: 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.

PubMed: 28834007
DOI: 10.1002/cbic.201700374

Experimental method

X-RAY DIFFRACTION (1.67 Å)