6ESZ

Crystal structure of PqsBC from Pseudomonas aeruginosa (crystal form 1)

Summary for 6ESZ

• Entry DOI: 10.2210/pdb6esz/pdb
• Descriptor: PqsC, PqsB, SULFATE ION, ... (6 entities in total)
• Functional Keywords: pseudomonas quinolone signal, transferase, fabh, hhq
• Biological source: Pseudomonas aeruginosa PAO1; More
• Total number of polymer chains: 4
• Total formula weight: 143588.88

Authors

Witzgall, F.,Blankenfeldt, W. (deposition date: 2017-10-25, release date: 2018-07-04, Last modification date: 2024-11-13)

Primary citation

Witzgall, F.,Depke, T.,Hoffmann, M.,Empting, M.,Bronstrup, M.,Muller, R.,Blankenfeldt, W.
The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH-like 2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) Biosynthesis Enzyme PqsBC.
Chembiochem, 19:1531-1544, 2018

PubMed Abstract: Pseudomonas aeruginosa is a bacterial pathogen that causes life-threatening infections in immunocompromised patients. It produces a large armory of saturated and mono-unsaturated 2-alkyl-4(1H)-quinolones (AQs) and AQ N-oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β-ketoacyl-acyl-carrier protein synthase III (FabH)-like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2-heptyl-4(1H)-quinolone (HHQ), by condensing octanoyl-coenzyme A (CoA) with 2-aminobenzoylacetate (2-ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium-chain acyl-CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono-unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl-binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH-enzymes, for which such structural transitions have been postulated but have never been observed.

PubMed: 29722462
DOI: 10.1002/cbic.201800153

Experimental method

X-RAY DIFFRACTION (1.84 Å)