6et1
Crystal structure of PqsBC from Pseudomonas aeruginosa (crystal form 2)
Structural highlights
FunctionPQSC_PSEAE Required for the biosynthesis of the quorum-sensing signaling molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal or PQS), which are important for biofilm formation and virulence. The PqsC/PqsB complex catalyzes the condensation of 2-aminobenzoylacetate (2-ABA) and octanoyl-CoA to form HHQ. First, PqsC acquires an octanoyl group from octanoyl-CoA and forms an octanoyl-PqsC intermediate. Then, together with PqsB, it catalyzes the coupling of 2-ABA with the octanoate group, leading to decarboxylation and dehydration, and resulting in closure of the quinoline ring.[1] [2] Publication Abstract from PubMedPseudomonas 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 beta-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 A 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. 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.,Witzgall F, Depke T, Hoffmann M, Empting M, Bronstrup M, Muller R, Blankenfeldt W Chembiochem. 2018 May 3. doi: 10.1002/cbic.201800153. PMID:29722462[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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