The enzyme, characterized from the bacterium Pseudomonas aeruginosa, participates in the synthesis of the secondary metabolites 2-heptyl-3-hydroxy-4(1H)-quinolone and 4-hydroxy-2(1H)-quinolone. The enzyme transfers an anthraniloyl group from anthraniloyl-CoA to an internal L-cysteine residue, followed by its transfer to malonyl-CoA to produce a short-lived product that can cyclize spontaneously to form 4-hydroxy-2(1H)-quinolone. However, when EC 3.1.2.32, 2-aminobenzoylacetyl-CoA thioesterase, is present, it removes the CoA moiety from the product, forming the stable 2-aminobenzoylacetate.
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The expected taxonomic range for this enzyme is: Pseudomonas aeruginosa
The enzyme, characterized from the bacterium Pseudomonas aeruginosa, participates in the synthesis of the secondary metabolites 2-heptyl-3-hydroxy-4(1H)-quinolone and 4-hydroxy-2(1H)-quinolone. The enzyme transfers an anthraniloyl group from anthraniloyl-CoA to an internal L-cysteine residue, followed by its transfer to malonyl-CoA to produce a short-lived product that can cyclize spontaneously to form 4-hydroxy-2(1H)-quinolone. However, when EC 3.1.2.32, 2-aminobenzoylacetyl-CoA thioesterase, is present, it removes the CoA moiety from the product, forming the stable 2-aminobenzoylacetate.
initial catalytic step of PqsD is the transfer of the anthraniloyl moiety to residue Cys112 under hydrolysis of the anthraniloyl-CoA thioester. The second step in the reaction that leads to Cys112-anthraniloyl and CoA is a concerted reaction mechanism. The deprotonated sulfur atom of Cys112 performs a nucleophilic attack at the carbonyl carbon of anthraniloyl-CoA while the proton at Nepsilon of His257 is simultaneously shifted to the sulfur atom of CoA. During the reaction, His257 switches its protonation pattern. Only Nepsilon is protonated in the reactant state, whereas the uptake of a proton at Ndelta to deprotonation of Cys112 leads to a doubly protonated (positively charged) intermediate. From there, the proton at Nepsilon is subsequently transferred to the sulfur of CoA, leading to a net neutral product
at a concentration of 250 microM, both the 2-heptyl-4-hydroxyquinoline and Pseudomonas quinolone signal levels are strongly reduced by 77 and 42%, respectively, in Pseudomonas aeruginosa PA14 cultures. The 2,4-dihydroxyquinoline level increases in the presence of the compound. Addition of the compound to a 24 h old biofilm reduces the biovolume of the biofilm by 38% within a 24 h incubation period
4-hydroxy-2-alkylquinolines biosynthesis requires the PqsABCD enzymes and proceeds by a two-step pathway: First, PqsD mediates the synthesis of 2-aminobenzoylacetate from anthraniloyl-CoA and malonyl-CoA, then the decarboxylating coupling of 2-aminobenzoylacetate to an octanoate group linked to PqsC produces 4-hydroxy-2-heptylquinoline, the direct precursor of Pseudomonas quinolone signal. PqsB is tightly associated with PqsC and required for the second step
in addition to PqsABCD, PqsE has a role in 2-heptyl-4(1H)-quinolone synthesis. PqsE acts as thioesterase, hydrolyzing the biosynthetic intermediate 2-aminobenzoylacetyl-coenzyme A formed by PsqD to form 2-aminobenzoylacetate, the precursor of 2-heptyl-4(1H)-quinolone and 2-aminoacetophenone
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
crystal structures of the enzyme including the PqsD-anthranilate covalent intermediate and the inactive Cys112Ala active site mutant in complex with anthranilate. The crystallographic asymmetric unit contains a PqsD dimer. The PqsD monomer is composed of two nearly identical about 170 residue alphabetalaphabeta domains. Anthranilate-liganded residue Cys112 is positioned deep in the protein interior at the bottom of a 15 A long channel while a second anthraniloyl-CoA molecule is waiting in the cleft leading to the protein surface. Cys112, His257, and Asn287 form the FabH-like catalytic triad of PqsD
molecular dynamics simulations reveal a nucleophilic attack of the deprotonated sulfur of residue Cys112 at the carbonyl carbon of anthraniloyl-coenzyme A and a switch in the protonation pattern of His257 whereby Ndelta is protonated and the proton of Nepsilon? is shifted to the sulfur of CoA during the reaction
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2.3.1.262 anthraniloyl-CoA anthraniloyltransferase
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