Enzymes
UniProtKB help_outline | 1 proteins |
Enzyme class help_outline |
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- Name help_outline (2-aminobenzoyl)acetyl-CoA Identifier CHEBI:131447 Charge -4 Formula C30H39N8O18P3S InChIKeyhelp_outline OLOTULRNHWZRKJ-FUEUKBNZSA-J SMILEShelp_outline [C@@H]1(N2C3=C(C(=NC=N3)N)N=C2)O[C@H](COP(OP(OCC(C)([C@H](C(NCCC(NCCSC(CC(C4=CC=CC=C4N)=O)=O)=O)=O)O)C)(=O)[O-])(=O)[O-])[C@H]([C@H]1O)OP([O-])([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline (2-aminobenzoyl)acetate Identifier CHEBI:131446 Charge -1 Formula C9H8NO3 InChIKeyhelp_outline POAXUNDIOGWQOC-UHFFFAOYSA-M SMILEShelp_outline C=1(C(=CC=CC1)N)C(CC([O-])=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 3 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline CoA Identifier CHEBI:57287 (Beilstein: 11604429) help_outline Charge -4 Formula C21H32N7O16P3S InChIKeyhelp_outline RGJOEKWQDUBAIZ-IBOSZNHHSA-J SMILEShelp_outline CC(C)(COP([O-])(=O)OP([O-])(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1OP([O-])([O-])=O)n1cnc2c(N)ncnc12)[C@@H](O)C(=O)NCCC(=O)NCCS 2D coordinates Mol file for the small molecule Search links Involved in 1,500 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,431 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:49444 | RHEA:49445 | RHEA:49446 | RHEA:49447 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Structure elucidation and preliminary assessment of hydrolase activity of PqsE, the Pseudomonas quinolone signal (PQS) response protein.
Yu S., Jensen V., Seeliger J., Feldmann I., Weber S., Schleicher E., Haussler S., Blankenfeldt W.
In bacteria, the transcription of virulence genes is usually controlled by a cell density-dependent process known as "quorum sensing" (QS). QS relies on small diffusible signaling molecules that cross the bacterial cell wall and activate target transcription factors after a threshold concentration ... >> More
In bacteria, the transcription of virulence genes is usually controlled by a cell density-dependent process known as "quorum sensing" (QS). QS relies on small diffusible signaling molecules that cross the bacterial cell wall and activate target transcription factors after a threshold concentration has been reached. Besides two hierarchical QS circuits based on N-acylhomoserine lactones, the human opportunistic pathogen Pseudomonas aeruginosa integrates a signaling system that depends on 2-heptyl-3-hydroxy-4-quinolone, termed "Pseudomonas quinolone signal" (PQS). PQS is produced from genes encoded in the pqs operon, which in addition to the biosynthetic enzymes PqsA-D contains a fifth gene, pqsE, that is not required for production of PQS but whose disruption leads to loss of signal transduction in several but not all pqs operon-dependent processes. PqsE was hence termed "PQS response protein", but its exact mechanism of action is unknown. We have determined the crystal structure of recombinant PqsE and show that it possesses a metallo-beta-lactamase fold with an Fe(II)Fe(III) center in the active site. A copurified ligand was assigned as benzoate and may indicate that PqsE exerts its regulatory effect by converting a chorismate-derived molecule. Further, PqsE was found to slowly hydrolyze phosphodiesters including single- and double-stranded DNA as well as mRNA and also the thioester S-(4-nitrobenzoyl)mercaptoethane. Higher activity was observed after incubation with Co(2+) and, to lesser entent, Mn(2+), suggesting that the Fe(II)Fe(III) center of recombinant PqsE may be an artifact of heterologous expression. A crystal complex of the E182A mutant with bis-pNPP was obtained and suggests a catalytic mechanism for hydrolysis. << Less
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PqsE of Pseudomonas aeruginosa acts as pathway-specific thioesterase in the biosynthesis of alkylquinolone signaling molecules.
Drees S.L., Fetzner S.
Pseudomonas aeruginosa uses the alkylquinolones PQS (2-heptyl-3-hydroxy-4(1H)-quinolone) and HHQ (2-heptyl-4(1H)-quinolone) as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. The biosynthesis of HHQ is generally accepted ... >> More
Pseudomonas aeruginosa uses the alkylquinolones PQS (2-heptyl-3-hydroxy-4(1H)-quinolone) and HHQ (2-heptyl-4(1H)-quinolone) as quorum-sensing signal molecules, controlling the expression of many virulence genes as a function of cell population density. The biosynthesis of HHQ is generally accepted to require the pqsABCD gene products. We now reconstitute the biosynthetic pathway in vitro, and demonstrate that in addition to PqsABCD, PqsE has a role in HHQ synthesis. PqsE acts as thioesterase, hydrolyzing the biosynthetic intermediate 2-aminobenzoylacetyl-coenzyme A to form 2-aminobenzoylacetate, the precursor of HHQ and 2-aminoacetophenone. The role of PqsE can be taken over to some extent by the broad-specificity thioesterase TesB, explaining why the pqsE deletion mutant of P. aeruginosa still synthesizes HHQ. Interestingly, the pqsE mutant produces increased levels of 2,4-dihydroxyquinoline, resulting from intramolecular cyclization of 2-aminobenzoylacetyl-coenzyme A. Overall, our data suggest that PqsE promotes the efficiency of alkylquinolone signal molecule biosynthesis in P. aeruginosa and balances the levels of secondary metabolites deriving from the alkylquinolone biosynthetic pathway. << Less
Chem. Biol. 22:611-618(2015) [PubMed] [EuropePMC]
This publication is cited by 3 other entries.
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Dissecting the multiple roles of PqsE in Pseudomonas aeruginosa virulence by discovery of small tool compounds.
Zender M., Witzgall F., Drees S.L., Weidel E., Maurer C.K., Fetzner S., Blankenfeldt W., Empting M., Hartmann R.W.
Pseudomonas aeruginosa uses quorum sensing (QS) as a cell-to-cell communication system to orchestrate the expression of virulence determinants. The biosynthesis of the important Pseudomonas quinolone signal (PQS) requires the pqsABCDE operon. Here, PqsE acts as a pathway-specific thioesterase, but ... >> More
Pseudomonas aeruginosa uses quorum sensing (QS) as a cell-to-cell communication system to orchestrate the expression of virulence determinants. The biosynthesis of the important Pseudomonas quinolone signal (PQS) requires the pqsABCDE operon. Here, PqsE acts as a pathway-specific thioesterase, but it also contributes to the regulation of bacterial virulence via an unknown mechanism. In this manuscript, we report the discovery of PqsE inhibitors as tool compounds to gain further insights into its different functions. Differential scanning fluorimetry (DSF) was used to screen a fragment library, and isothermal titration calorimetry (ITC) was employed as a secondary filter. As proven by X-ray crystallography, hit molecules bound to the active center inhibiting PqsE's thioesterase activity in cell-based and in vitro assays. Notably, the ligands did not affect the levels of the PqsE-regulated virulence factor pyocyanin. These findings indicate that the regulatory function of PqsE is not linked to its thioesterase activity and must be encoded outside of the active center. This study highlights the potential of fragment-based screening for the discovery of tool compounds. This approach provided novel insight into complex biological systems, which could not be obtained by knockout studies. << Less