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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[8b4a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B4A FirstGlance]. <br>
<table><tr><td colspan='2'>[[8b4a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B4A FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=HL4:N-[(3S)-2-OXOTETRAHYDROFURAN-3-YL]BUTANAMIDE'>HL4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.06&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=HL4:N-[(3S)-2-OXOTETRAHYDROFURAN-3-YL]BUTANAMIDE'>HL4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8b4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b4a OCA], [https://pdbe.org/8b4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b4a RCSB], [https://www.ebi.ac.uk/pdbsum/8b4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b4a ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8b4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b4a OCA], [https://pdbe.org/8b4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b4a RCSB], [https://www.ebi.ac.uk/pdbsum/8b4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b4a ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/PQSE_PSEAE PQSE_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. Catalyzes the hydrolysis of the intermediate 2-aminobenzoylacetyl-CoA (2-ABA-CoA) to form 2-aminobenzoylacetate (2-ABA), the precursor of HHQ. In vitro, can also hydrolyze other substrates such as S-ethyl-acetothioacetate and acetoacetyl-CoA, but is inactive against anthraniloyl-CoA, malonyl-CoA and octanoyl-CoA (PubMed:25960261, PubMed:27082157). Beyond its thioesterase function, is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development (PubMed:27851827).<ref>PMID:25960261</ref> <ref>PMID:27082157</ref> <ref>PMID:27851827</ref>  
[https://www.uniprot.org/uniprot/PQSE_PSEAE PQSE_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. Catalyzes the hydrolysis of the intermediate 2-aminobenzoylacetyl-CoA (2-ABA-CoA) to form 2-aminobenzoylacetate (2-ABA), the precursor of HHQ. In vitro, can also hydrolyze other substrates such as S-ethyl-acetothioacetate and acetoacetyl-CoA, but is inactive against anthraniloyl-CoA, malonyl-CoA and octanoyl-CoA (PubMed:25960261, PubMed:27082157). Beyond its thioesterase function, is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development (PubMed:27851827).<ref>PMID:25960261</ref> <ref>PMID:27082157</ref> <ref>PMID:27851827</ref>  
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== Publication Abstract from PubMed ==
Pseudomonas aeruginosa is a major cause of nosocomial infections and also leads to severe exacerbations in cystic fibrosis or chronic obstructive pulmonary disease. Three intertwined quorum sensing systems control virulence of P. aeruginosa, with the rhl circuit playing the leading role in late and chronic infections. The majority of traits controlled by rhl transcription factor RhlR depend on PqsE, a dispensable thioesterase in Pseudomonas Quinolone Signal (PQS) biosynthesis that interferes with RhlR through an enigmatic mechanism likely involving direct interaction of both proteins. Here we show that PqsE and RhlR form a 2:2 protein complex that, together with RhlR agonist N-butanoyl-L-homoserine lactone (C4-HSL), solubilizes RhlR and thereby renders the otherwise insoluble transcription factor active. We determine crystal structures of the complex and identify residues essential for the interaction. To corroborate the chaperone-like activity of PqsE, we design stability-optimized variants of RhlR that bypass the need for C4-HSL and PqsE in activating PqsE/RhlR-controlled processes of P. aeruginosa. Together, our data provide insight into the unique regulatory role of PqsE and lay groundwork for developing new P. aeruginosa-specific pharmaceuticals.


Moonlighting chaperone activity of the enzyme PqsE contributes to RhlR-controlled virulence of Pseudomonas aeruginosa.,Borgert SR, Henke S, Witzgall F, Schmelz S, Zur Lage S, Hotop SK, Stephen S, Lubken D, Kruger J, Gomez NO, van Ham M, Jansch L, Kalesse M, Pich A, Bronstrup M, Haussler S, Blankenfeldt W Nat Commun. 2022 Dec 1;13(1):7402. doi: 10.1038/s41467-022-35030-w. PMID:36456567<ref>PMID:36456567</ref>
==See Also==
 
*[[Thioesterase 3D structures|Thioesterase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8b4a" style="background-color:#fffaf0;"></div>
== References ==
== References ==
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