View source for 7kgx


==Structure of PQS Response Protein PqsE in Complex with 4-(3-(2-methyl-2-morpholinobutyl)ureido)-N-(thiazol-2-yl)benzamide==
<StructureSection load='7kgx' size='340' side='right'caption='[[7kgx]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kgx]] is a 1 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=7KGX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KGX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#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=WE1:4-({[(2R)-2-methyl-2-(morpholin-4-yl)butyl]carbamoyl}amino)-N-(1,3-thiazol-2-yl)benzamide'>WE1</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=7kgx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kgx OCA], [https://pdbe.org/7kgx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kgx RCSB], [https://www.ebi.ac.uk/pdbsum/7kgx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kgx ProSAT]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pseudomonas aeruginosa is an opportunistic human pathogen that causes fatal infections. There exists an urgent need for new antimicrobial agents to combat P. aeruginosa. We conducted a screen for molecules that bind the virulence-controlling protein PqsE and characterized hit compounds for inhibition of PqsE enzymatic activity. The binding conformations of two inhibitory molecules, BB391 and BB393, were identified by crystallography, and inhibitor binding was mimicked by the substitution of PqsE residues E182 and S285 with tryptophan. Comparison of the inhibitor-mimetic mutations to the catalytically inactive PqsE D73A protein demonstrated that catalysis is not responsible for the role PqsE plays in driving virulence factor production. Rather, the PqsE E182W protein fails to interact with the quorum-sensing receptor, RhlR, and our results suggest that it is this interaction that is responsible for promoting virulence factor production in P. aeruginosa. These findings provide a new route for drug discovery efforts targeting PqsE.

Inhibitor Mimetic Mutations in the Pseudomonas aeruginosa PqsE Enzyme Reveal a Protein-Protein Interaction with the Quorum-Sensing Receptor RhlR That Is Vital for Virulence Factor Production.,Taylor IR, Paczkowski JE, Jeffrey PD, Henke BR, Smith CD, Bassler BL ACS Chem Biol. 2021 Apr 16;16(4):740-752. doi: 10.1021/acschembio.1c00049. Epub, 2021 Apr 1. PMID:33793200<ref>PMID:33793200</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7kgx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa PAO1]]
[[Category: Bassler BL]]
[[Category: Jeffrey PD]]
[[Category: Taylor IR]]