6z07: Difference between revisions
New page: '''Unreleased structure''' The entry 6z07 is ON HOLD Authors: Richardson, W.K., Emsley, J. Description: PqsR (MvfR) in complex with antagonist 12 Category: Unreleased Structures [[... |
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==PqsR (MvfR) in complex with antagonist 12== | |||
<StructureSection load='6z07' size='340' side='right'caption='[[6z07]], [[Resolution|resolution]] 2.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6z07]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_UCBPP-PA14 Pseudomonas aeruginosa UCBPP-PA14]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z07 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]] 2.95Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=Q4E:3-[(2-~{tert}-butyl-1,3-thiazol-4-yl)methyl]-6-chloranyl-quinazolin-4-one'>Q4E</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=6z07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z07 OCA], [https://pdbe.org/6z07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z07 RCSB], [https://www.ebi.ac.uk/pdbsum/6z07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z07 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A0H2Z7A6_PSEAB A0A0H2Z7A6_PSEAB] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Rising numbers of cases of multidrug- and extensively drug-resistant Pseudomonas aeruginosa over recent years have created an urgent need for novel therapeutic approaches to cure potentially fatal infections. One such approach is virulence attenuation where anti-virulence compounds, designed to reduce pathogenicity without affording bactericidal effects, are employed to treat infections. P. aeruginosa uses the pqs quorum sensing (QS) system, to coordinate the expression of a large number of virulence determinants as well as bacterial-host interactions and hence represents an excellent anti-virulence target. We report the synthesis and identification of a new series of thiazole-containing quinazolinones capable of inhibiting PqsR, the transcriptional regulator of the pqs QS system. The compounds demonstrated high potency (IC50 < 300 nM) in a whole-cell assay, using a mCTX:PpqsA-lux-based bioreporter for the P. aeruginosa PAO1-L and PA14 strains. Structural evaluation defined the binding modes of four analogues in the ligand-binding domain of PqsR through X-ray crystallography. Further work showed the ability of 6-chloro-3((2-pentylthiazol-4-yl)methyl)quinazolin-4(3H)-one (18) and 6-chloro-3((2-hexylthiazol-4-yl)methyl)quinazolin-4(3H)-one (19) to attenuate production of the PqsR-regulated virulence factor pyocyanin. Compounds 18 and 19 showed a low cytotoxic profile in the A549 human epithelial lung cell line making them suitable candidates for further pre-clinical evaluation. | |||
Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR.,Grossman S, Soukarieh F, Richardson W, Liu R, Mashabi A, Emsley J, Williams P, Camara M, Stocks MJ Eur J Med Chem. 2020 Aug 28;208:112778. doi: 10.1016/j.ejmech.2020.112778. PMID:32927392<ref>PMID:32927392</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Emsley | <div class="pdbe-citations 6z07" style="background-color:#fffaf0;"></div> | ||
[[Category: Richardson | |||
==See Also== | |||
*[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Pseudomonas aeruginosa UCBPP-PA14]] | |||
[[Category: Emsley J]] | |||
[[Category: Richardson WK]] | |||