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| | <StructureSection load='6yz3' size='340' side='right'caption='[[6yz3]], [[Resolution|resolution]] 3.00Å' scene=''> | | <StructureSection load='6yz3' size='340' side='right'caption='[[6yz3]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6yz3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_aeruginosus"_(schroeter_1872)_trevisan_1885 "bacillus aeruginosus" (schroeter 1872) trevisan 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YZ3 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6YZ3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6yz3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YZ3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Q25:6-chloranyl-3-[(2-hexyl-2,3-dihydro-1,3-thiazol-4-yl)methyl]quinazolin-4-one'>Q25</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]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6z07|6z07]], [[6z17|6z17]], [[6z5k|6z5k]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=Q25:6-chloranyl-3-[(2-hexyl-2,3-dihydro-1,3-thiazol-4-yl)methyl]quinazolin-4-one'>Q25</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mvfR, DY930_15985, E4V10_05145, F3H14_28375 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=287 "Bacillus aeruginosus" (Schroeter 1872) Trevisan 1885])</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=6yz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yz3 OCA], [https://pdbe.org/6yz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yz3 RCSB], [https://www.ebi.ac.uk/pdbsum/6yz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yz3 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6yz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yz3 OCA], [http://pdbe.org/6yz3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6yz3 RCSB], [http://www.ebi.ac.uk/pdbsum/6yz3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6yz3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A1C6ZJJ6_PSEAI A0A1C6ZJJ6_PSEAI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6yz3" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6yz3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Emsley, J]] | |
| - | [[Category: Richardson, W K]] | |
| - | [[Category: Antagonist]] | |
| - | [[Category: Dna binding protein]] | |
| | [[Category: Pseudomonas aeruginosa]] | | [[Category: Pseudomonas aeruginosa]] |
| - | [[Category: Quorum sensing]] | + | [[Category: Emsley J]] |
| | + | [[Category: Richardson WK]] |
| Structural highlights
Function
A0A1C6ZJJ6_PSEAI
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Grossman S, Soukarieh F, Richardson W, Liu R, Mashabi A, Emsley J, Williams P, Camara M, Stocks MJ. Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR. Eur J Med Chem. 2020 Aug 28;208:112778. doi: 10.1016/j.ejmech.2020.112778. PMID:32927392 doi:http://dx.doi.org/10.1016/j.ejmech.2020.112778
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