6tpr: Difference between revisions

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-'''Unreleased structure'''
-The entry 6tpr is ON HOLD
+==PqsR (MvfR) bound to inhibitory compound 40==
+<StructureSection load='6tpr' size='340' side='right'caption='[[6tpr]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6tpr]] 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=6TPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TPR 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]] 3.2&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NV5:2-[(5-methyl-[1,2,4]triazino[5,6-b]indol-3-yl)sulfanyl]-~{N}-(4-pyridin-2-yloxyphenyl)ethanamide'>NV5</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=6tpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6tpr OCA], [https://pdbe.org/6tpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6tpr RCSB], [https://www.ebi.ac.uk/pdbsum/6tpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6tpr ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/A0A0H2Z7A6_PSEAB A0A0H2Z7A6_PSEAB]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Current treatments for Pseudomonas aeruginosa infections are becoming less effective because of the increasing rates of multi-antibiotic resistance. Pharmacological targeting of virulence through inhibition of quorum sensing (QS) dependent virulence gene regulation has considerable therapeutic potential. In P. aeruginosa, the pqs QS system regulates the production of multiple virulence factors as well as biofilm maturation and is a promising approach for developing antimicrobial adjuvants for combatting drug resistance. In this work, we report the hit optimisation for a series of potent novel inhibitors of PqsR, a key regulator of the pqs system, bearing a 2-((5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio) acetamide scaffold. The initial hit compound 7 (PAO1-L IC50 0.98 +/- 0.02 muM, PA14 inactive at 10 muM) was obtained through a virtual screening campaign performed on the PqsR ligand binding domain using the University of Nottingham Managed Chemical Compound Collection. Hit optimisation gave compounds with enhanced potency against strains PAO1-L and PA14, evaluated using P. aeruginosa pqs-based QS bioreporter assays. Compound 40 (PAO1-L IC50 0.25 +/- 0.12 muM, PA14 IC50 0.34 +/- 0.03 muM) is one of the most potent PqsR antagonists reported showing significant inhibition of P. aeruginosa pyocyanin production and pqs system signaling in both planktonic cultures and biofilms. The co-crystal structure of 40 with the PqsR ligand binding domain revealed the specific binding interactions occurring between inhibitor and this key regulatory protein.
-Authors: Richardson, W.K., Emsley, J.
+Hit Identification of New Potent PqsR Antagonists as Inhibitors of Quorum Sensing in Planktonic and Biofilm Grown Pseudomonas aeruginosa.,Soukarieh F, Liu R, Romero M, Roberston SN, Richardson W, Lucanto S, Oton EV, Qudus NR, Mashabi A, Grossman S, Ali S, Sou T, Kukavica-Ibrulj I, Levesque RC, Bergstrom CAS, Halliday N, Mistry SN, Emsley J, Heeb S, Williams P, Camara M, Stocks MJ Front Chem. 2020 May 4;8:204. doi: 10.3389/fchem.2020.00204. eCollection 2020. PMID:32432073<ref>PMID:32432073</ref>
-Description: PqsR (MvfR) bound to inhibitory compound 40
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Emsley, J]]
+<div class="pdbe-citations 6tpr" style="background-color:#fffaf0;"></div>
-[[Category: Richardson, W.K]]
+==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]]