View source for 7nbw


==Crystal structure of PqsR (MvfR) ligand-binding domain in complex with a pyridin agonist==
<StructureSection load='7nbw' size='340' side='right'caption='[[7nbw]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7nbw]] 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=7NBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NBW 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]] 2.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=U7Q:~{N}-[3-(4-fluorophenyl)prop-2-ynyl]-2-(trifluoromethyl)pyridin-4-amine'>U7Q</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=7nbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nbw OCA], [https://pdbe.org/7nbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nbw RCSB], [https://www.ebi.ac.uk/pdbsum/7nbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nbw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MVFR_PSEAE MVFR_PSEAE] Transcription regulator that plays a critical role in virulence by positively regulating the expression of multiple quorum sensing (QS)-regulated virulence factors, genes involved in protein secretion, translation, response to oxidative stress and the phnAB operon (PubMed:11724939, PubMed:27678057, PubMed:17083468). At the stationary phase, negatively autoregulates its function through cleavage and translocation to the extracellular space (PubMed:11724939).<ref>PMID:11724939</ref> <ref>PMID:17083468</ref> <ref>PMID:27678057</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A short and divergent route towards new derivatives of 2-(trifluoromethyl)pyridines as potent inverse agonists of the bacterial target PqsR against Pseudomonas aeruginosa (PA) infections is described. This Gram-negative pathogen causes severe nosocomial infections and common antibiotic treatment options are rendered ineffective due to resistance issues. Based on an earlier identified optimized hit, we conducted derivatization and rigidification attempts employing two central building blocks. The western part of the molecule is built up via a 2-(trifluoromethyl)pyridine head group equipped with a terminal alkyne. The eastern section is then introduced through aryliode motifs exploiting Sonogashira as well as Suzuki-type chemistry. Subsequent modification provided quick access to an array of compounds, allowed for deep SAR insights, and enabled to optimize the hit scaffold into a lead structure of nanomolar potency combined with favorable in vitro ADME/T features.

Divergent synthesis and biological evaluation of 2-(trifluoromethyl)pyridines as virulence-attenuating inverse agonists targeting PqsR.,Schutz C, Hodzic A, Hamed M, Abdelsamie AS, Kany AM, Bauer M, Rohrig T, Schmelz S, Scrima A, Blankenfeldt W, Empting M Eur J Med Chem. 2021 Aug 28;226:113797. doi: 10.1016/j.ejmech.2021.113797. PMID:34520957<ref>PMID:34520957</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7nbw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Pseudomonas aeruginosa PAO1]]
[[Category: Blankenfeldt W]]
[[Category: Schmelz S]]