6euz: Difference between revisions

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-'''Unreleased structure'''
-The entry 6euz is ON HOLD  until Paper Publication
+==The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (MK37)==
+<StructureSection load='6euz' size='340' side='right' caption='[[6euz]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6euz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacterium_monocytogenes_hominis"_nyfeldt_1932 "bacterium monocytogenes hominis" nyfeldt 1932]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EUZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EUZ FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C8Q:(3~{R})-8-methoxy-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic+acid'>C8Q</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f1r|5f1r]], [[6eut|6eut]], [[6euu|6euu]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">prfA, AJN46_04535, BWI22_01025 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1639 "Bacterium monocytogenes hominis" Nyfeldt 1932])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6euz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6euz OCA], [http://pdbe.org/6euz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6euz RCSB], [http://www.ebi.ac.uk/pdbsum/6euz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6euz ProSAT]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Listeria monocytogenes is a bacterial pathogen that controls much of its virulence through the transcriptional regulator PrfA. In this study, we describe structure-guided design and synthesis of a set of PrfA inhibitors based on ring-fused 2-pyridone heterocycles. Our most effective compound decreased virulence factor expression, reduced bacterial uptake into eukaryotic cells, and improved survival of chicken embryos infected with L. monocytogenes compared to previously identified compounds. Crystal structures identified an intraprotein "tunnel" as the main inhibitor binding site (AI), where the compounds participate in an extensive hydrophobic network that restricts the protein's ability to form functional DNA-binding helix-turn-helix (HTH) motifs. Our studies also revealed a hitherto unsuspected structural plasticity of the HTH motif. In conclusion, we have designed 2-pyridone analogues that function as site-AI selective PrfA inhibitors with potent antivirulence properties.
-Authors: Begum, A., Hall, M., Grundstrom, C., Kulen, M., Lindgren, M., Johansson, J., Almqvist, F., Sauer, U.H., Sauer-Eriksson, A.E.
+Structure-Based Design of Inhibitors Targeting PrfA, the Master Virulence Regulator of Listeria monocytogenes.,Kulen M, Lindgren M, Hansen S, Cairns AG, Grundstrom C, Begum A, van der Lingen I, Brannstrom K, Hall M, Sauer UH, Johansson J, Sauer-Eriksson AE, Almqvist F J Med Chem. 2018 Apr 27. doi: 10.1021/acs.jmedchem.8b00289. PMID:29667825<ref>PMID:29667825</ref>
-Description: The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (MK37)
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Johansson, J]]
+<div class="pdbe-citations 6euz" style="background-color:#fffaf0;"></div>
-[[Category: Sauer-Eriksson, A.E]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Bacterium monocytogenes hominis nyfeldt 1932]]
+[[Category: Almqvist, F]]
+[[Category: Begum, A]]
 [[Category: Grundstrom, C]]
 [[Category: Hall, M]]
-[[Category: Sauer, U.H]]
+[[Category: Johansson, J]]
-[[Category: Begum, A]]
+[[Category: Kulen, M]]
 [[Category: Lindgren, M]]
-[[Category: Kulen, M]]
+[[Category: Sauer, U H]]
-[[Category: Almqvist, F]]
+[[Category: Sauer-Eriksson, A E]]
+[[Category: 2-pyridone]]
+[[Category: Dna binding]]
+[[Category: Dna binding protein]]
+[[Category: Drug design]]
+[[Category: Listeria monocytogene]]
+[[Category: Transcription regulator]]