5f1r: Difference between revisions
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==The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (C10)== | ==The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (C10)== | ||
<StructureSection load='5f1r' size='340' side='right' caption='[[5f1r]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='5f1r' size='340' side='right'caption='[[5f1r]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5f1r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F1R OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[5f1r]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F1R OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F1R FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=42O:(3~{R})-8-CYCLOPROPYL-7-(NAPHTHALEN-1-YLMETHYL)-5-OXIDANYLIDENE-2,3-DIHYDRO-[1,3]THIAZOLO[3,2-A]PYRIDINE-3-CARBOXYLIC+ACID'>42O</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=42O:(3~{R})-8-CYCLOPROPYL-7-(NAPHTHALEN-1-YLMETHYL)-5-OXIDANYLIDENE-2,3-DIHYDRO-[1,3]THIAZOLO[3,2-A]PYRIDINE-3-CARBOXYLIC+ACID'>42O</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2beo|2beo]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2beo|2beo]]</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5f1r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f1r OCA], [http://pdbe.org/5f1r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f1r RCSB], [http://www.ebi.ac.uk/pdbsum/5f1r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f1r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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</div> | </div> | ||
<div class="pdbe-citations 5f1r" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5f1r" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Listeriolysin positive regulatory factor A|Listeriolysin positive regulatory factor A]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: ALmqvist, F]] | [[Category: ALmqvist, F]] | ||
[[Category: Andersson, C]] | [[Category: Andersson, C]] | ||
Revision as of 10:55, 29 April 2020
The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (C10)The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (C10)
Structural highlights
Function[PRFA_LISMO] Positively regulates expression of listeriolysin, of 1-phosphadidylinositol phosphodiesterase (PI-PLC) and other virulence factors. Publication Abstract from PubMedThe transcriptional activator PrfA, a member of the Crp/Fnr family, controls the expression of some key virulence factors necessary for infection by the human bacterial pathogen Listeria monocytogenes. Phenotypic screening identified ring-fused 2-pyridone molecules that at low micromolar concentrations attenuate L. monocytogenes cellular uptake by reducing the expression of virulence genes. These inhibitors bind the transcriptional regulator PrfA and decrease its affinity for the consensus DNA-binding site. Structural characterization of this interaction revealed that one of the ring-fused 2-pyridones, compound 1, binds at two separate sites on the protein: one within a hydrophobic pocket or tunnel, located between the C- and N-terminal domains of PrfA, and the second in the vicinity of the DNA-binding helix-turn-helix motif. At both sites the compound interacts with residues important for PrfA activation and helix-turn-helix formation. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes. Attenuating Listeria monocytogenes Virulence by Targeting the Regulatory Protein PrfA.,Good JA, Andersson C, Hansen S, Wall J, Krishnan KS, Begum A, Grundstrom C, Niemiec MS, Vaitkevicius K, Chorell E, Wittung-Stafshede P, Sauer UH, Sauer-Eriksson AE, Almqvist F, Johansson J Cell Chem Biol. 2016 Mar 17;23(3):404-14. doi: 10.1016/j.chembiol.2016.02.013. PMID:26991105[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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