5f1r: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
The | ==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=''> | |||
== 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://oca.weizmann.ac.il/oca-docs/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> | |||
<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://oca.weizmann.ac.il/oca-docs/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]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/PRFA_LISMO PRFA_LISMO]] Positively regulates expression of listeriolysin, of 1-phosphadidylinositol phosphodiesterase (PI-PLC) and other virulence factors. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 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<ref>PMID:26991105</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5f1r" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
[[Category: | __TOC__ | ||
</StructureSection> | |||
[[Category: ALmqvist, F]] | |||
[[Category: Andersson, C]] | [[Category: Andersson, C]] | ||
[[Category: Begum, A]] | [[Category: Begum, A]] | ||
[[Category: Sauer, U | [[Category: Good, J A.D]] | ||
[[Category: Grundstrom, C]] | |||
[[Category: Johansson, J]] | |||
[[Category: Sauer, U H]] | |||
[[Category: Sauer-Eriksson, A E]] | |||
[[Category: 2-pyridone]] | |||
[[Category: Dna binding protein]] | |||
[[Category: Prfa]] | |||
[[Category: Virulence]] | |||