5f1r

The Transcriptional Regulator PrfA from Listeria Monocytogenes in complex with a ring-fused 2-pyridone (C10)

spinqualitylabelsall models 5f1r, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5f1r is a 2 chain structure with sequence from Listeria monocytogenes EGD-e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Ligands: 42O Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PRFA_LISMO Positively regulates expression of listeriolysin, of 1-phosphadidylinositol phosphodiesterase (PI-PLC) and other virulence factors. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transcriptional activator 3D structures

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