5F1R

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

5F1R の概要

• エントリーDOI: 10.2210/pdb5f1r/pdb
• 関連するPDBエントリー: 2BEO
• 分子名称: Listeriolysin regulatory protein, (3~{R})-8-cyclopropyl-7-(naphthalen-1-ylmethyl)-5-oxidanylidene-2,3-dihydro-[1,3]thiazolo[3,2-a]pyridine-3-carboxylic acid (3 entities in total)
• 機能のキーワード: dna binding protein, prfa, 2-pyridones, virulence
• 由来する生物種: Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55413.69

構造登録者

Begum, A.,Grundstrom, C.,Good, J.A.D.,Andersson, C.,ALmqvist, F.,Johansson, J.,Sauer, U.H.,Sauer-Eriksson, A.E. (登録日: 2015-11-30, 公開日: 2016-03-16, 最終更新日: 2024-01-10)

主引用文献

Good, J.A.,Andersson, C.,Hansen, S.,Wall, J.,Krishnan, K.S.,Begum, A.,Grundstrom, C.,Niemiec, M.S.,Vaitkevicius, K.,Chorell, E.,Wittung-Stafshede, P.,Sauer, U.H.,Sauer-Eriksson, A.E.,Almqvist, F.,Johansson, J.
Attenuating Listeria monocytogenes Virulence by Targeting the Regulatory Protein PrfA.
Cell Chem Biol, 23:404-414, 2016

PubMed Abstract: 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.

PubMed: 26991105
DOI: 10.1016/j.chembiol.2016.02.013

実験手法

X-RAY DIFFRACTION (2.25 Å)