WFRF:(Almqvist Fredrik)
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Attenuating Listeria monocytogenes virulence by targeting the regulatory protein PrfA
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- Good, James A. D., 1985- (author)
- Umeå universitet,Kemiska institutionen,Umeå Centre for Microbial Research (UCMR),Umeå University
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- Andersson, Christopher, 1987- (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR),Molekylär Infektionsmedicin, Sverige (MIMS),Umeå University
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- Hansen, Sabine (author)
- Umeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Umeå University
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- (creator_code:org_t)
- Elsevier BV, 2016
- 2016
- English.
- In: Cell chemical biology. - : Elsevier BV. - 2451-9448 .- 2451-9456. ; 23:3, s. 404-414
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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 infectivity by reducing the expression of virulence genes, without compromising bacterial growth. 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 within a hydrophobic pocket, located between the C- and N-terminal domains of PrfA, and interacts with residues important for PrfA activation. This indicates that these inhibitors maintain the DNA-binding helix-turn-helix motif of PrfA in a disordered state, thereby preventing a PrfA:DNA interaction. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- molekylärbiologi
- Molecular Biology
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- ref (subject category)
- art (subject category)
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