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Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 41839Article in journal (Refereed) Published
Abstract [en]

The alarmone nucleotide (p) ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence, making (p) ppGpp-mediated signaling a promising target for development of antibacterials. Although ppGpp itself is an activator of the ribosome-associated ppGpp synthetase RelA, several ppGpp mimics have been developed as RelA inhibitors. However promising, the currently available ppGpp mimics are relatively inefficient, with IC50 in the sub-mM range. In an attempt to identify a potent and specific inhibitor of RelA capable of abrogating (p) ppGpp production in live bacterial cells, we have tested a targeted nucleotide library using a biochemical test system comprised of purified Escherichia coli components. While none of the compounds fulfilled this aim, the screen has yielded several potentially useful molecular tools for biochemical and structural work.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017. Vol. 7, 41839
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-132129DOI: 10.1038/srep41839ISI: 000393552300001PubMedID: 28157202OAI: oai:DiVA.org:umu-132129DiVA: diva2:1080318
Available from: 2017-03-09 Created: 2017-03-09 Last updated: 2017-03-09Bibliographically approved

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Jimmy, SteffiVarik, ValloShingler, VictoriaHauryliuk, Vasili
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Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)Department of Molecular Biology (Faculty of Science and Technology)
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Scientific Reports
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CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
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  • sv-SE
  • Other locale
More languages
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