Abstract

Primase and DnaB helicase play central roles during DNA replication initiation and elongation. Both enzymes are drug targets because they are essential, persistent among bacterial genomes, and have different sequences than their eukaryotic equivalents. Myricetin is a ubiquitous natural product in plants that is known to inhibit a variety of DNA polymerases, RNA polymerases, reverse transcriptases, and telomerases in addition being able to inhibit kinases and helicases. We have shown that myricetin inhibits Escherichia coli DnaB helicase according to a mechanism dominated by noncompetitive behavior with a Ki of 10.0 ± 0.5 μM. At physiological ATP concentration, myricetin inhibits E. coli DnaB helicase with an inhibitory concentration at 50% maximal (IC50) of 11.3 ± 1.6 μM. In contrast, myricetin inhibited E. coli primase at least 60-fold weaker than DnaB helicase and far weaker than any other polymerase.

Original languageEnglish (US)
Pages (from-to)7203-7208
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume15
Issue number22
DOIs
StatePublished - Nov 15 2007

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Keywords

  • DNA replication
  • DnaB helicase
  • Escherichia coli
  • Myricetin
  • Primase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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