title: Myricetin inhibits Escherichia coli DnaB helicase but not primase.
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 K(i) of 10.0+/-0.5 microM. At physiological ATP concentration, myricetin inhibits E. coli DnaB helicase with an inhibitory concentration at 50% maximal (IC(50)) of 11.3+/-1.6 microM. In contrast, myricetin inhibited E. coli primase at least 60-fold weaker than DnaB helicase and far weaker than any other polymerase.
authors.affiliation: Department of Chemistry, University of Nebraska-Lincoln, 614 Hamilton Hall, Lincoln, NE 68588-0304, USA. mgriep1@unl.edu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Griep
authors.forename: Sheldon
authors.initials: S
authors.lastname: Blood
authors.forename: Marilynn A
authors.initials: MA
authors.lastname: Larson
authors.forename: Scott A
authors.initials: SA
authors.lastname: Koepsell
authors.forename: Steven H
authors.initials: SH
authors.lastname: Hinrichs
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000494:pharmacology; D053488:DnaB Helicases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004926:Escherichia coli / Q000201:enzymology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids; C040015:myricetin; D000255:Adenosine Triphosphate; D053488:DnaB Helicases