Novel Inhibitor of E. coli DNA Adenine Methyltransferase (Ecodam)
Abstract:EcoDam is an adenine-N6 DNA methyltransferase
that methylates the GATC sites in the Escherichia coli genome.
DNA-adenine methylation is not present in higher eukaryotes
including humans. These observations raise the possibility that dam
inhibitors may be used as anti-microbial agents. Polyphosphate
(Poly(P)) is an important metabolite and signaling molecule in
prokaryotes and eukaryotes. Here, by using gel retardation
experiments to investigate the competition of DNA binding by
EcoDam in the presence of polyphosphate, we found that Poly (P)
strongly interferes with DNA binding by EcoDam, while same
concentration of monophosphate does not. In addition, we
demonstrated that Poly (P) binding inhibits the activity of EcoDam
and our results suggest that Poly (P) led to strong inhibition of the
EcoDam catalytic activity, while monophosphate had only moderate
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