Discovery of inhibitors of bacillus anthracis primase DnaG

Tapan Biswas, Keith D. Green, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Primase DnaG is an essential bacterial enzyme that synthesizes short ribonucleotide primers required for chromosomal DNA replication. Inhibitors of DnaG can serve as leads for development of new antibacterials and biochemical probes. We recently developed a nonradioactive in vitro primase-pyrophosphatase assay to identify and analyze DnaG inhibitors. Application of this assay to DnaG from Bacillus anthracis (Ba DnaG), a dangerous pathogen, yielded several inhibitors, which include agents with DNA intercalating properties (doxorubicin and tilorone) as well as those that do not intercalate into DNA (suramin). A polyanionic agent and inhibitor of eukaryotic primases, suramin, identified by this assay as a low-micromolar Ba DnaG inhibitor, was recently shown to be also a low-micromolar inhibitor of Mycobacterium tuberculosis DnaG (Mtb DnaG). In contrast, another low-micromolar Ba DnaG inhibitor, tilorone, is much more potent against Ba DnaG than against Mtb DnaG, despite homology between these enzymes, suggesting that DnaG can be targeted selectively.

Original languageEnglish
Pages (from-to)6905-6910
Number of pages6
JournalBiochemistry
Volume52
Issue number39
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Biochemistry

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