A molecular target for suppression of the evolution of antibiotic resistance: inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP

J Med Chem. 2005 Aug 25;48(17):5408-11. doi: 10.1021/jm050113z.

Abstract

We report that N(6)-(1-naphthyl)-ADP inhibits the Escherichia coli RecA protein in vitro. A novel rapid screen identified it as a potent inhibitor of RecA nucleoprotein filament formation, and further characterization established it as an ATP-competitive inhibitor of RecA-catalyzed ATP hydrolysis. This and other inhibitors of RecA activities represent a new approach for understanding the molecular targets and pathways involved in the evolution of antibiotic resistance in bacteria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Naphthylamine / analogs & derivatives*
  • 1-Naphthylamine / chemical synthesis
  • 1-Naphthylamine / chemistry
  • Adenosine Diphosphate / analogs & derivatives*
  • Adenosine Diphosphate / chemical synthesis
  • Adenosine Diphosphate / chemistry
  • Adenosine Triphosphate / chemistry
  • DNA, Single-Stranded / chemistry
  • Drug Resistance, Bacterial*
  • Escherichia coli Proteins / chemistry*
  • Hydrolysis
  • Kinetics
  • Models, Molecular
  • Protein Binding
  • Rec A Recombinases / antagonists & inhibitors*
  • Rec A Recombinases / chemistry*
  • Structure-Activity Relationship

Substances

  • DNA, Single-Stranded
  • Escherichia coli Proteins
  • N(6)-(1-naphthyl)adenosine diphosphate
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • 1-Naphthylamine
  • Rec A Recombinases