A molecular target for suppression of the evolution of antibiotic resistance: inhibition of the Escherichia coli RecA protein by N(6)-(1-naphthyl)-ADP.
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.
Lee
Andrew M
AM
School of Pharmacy, Division of Medicinal Chemistry and Natural Products, University of North Carolina at Chapel Hill, CB 7360, Chapel Hill, North Carolina 27599-7360, USA.
Ross
Christian T
CT
Zeng
Bu-Bing
BB
Singleton
Scott F
SF
D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D004277:DNA, Single-Stranded / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D029968:Escherichia coli Proteins / Q000737:chemistry*; D006868:Hydrolysis; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D011938:Rec A Recombinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; C504516:N(6)-(1-naphthyl)adenosine diphosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D015057:1-Naphthylamine; D011938:Rec A Recombinases