A new inhibitor of the transcription-termination factor Rho.
In this study we describe BI-K0058, a new inhibitor of the transcription-termination factor Rho belonging to a different chemical class from bicyclomycin, the only known antibiotic acting on Rho. BI-K0058 inhibits the poly(C)-dependent ATPase activity of Rho with an IC(50) of 25 microM as well as in vitro transcription-termination of two natural substrates, the Salmonella enterica hisG cistron and the f1 phage intergenic region. BI-K0058 does not affect photolabeling of Rho by ATP. The results of gel mobility shift experiments with a natural RNA substrate demonstrate that BI-K0058 inhibits the formation of the ATP-independent high affinity Rho-RNA complex.
Carrano
Lucia
L
Biosearch Italia, via R. Lepetit 34, 21040 Gerenzano, VA, Italy. lcarrano@biosearch.it
Alifano
Pietro
P
Corti
Emiliana
E
Bucci
Cecilia
C
Donadio
Stefano
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009016:Moraxella / Q000187:drug effects; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D012313:RNA / Q000187:drug effects / Q000378:metabolism; D012234:Rho Factor / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; C472591:BIK0058; D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012234:Rho Factor; D012313:RNA; D000255:Adenosine Triphosphate; C024504:bicozamycin