Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 24 October 2003:
Vol. 302. no. 5645, pp. 650 - 654
DOI: 10.1126/science.1087526
Prev | Table of Contents | Next

Reports

A New Class of Bacterial RNA Polymerase Inhibitor Affects Nucleotide Addition

Irina Artsimovitch,1* Clement Chu,2 A. Simon Lynch,2{dagger} Robert Landick1{dagger}

RNA polymerase (RNAP) is the central enzyme of gene expression. Despite availability of crystal structures, details of its nucleotide addition cycle remain obscure. We describe bacterial RNAP inhibitors (the CBR703 series) whose properties illuminate this mechanism. These compounds inhibit known catalytic activities of RNAP (nucleotide addition, pyrophosphorolysis, and Gre-stimulated transcript cleavage) but not translocation of RNA or DNA when translocation is uncoupled from catalysis. CBR703-resistance substitutions occur on an outside surface of RNAP opposite its internal active site. We propose that CBR703 compounds inhibit nucleotide addition allosterically by hindering movements of active site structures that are linked to the CBR703 binding site through a bridge helix.

1 Department of Bacteriology, University of Wisconsin, Madison, WI 53706, USA.
2 Cumbre Inc., 1502 Viceroy Drive, Dallas, TX 75235, USA.

* Present address: Department of Microbiology, Ohio State University, Columbus, OH 43210, USA.

{dagger} To whom correspondence should be addressed. E-mail: simon.lynch{at}cumbre.net (A.S.L.); landick{at}bact.wisc.edu (R.L.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A Novel Indole Compound That Inhibits Pseudomonas aeruginosa Growth by Targeting MreB Is a Substrate for MexAB-OprM.
G. T. Robertson, T. B. Doyle, Q. Du, L. Duncan, K. E. Mdluli, and A. S. Lynch (2007)
J. Bacteriol. 189, 6870-6881
   Abstract »    Full Text »    PDF »
Allosteric control of the RNA polymerase by the elongation factor RfaH.
V. Svetlov, G. A. Belogurov, E. Shabrova, D. G. Vassylyev, and I. Artsimovitch (2007)
Nucleic Acids Res. 35, 5694-5705
   Abstract »    Full Text »    PDF »
In Vitro Activities of Different Inhibitors of Bacterial Transcription against Staphylococcus epidermidis Biofilm.
P. Villain-Guillot, M. Gualtieri, L. Bastide, and J.-P. Leonetti (2007)
Antimicrob. Agents Chemother. 51, 3117-3121
   Abstract »    Full Text »    PDF »
Kinetic Investigation of Escherichia coli RNA Polymerase Mutants That Influence Nucleotide Discrimination and Transcription Fidelity.
S. F. Holmes, T. J. Santangelo, C. K. Cunningham, J. W. Roberts, and D. A. Erie (2006)
J. Biol. Chem. 281, 18677-18683
   Abstract »    Full Text »    PDF »
Novel synthetic molecules targeting the bacterial RNA polymerase assembly.
E. Andre, L. Bastide, S. Michaux-Charachon, A. Gouby, P. Villain-Guillot, J. Latouche, A. Bouchet, M. Gualtieri, and J.-P. Leonetti (2006)
J. Antimicrob. Chemother. 57, 245-251
   Abstract »    Full Text »    PDF »
Molecular Genetic and Structural Modeling Studies of Staphylococcus aureus RNA Polymerase and the Fitness of Rifampin Resistance Genotypes in Relation to Clinical Prevalence.
A. J. O'Neill, T. Huovinen, C. W. G. Fishwick, and I. Chopra (2006)
Antimicrob. Agents Chemother. 50, 298-309
   Abstract »    Full Text »    PDF »
Remote Site Control of an Active Site Fidelity Checkpoint in a Viral RNA-dependent RNA Polymerase.
J. J. Arnold, M. Vignuzzi, J. K. Stone, R. Andino, and C. E. Cameron (2005)
J. Biol. Chem. 280, 25706-25716
   Abstract »    Full Text »    PDF »
{alpha}-Amanitin Blocks Translocation by Human RNA Polymerase II.
X. Q. Gong, Y. A. Nedialkov, and Z. F. Burton (2004)
J. Biol. Chem. 279, 27422-27427
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)