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The mechanism of action of inhibitors of bacterial two-component signal transduction systems

Academic Article
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Overview

authors

  • Stephenson, K.
  • Yamaguchi, Y.
  • Hoch, James

publication date

  • December 2000

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Two-component signal transduction systems allow bacteria to sense and respond rapidly to changes in their environment leading to specific gene activation or repression. These two-component systems are integral in the ability of pathogenic bacteria to mount and establish a successful infection within the host and, consequently, have been recognized as targets for new anti-microbial agents. In this paper, we define the site and mechanism of action of several previously identified inhibitors of bacterial two-component systems. We show that the most potent inhibitors target the carboxyl-terminal catalytic domain of the sensor kinase and exert their affect by causing structural alterations of the kinase leading to aggregation. Recognition of this phenomenon has important implications for the development of novel inhibitors of two-component systems and should facilitate the rapid identification and elimination of compounds with nonspecific affects from medicinal chemistry drug discovery programs.

subject areas

  • Anti-Bacterial Agents
  • Bacillus subtilis
  • Bacterial Proteins
  • Dimerization
  • Enzyme Inhibitors
  • Guanidines
  • Ofloxacin
  • Protein Kinases
  • Salicylanilides
  • Second Messenger Systems
  • Signal Transduction
  • Trityl Compounds
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M006633200

PubMed ID

  • 10978341
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Additional Document Info

start page

  • 38900

end page

  • 38904

volume

  • 275

issue

  • 49

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