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Developing inhibitors to selectively target two-component and phosphorelay signal transduction systems of pathogenic microorganisms

Academic Article
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Overview

authors

  • Stephenson, K.
  • Hoch, James

publication date

  • March 2004

journal

  • Current Medicinal Chemistry  Journal

abstract

  • Two-component signal transduction systems and their expanded variants known as phosphorelays are integral elements of the virulence and antimicrobial resistance responses of a wide range of pathogenic bacteria and fungi and also regulate essential functions. As a consequence, two-component systems and phosphorelays are recognized targets for the development of novel antimicrobial agents and a number of chemically synthesized inhibitors from different chemical classes have been identified by compound library screens. However, in the majority of cases these compounds do not appear to be selective for signal transduction pathways and exert their effect by multiple mechanisms of action. The key to designing molecules to selectively disrupt signal transduction may lie with the conserved features of response regulators and the structural analysis of complexes of signaling proteins.

subject areas

  • Anti-Infective Agents
  • Drug Design
  • Drug Resistance, Microbial
  • Enzyme Inhibitors
  • Models, Molecular
  • Molecular Structure
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Protein Kinases
  • Signal Transduction
  • Virulence
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Research

keywords

  • inhibitor
  • phosphorelay
  • response regulator
  • sensor histidine kinase
  • two-component system
  • virulence
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Identity

International Standard Serial Number (ISSN)

  • 0929-8673

Digital Object Identifier (DOI)

  • 10.2174/0929867043455765

PubMed ID

  • 15032730
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Additional Document Info

start page

  • 765

end page

  • 773

volume

  • 11

issue

  • 6

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