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Biological Chemistry

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Volume 396, Issue 5


Enzymatic control of cysteinyl thiol switches in proteins

Marcel Deponte
  • Corresponding author
  • Department of Parasitology, Ruprecht Karls University, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany
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/ Christopher Horst Lillig
  • Corresponding author
  • Institute for Medical Biochemistry and Molecular Biology, University Medicine, Ernst Moritz Arndt University, Ferdinand-Sauerbruch-Strasse, D-17475 Greifswald, Germany
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Published Online: 2015-01-10 | DOI: https://doi.org/10.1515/hsz-2014-0280


The spatiotemporal modification of specific cysteinyl residues in proteins has emerged as a novel concept in signal transduction. Such modifications alter the redox state of the cysteinyl thiol group, with implications for the structure and biological function of the protein. Regulatory cysteines are therefore classified as ‘thiol switches’. In this review we emphasize the relevance of enzymes for specific and efficient redox sensing, evaluate prerequisites and general properties of redox switches, and highlight mechanistic principles for toggling thiol switches. Moreover, we provide an overview of potential mechanisms for the initial formation of regulatory disulfide bonds. In brief, we address the three basic questions (i) what defines a thiol switch, (ii) which parameters confer signal specificity, and (iii) how are thiol switches oxidized?

Keywords: complementarity; disulfide; hydroperoxide; redox catalysis; redox regulation; signal transduction


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Corresponding authors: Marcel Deponte, Department of Parasitology, Ruprecht Karls University, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany, e-mail: ; and Christopher Horst Lillig, Institute for Medical Biochemistry and Molecular Biology, University Medicine, Ernst Moritz Arndt University, Ferdinand-Sauerbruch-Strasse, D-17475 Greifswald, Germany, e-mail:

Received: 2014-11-28

Accepted: 2014-12-23

Published Online: 2015-01-10

Published in Print: 2015-05-01

Citation Information: Biological Chemistry, Volume 396, Issue 5, Pages 401–413, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2014-0280.

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