Functional diversity of cysteine residues in proteins and unique features of catalytic redox-active cysteines in thiol oxidoreductases

Dmitri E. Fomenko, Stefano M. Marino, Vadim N. Gladyshev

Research output: Contribution to journalShort survey

54 Scopus citations


Thiol-dependent redox systems are involved in regulation of diverse biological processes, such as response to stress, signal transduction, and protein folding. The thiol-based redox control is provided by mechanistically similar, but structurally distinct families of enzymes known as thiol oxidoreductases. Many such enzymes have been characterized, but identities and functions of the entire sets of thiol oxidoreductases in organisms are not known. Extreme sequence and structural divergence makes identification of these proteins difficult. Thiol oxidoreductases contain a redox-active cysteine residue, or its functional analog selenocysteine, in their active sites. Here, we describe computational methods for in silico prediction of thiol oxidoreductases in nucleotide and protein sequence databases and identification of their redox-active cysteines. We discuss different functional categories of cysteine residues, describe methods for discrimination between catalytic and noncatalytic and between redox and non-redox cysteine residues and highlight unique properties of the redox-active cysteines based on evolutionary conservation, secondary and three-dimensional structures, and sporadic replacement of cysteines with catalytically superior selenocysteine residues.

Original languageEnglish (US)
Pages (from-to)228-235
Number of pages8
JournalMolecules and Cells
Issue number3
StatePublished - Sep 30 2008



  • Cysteine
  • Redox
  • Selenocysteine
  • Thiol oxidoreductase
  • Thioredoxin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this