Jump to main content
Jump to site search

Issue 23, 2018
Previous Article Next Article

On the mechanism of spontaneous thiol–disulfide exchange in proteins

Author affiliations

Abstract

The thiol–disulfide exchange reaction in model systems and small peptides was investigated by means of a combined QM/MM metadynamics scheme. The free energy landscapes of these systems were generated, providing the structures of reactants and products with atomic detail, as well as the heights of free energy barriers (or, activation energies) opposing the spontaneous exchange. A QM/MM scheme with purely classical water turned out to be an efficient and accurate compromise solution. The calculations yielded the expected symmetric trisulfide transition state at S–S distances of 2.7 Å, interestingly, with a slight deviation from linearity at an S–S–S angle of 165°. The structure of the transition state as well as the free energy barrier were very similar for the intramolecular thiol–disulfide reactions in model peptides. While CXC disulfide bonds were found sterically unfavorable, CXXC were favored over longer-range disulfide bonds along the peptide backbone, in line with the high abundance of CXXC motifs in redox proteins.

Graphical abstract: On the mechanism of spontaneous thiol–disulfide exchange in proteins

Back to tab navigation

Supplementary files

Publication details

The article was received on 28 Feb 2018, accepted on 24 May 2018 and first published on 24 May 2018


Article type: Paper
DOI: 10.1039/C8CP01325J
Citation: Phys. Chem. Chem. Phys., 2018,20, 16222-16230
  •   Request permissions

    On the mechanism of spontaneous thiol–disulfide exchange in proteins

    M. Putzu, F. Gräter, M. Elstner and T. Kubař, Phys. Chem. Chem. Phys., 2018, 20, 16222
    DOI: 10.1039/C8CP01325J

Search articles by author

Spotlight

Advertisements