Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability

Karimi, Maryam; Ignasiak, Marta T.; Chan, Bun; Croft, Anna K.; Radom, Leo; Schiesser, Carl H.; Pattison, David I.; Davies, Michael J.

Abstract

© 2016 The Author(s). Disulfide bonds play a key role in stabilizing protein structures, with disruption strongly associated with loss of protein function and activity. Previous data have suggested that disulfides show only modest reactivity with oxidants. In the current study, we report kinetic data indicating that selected disulfides react extremely rapidly, with a variation of 104 in rate constants. Five-membered ring disulfides are particularly reactive compared with acyclic (linear) disulfides or six-membered rings. Particular disulfides in proteins also show enhanced reactivity. This variation occurs with multiple oxidants and is shown to arise from favorable electrostatic stabilization of the incipient positive charge on the sulfur reaction center by remote groups, or by the neighboring sulfur for conformations in which the orbitals are suitably aligned. Controlling these factors should allow the design of efficient scavengers and high-stability proteins. These data are consistent with selective oxidative damage to particular disulfides, including those in some proteins.

Citation

Karimi, M., Ignasiak, M. T., Chan, B., Croft, A. K., Radom, L., Schiesser, C. H., …Davies, M. J. (2016). Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability. Scientific Reports, 6(1), Article 38572. https://doi.org/10.1038/srep38572

• Journal Article Type: Article
• Acceptance Date: Nov 9, 2016
• Online Publication Date: Dec 12, 2016
• Publication Date: Dec 12, 2016
• Deposit Date: Jul 26, 2017
• Publicly Available Date: Jul 26, 2017
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 1
• Article Number: 38572
• DOI: https://doi.org/10.1038/srep38572
• Public URL: https://nottingham-repository.worktribe.com/output/828857
• Publisher URL: https://www.nature.com/articles/srep38572