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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.

Authors

Maryam Karimi

Marta T. Ignasiak

Bun Chan

Leo Radom

Carl H. Schiesser

David I. Pattison

Michael J. Davies



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.

Journal Article Type Article
Publication Date Dec 12, 2016
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 6
Issue 1
Article Number 38572
APA6 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), https://doi.org/10.1038/srep38572
DOI https://doi.org/10.1038/srep38572
Publisher URL https://www.nature.com/articles/srep38572
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0







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