Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability
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 sele...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2016
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| Online Access: | https://eprints.nottingham.ac.uk/44425/ |
| _version_ | 1848796914462490624 |
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| author | Karimi, Maryam Ignasiak, Marta T. Chan, Bun Croft, Anna K. Radom, Leo Schiesser, Carl H. Pattison, David I. Davies, Michael J. |
| author_facet | Karimi, Maryam Ignasiak, Marta T. Chan, Bun Croft, Anna K. Radom, Leo Schiesser, Carl H. Pattison, David I. Davies, Michael J. |
| author_sort | Karimi, Maryam |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 highstability proteins. These data are consistent with selective oxidative damage to particular disulfides, including those in some proteins. |
| first_indexed | 2025-11-14T19:55:33Z |
| format | Article |
| id | nottingham-44425 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:55:33Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-444252020-05-04T18:21:19Z https://eprints.nottingham.ac.uk/44425/ 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. 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 highstability proteins. These data are consistent with selective oxidative damage to particular disulfides, including those in some proteins. Nature Publishing Group 2016-11-12 Article PeerReviewed Karimi, Maryam, Ignasiak, Marta T., Chan, Bun, Croft, Anna K., Radom, Leo, Schiesser, Carl H., Pattison, David I. and Davies, Michael J. (2016) Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability. Scientific Reports, 6 (1). p. 38572. ISSN 2045-2322 https://www.nature.com/articles/srep38572 doi:10.1038/srep38572 doi:10.1038/srep38572 |
| spellingShingle | Karimi, Maryam Ignasiak, Marta T. Chan, Bun Croft, Anna K. Radom, Leo Schiesser, Carl H. Pattison, David I. Davies, Michael J. Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability |
| title | Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability |
| title_full | Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability |
| title_fullStr | Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability |
| title_full_unstemmed | Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability |
| title_short | Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability |
| title_sort | reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability |
| url | https://eprints.nottingham.ac.uk/44425/ https://eprints.nottingham.ac.uk/44425/ https://eprints.nottingham.ac.uk/44425/ |