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

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

In: Scientific Reports, Vol. 6, 38572, 12.12.2016.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Karimi, M, Ignasiak, MT, Chan, B, Croft, AK, Radom, L, Schiesser, CH, Pattison, DI & Davies, MJ 2016, 'Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability', Scientific Reports, vol. 6, 38572. https://doi.org/10.1038/srep38572

APA

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

Vancouver

Karimi M, Ignasiak MT, Chan B, Croft AK, Radom L, Schiesser CH et al. Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability. Scientific Reports. 2016 Dec 12;6. 38572. https://doi.org/10.1038/srep38572

Author

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. In: Scientific Reports. 2016 ; Vol. 6.

Bibtex

@article{5c6cc89760414d0e95fe23fa54faf619,
title = "Reactivity of disulfide bonds is markedly affected by structure and environment: implications for protein modification and stability",
abstract = "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 10(4) 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.",
author = "Maryam Karimi and Ignasiak, {Marta T} and Bun Chan and Croft, {Anna K} and Leo Radom and Schiesser, {Carl H} and Pattison, {David I} and Davies, {Michael J}",
year = "2016",
month = dec,
day = "12",
doi = "10.1038/srep38572",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Reactivity of disulfide bonds is markedly affected by structure and environment

T2 - implications for protein modification and stability

AU - Karimi, Maryam

AU - Ignasiak, Marta T

AU - Chan, Bun

AU - Croft, Anna K

AU - Radom, Leo

AU - Schiesser, Carl H

AU - Pattison, David I

AU - Davies, Michael J

PY - 2016/12/12

Y1 - 2016/12/12

N2 - 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 10(4) 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.

AB - 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 10(4) 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.

U2 - 10.1038/srep38572

DO - 10.1038/srep38572

M3 - Journal article

C2 - 27941824

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 38572

ER -

ID: 172849790