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 104in 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.
authors.affiliation: The Heart Research Institute, 7 Eliza St, Newtown, NSW, 2042, Australia.|Faculty of Medicine, University of Sydney, NSW, 2006, Australia.
authors.forename: Maryam
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Department of Biomedical Science, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200, Denmark.
authors.forename: Marta T
authors.initials: MT
authors.lastname: Ignasiak
authors.affiliation: School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Bun
authors.initials: B
authors.lastname: Chan
authors.affiliation: Department of Chemical and Environmental Engineering, University of Nottingham, Nottingham NG7 2RD, Great Britain.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Croft
authors.affiliation: School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Leo
authors.initials: L
authors.lastname: Radom
authors.affiliation: School of Chemistry, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Carl H
authors.initials: CH
authors.lastname: Schiesser
authors.affiliation: The Heart Research Institute, 7 Eliza St, Newtown, NSW, 2042, Australia.|Faculty of Medicine, University of Sydney, NSW, 2006, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Pattison
authors.affiliation: The Heart Research Institute, 7 Eliza St, Newtown, NSW, 2042, Australia.|Faculty of Medicine, University of Sydney, NSW, 2006, Australia.|Department of Biomedical Science, Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen 2200, Denmark.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
mesh_terms: D004220:Disulfides / Q000737:chemistry*; D004583:Electrons; D006801:Humans; D006997:Hypochlorous Acid / Q000737:chemistry; D007328:Insulin / Q000737:chemistry; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*
chemical_list: D004220:Disulfides; D007328:Insulin; D011506:Proteins; D006997:Hypochlorous Acid; D007768:Lactalbumin