Cysteine residues as catalysts for covalent peptide and protein modification: a role for thiyl radicals?

Schöneich, Christian

doi:10.1042/bst0391254

Cited by 15 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They are also a potential source for S -nitrosylation, S -glutathiolation, and sulfenic acid production regulation. But little is known about the in vivo role of cysteine thiyl radicals in redox signaling ( Schöneich, 2011 ).…”

Section: Cysteine-mediated Redox Signalingmentioning

confidence: 99%

Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

Wang

Branicky

Noë

et al. 2018

Journal of Cell Biology

1,376

833

View full text Add to dashboard Cite

show abstract

Section: Cysteine-mediated Redox Signalingmentioning

confidence: 99%

Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

Wang

Branicky

Noë

et al. 2018

Journal of Cell Biology

1,376

833

View full text Add to dashboard Cite

show abstract

“…In addition to the sulfur-containing amino acids, oxidation of other amino acid residues can occur but they are not readily reversible making them ill-suited for initiating rapid on/off responses to upstream signals ( Dickinson and Chang, 2011 ; Corcoran and Cotter, 2013 ). Cysteine oxidative modifications are therefore preferred for modulating signal transduction since they readily react with most ROS ( Schoneich, 2011 ) to create a range of modifications that are largely reversible.…”

Section: The Chemistry Of Cysteine Biology: Why Cells Prefer Cysteinementioning

confidence: 99%

Protein redox chemistry: post-translational cysteine modifications that regulate signal transduction and drug pharmacology

Wani¹,

Nagata²,

Murray³

2014

Front. Pharmacol.

View full text Add to dashboard Cite

The perception of reactive oxygen species has evolved over the past decade from agents of cellular damage to secondary messengers which modify signaling proteins in physiology and the disease state (e.g., cancer). New protein targets of specific oxidation are rapidly being identified. One emerging class of redox modification occurs to the thiol side chain of cysteine residues which can produce multiple chemically distinct alterations to the protein (e.g., sulfenic/sulfinic/sulfonic acid, disulfides). These post-translational modifications (PTM) are shown to affect the protein structure and function. Because redox-sensitive proteins can traffic between subcellular compartments that have different redox environments, cysteine oxidation enables a spatio-temporal control to signaling. Understanding ramifications of these oxidative modifications to the functions of signaling proteins is crucial for understanding cellular regulation as well as for informed-drug discovery process. The effects of EGFR oxidation of Cys797 on inhibitor pharmacology are presented to illustrate the principle. Taken together, cysteine redox PTM can impact both cell biology and drug pharmacology.

show abstract

“…More importantly, any radical and/ or oxidant which can generate a thiyl radical can induce irreversible protein damage through the ensuing hydrogentransfer reactions. 69 Such mechanisms may become important especially for radicals of low reactivity, which will not react with any amino acid in a protein except Cys. In vivo , such reactions may lead to protein inactivation and accelerated protein turnover.…”

Section: Discussionmentioning

confidence: 99%

Reversible Hydrogen Transfer Reactions in Thiyl Radicals From Cysteine and Related Molecules: Absolute Kinetics and Equilibrium Constants Determined by Pulse Radiolysis

2012

Self Cite

View full text Add to dashboard Cite

The mercapto group of cysteine (Cys) is a predominant target for oxidative modification, where one-electron oxidation leads to the formation of Cys thiyl radicals, CysS•. These Cys thiyl radicals enter 1,2- and 1,3-hydrogen transfer reactions, for which rate constants are reported in this paper. The products of these 1,2- and 1,3-hydrogen transfer reactions are carbon-centered radicals at position C3 (α-mercaptoalkyl radicals) and C2 (•Cα radicals) of Cys, respectively. Both processes can be monitored separately in Cys analogues such as cysteamine (CyaSH) and penicillamine (PenSH). At acidic pH, thiyl radicals from CyaSH permit only the 1,2-hydrogen transfer according to equilibrium 12, +H3NCH2CH2S• ⇌ +H3NCH2 •CH–SH, where rate constants for forward and reverse reaction are k12 ≈ 105 s−1 and k−12 ≈ 1.5 × 105s−1, respectively. In contrast, only the 1,3-hydrogen transfer is possible for thiyl radicals from PenSH according to equilibrium 14, (+H3N/CO2H)Cα–C(CH3)2–S• ⇌ (+H3N/CO2H)•Cα–C(CH3)2–SH, where rate constants for the forward and the reverse reaction are k14 = 8 × 104 s−1 and k−14 = 1.4 × 106 s−1. The •Cα radicals from PenSH and Cys have the additional opportunity for β-elimination of HS•/S•−, which proceeds with k39 ≈ (3 ± 1) × 104 s−1 from •Cα radicals from PenSH and k−34 ≈ 5 × 103 s−1 from •Cα radicals from Cys. The rate constants quantified for the 1,2- and 1,3-hydrogen transfer reactions can be used as a basis to calculate similar processes for Cys thiyl radicals in proteins, where hydrogen transfer reactions, followed by the addition of oxygen, may lead to the irreversible modification of target proteins.

show abstract

Cysteine residues as catalysts for covalent peptide and protein modification: a role for thiyl radicals?

Cited by 15 publications

References 38 publications

Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

Protein redox chemistry: post-translational cysteine modifications that regulate signal transduction and drug pharmacology

Reversible Hydrogen Transfer Reactions in Thiyl Radicals From Cysteine and Related Molecules: Absolute Kinetics and Equilibrium Constants Determined by Pulse Radiolysis

Contact Info

Product

Resources

About