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  • Chemical proteomics reveals new targets of cysteine sulfinic acid reductase.

Chemical proteomics reveals new targets of cysteine sulfinic acid reductase.

Nature chemical biology (2018-09-05)
Salma Akter, Ling Fu, Youngeun Jung, Mauro Lo Conte, J Reed Lawson, W Todd Lowther, Rui Sun, Keke Liu, Jing Yang, Kate S Carroll
ABSTRACT

Cysteine sulfinic acid or S-sulfinylation is an oxidative post-translational modification (OxiPTM) that is known to be involved in redox-dependent regulation of protein function but has been historically difficult to analyze biochemically. To facilitate the detection of S-sulfinylated proteins, we demonstrate that a clickable, electrophilic diazene probe (DiaAlk) enables capture and site-centric proteomic analysis of this OxiPTM. Using this workflow, we revealed a striking difference between sulfenic acid modification (S-sulfenylation) and the S-sulfinylation dynamic response to oxidative stress, which is indicative of different roles for these OxiPTMs in redox regulation. We also identified >55 heretofore-unknown protein substrates of the cysteine sulfinic acid reductase sulfiredoxin, extending its function well beyond those of 2-cysteine peroxiredoxins (2-Cys PRDX1-4) and offering new insights into the role of this unique oxidoreductase as a central mediator of reactive oxygen species-associated diseases, particularly cancer. DiaAlk therefore provides a novel tool to profile S-sulfinylated proteins and study their regulatory mechanisms in cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-oxDJ-1 Antibody (Cys106), clone M149, clone M149, from mouse
Sigma-Aldrich
(2R)-2-{[(9H-Fluoren-9-ylmethoxy)carbonyl]amino}-3-sulfanylpropanoic acid
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Sigma-Aldrich
4-Nitrobenzenediazonium tetrafluoroborate, 97%
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Catalase−polyethylene glycol, lyophilized powder, ~40,000 units/mg protein