ArticleChemical research in toxicology2015
Site-specific, intramolecular cross-linking of Pin1 active site residues by the lipid electrophile 4-oxo-2-nonenal.
Article in Chemical research in toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- 2-Alkyl Furans Undergo Radiolytic Oxidative Protein Cross-Linking.Journal of the American Chemical Society · 2026Article
- 4-Oxo-2-Nonenal Crosslinks Vicinal Cysteine-Lysine Pairs in Cellular Proteins.Molecular & cellular proteomics : MCP · 2026Article
- Evaluation of ω-alkynyl-labeled linoleic and arachidonic acids as substrates for recombinant lipoxygenase pathway enzymes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Protein Lipoxidation: Basic Concepts and Emerging Roles.Antioxidants (Basel, Switzerland) · 2021Review
- Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction.Nature communications · 2021Article
- A Comprehensive Review on Source, Types, Effects, Nanotechnology, Detection, and Therapeutic Management of Reactive Carbonyl Species Associated with Various Chronic Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Isolevuglandins as mediators of disease and the development of dicarbonyl scavengers as pharmaceutical interventions.Pharmacology & therapeutics · 2020Review
- 4-Hydroxynonenal and 4-Oxononenal Differentially Bind to the Redox Sensor MitoNEET.Chemical research in toxicology · 2019Article
- Regulation of stress signaling pathways by protein lipoxidation.Redox biology · 2019Review
- Chemoproteomics Reveals Chemical Diversity and Dynamics of 4-Oxo-2-nonenal Modifications in Cells.Molecular & cellular proteomics : MCP · 2017Article
- Electrophilic Modification of PKM2 by 4-Hydroxynonenal and 4-Oxononenal Results in Protein Cross-Linking and Kinase Inhibition.Chemical research in toxicology · 2017Article
- Scavenging 4-Oxo-2-nonenal.Chemical research in toxicology · 2015Article
- Protein lipoxidation: Detection strategies and challenges.Redox biology · 2015Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Products of oxidative damage to lipids include 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE), both of which are cytotoxic electrophiles. ONE reacts more rapidly with nucleophilic amino acid side chains, resulting in covalent protein adducts, including residue-residue cross-links. Previously, we demonstrated that peptidylprolyl cis/trans isomerase A1 (Pin1) was highly susceptible to adduction by HNE and that the catalytic cysteine (Cys113) was the preferential site of modification. Here, we show that ONE also preferentially adducts Pin1 at the catalytic Cys but results in a profoundly different modification. Results from experiments using purified Pin1 incubated with ONE revealed the principal product to be a Cys-Lys pyrrole-containing cross-link between the side chains of Cys113 and Lys117. In vitro competition assays between HNE and ONE demonstrate that ONE reacts more rapidly than HNE with Cys113. Exposure of RKO cells to alkynyl-ONE (aONE) followed by copper-mediated click chemistry and streptavidin purification revealed that Pin1 is also modified by ONE in cells. Analysis of the Pin1 crystal structure reveals that Cys113 and Lys117 are oriented toward each other in the active site, facilitating formation of an ONE cross-link.
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