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Tripping up Trp: Modification of protein tryptophan residues by reactive oxygen species, modes of detection, and biological consequences
Open accessAbstract
Proteins comprise a majority of the dry weight of a cell, rendering them a major target for oxidative modification. Oxidation of proteins can result in significant alterations in protein molecular mass such as breakage of the polypeptide backbone and/or polymerization of monomers into dimers, multimers, and sometimes insoluble aggregates. Protein oxidation can also result in structural changes to amino acid residue side chains, conversions that have only a modest effect on protein size but can have widespread consequences for protein function. There are a wide range of rate constants for amino acid reactivity, with cysteine, methionine, tyrosine, phenylalanine, and tryptophan having the highest rate constants with commonly encountered biological oxidants. Free tryptophan and tryptophan protein residues react at a diffusion-limited rate with hydroxyl radical and also have high rate constants for reactions with singlet oxygen and ozone. Although oxidation of proteins in general and tryptophan residues specifically can have effects detrimental to the health of cells and organisms, some modifications are neutral, whereas others contribute to the function of the protein in question or may act as a signal that damaged proteins need to be replaced. This review provides a brief overview of the chemical mechanisms by which tryptophan residues become oxidized, presents both the strengths and the weaknesses of some of the techniques used to detect these oxidative interactions, and discusses selected examples of the biological consequences of tryptophan oxidation in proteins from animals, plants, and microbes.
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“Trp• reacts very rapidly with O2•− with second order rate constants, k, in the range 0.7–2.2 × 109 M−1 s−1, the main initial products being hydroperoxides, in almost quantitative yields [145,146,147,148,149,150,151], Figure 56.”
From Superoxide Anion Chemistry—Its Role at the Core of the Innate Immunity (2023) · cites this paper as [145]
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Metadata
- Authors
- Ehrenshaft, M., Deterding, L. J., & Mason, R. P.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Ehrenshaft, Marilyn
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-12
- Volume
- 89
- Pages
- 220-228
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC4684788
- OpenAlex
- W2187856084
- Cited by
- 158
- References
- 95
- Citations by year
- 2026: 16 · 2025: 13 · 2024: 15 · 2023: 20 · 2022: 16 · 2021: 22 · 2020: 15 · 2019: 15 · 2018: 14 · 2017: 6 · 2016: 6
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Environmental Health Sciences
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- tryptophan oxidation, protein oxidative modification, reactive oxygen species, hydroxyl radicals, singlet oxygen, ozone, protein aggregation, protein misfolding, protein function
- MeSH terms
- Animals, Humans, Oxidation-Reduction, Proteins, Mass Spectrometry, Tryptophan, Reactive Oxygen Species
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