title: Tripping up Trp: Modification of protein tryptophan residues by reactive oxygen species, modes of detection, and biological consequences.
abstract: 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.
authors.affiliation: Immunity, Inflammation and Disease Laboratory and National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. Electronic address: ehrensh1@niehs.nih.gov.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Ehrenshaft
authors.affiliation: Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Leesa J
authors.initials: LJ
authors.lastname: Deterding
authors.affiliation: Immunity, Inflammation and Disease Laboratory and National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000818:Animals; D006801:Humans; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; D014364:Tryptophan
keywords: Anti-NFK; Apolipoprotein; ESR; ESR spin trapping; Fluorescence; Kynurenine; Lysozyme; Mass spectrometry; MopE; N-formylkynurenine; Oxidation; Ozone; Photosynthesis; Protein; Radical; Singlet oxygen; Tryptophan; hSOD1; α-crystallin