Protein Tyrosine Nitration: Selectivity, Physicochemical and Biological Consequences, Denitration, and Proteomics Methods for the Identification of Tyrosine-Nitrated Proteins
Abstract
Protein tyrosine nitration (PTN) is a post-translational modification occurring under the action of a nitrating agent. Tyrosine is modified in the 3-position of the phenolic ring through the addition of a nitro group (NO2). In the present article, we review the main nitration reactions and elucidate why nitration is not a random chemical process. The particular physical and chemical properties of 3-nitrotyrosine (e.g., pKa, spectrophotometric properties, reduction to aminotyrosine) will be discussed, and the biological consequences of PTN (e.g., modification of enzymatic activity, sensitivity to proteolytic degradation, impact on protein phosphorylation, immunogenicity and implication in disease) will be reviewed. Recent data indicate the possibility of an in vivo denitration process, which will be discussed with respect to the different reaction mechanisms that have been proposed. The second part of this review article focuses on analytical methods to determine this post-translational modification in complex proteomes, which remains a major challenge.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
On low-resolution instruments, isobaric ions from non-modified peptides can yield false-positive results, so data evaluation should be treated with caution.
“Especially on low resolution instruments, data evaluation should be treated with caution since isobaric ions from non-modified peptides can yield false-positive results [100].”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [100]
Cites
The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide
Pryor, W. A., & Squadrito, G. L. (1995) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1995.268.5.l699 · Cited by 1,511 · see citing works
Peroxynitrite reactivity with amino acids and proteins
Alvarez, B., & Radi, R. (2003) · Amino Acids · doi:10.1007/s00726-003-0018-8 · Cited by 560 · see citing works
Proteomic method identifies proteins nitrated <i>in vivo</i> during inflammatory challenge
Aulak, K. S., Miyagi, M., Yan, L., West, K. A., Massillon, D., Crabb, J. W., & Stuehr, D. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221269198 · Cited by 350 · see citing works
Factors Determining the Selectivity of Protein Tyrosine Nitration
Souza, J. M., Daikhin, E., Yudkoff, M., Raman, C. S., & Ischiropoulos, H. (1999) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1480 · Cited by 315 · see citing works
Saha, A., Goldstein, S., Cabelli, D., & Czapski, G. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00365-1 · Cited by 143 · see citing works
Cytochrome c: a catalyst and target of nitrite-hydrogen peroxide-dependent protein nitration
Castro, L., Eiserich, J. P., Sweeney, S., Radi, R., & Freeman, B. A. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.08.033 · Cited by 84 · see citing works
Mitochondria and regulated tyrosine nitration
Koeck, T., Stuehr, D. J., & Aulak, K. S. (2005) · Biochemical Society Transactions · doi:10.1042/bst0331399 · Cited by 30 · see citing works
Detection and characterization of in vivo nitration and oxidation of tryptophan residues in proteins
Bregere, C., Rebrin, I., & Sohal, R. S. (2008) · Methods in Enzymology · doi:10.1016/s0076-6879(08)01219-6 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Manganese Superoxide Dismutase: Guardian of the Powerhouse
Holley, A. K., Bakthavatchalu, V., Velez-Roman, J. M., & St. Clair, D. K. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms12107114 · Cited by 358 · see citing works
Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases
Kehm, R., Baldensperger, T., Raupbach, J., & Höhn, A. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101901 · Cited by 348 · see citing works
Daiber, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.01.032 · Cited by 347 · see citing works
Verrastro, I., Pasha, S., Jensen, K., Pitt, A., & Spickett, C. (2015) · Biomolecules · doi:10.3390/biom5020378 · Cited by 114 · see citing works
Surmeli, N. B., Litterman, N. K., Miller, A.-F., & Groves, J. T. (2010) · Journal of the American Chemical Society · doi:10.1021/ja105684w · Cited by 94 · see citing works
Tyrosine-nitrated proteins: Proteomic and bioanalytical aspects
Batthyány, C., Bartesaghi, S., Mastrogiovanni, M., Lima, A., Demicheli, V., & Radi, R. (2017) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6787 · Cited by 86 · see citing works
Nitric oxide is the primary mediator of cytotoxicity induced by GSH depletion in neuronal cells
Aquilano, K., Baldelli, S., Cardaci, S., Rotilio, G., & Ciriolo, M. R. (2011) · Journal of Cell Science · doi:10.1242/jcs.077149 · Cited by 67 · see citing works
Post translational modifications in adenovirus type 2
Bergström Lind, S., Artemenko, K. A., Elfineh, L., Zhao, Y., Bergquist, J., & Pettersson, U. (2013) · Virology · doi:10.1016/j.virol.2013.08.033 · Cited by 26 · see citing works
- Authors
- Abello, N., Kerstjens, H. A. M., Postma, D. S., & Bischoff, R.
- Affiliations
- University Medical Center Groningen (NL)
- Corresponding author
- Bischoff, Rainer
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-06-01
- Volume
- 8
- Issue
- 7
- Pages
- 3222-3238
- ISSN
- 1535-3893 (ISSN-L)
- 1535-3907
- OpenAlex
- W2126785007
- Cited by
- 359
- References
- 8
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 9 · 2023: 15 · 2022: 18 · 2021: 17 · 2020: 14 · 2019: 21 · 2018: 17 · 2017: 20 · 2016: 20 · 2015: 21 · 2014: 32 · 2013: 31 · 2012: 35
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Proteome Research (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- tyrosine nitration, nitrotyrosine, post-translational modification, nitrating agents, nitration selectivity, protein phosphorylation, protein immunogenicity, proteolysis, denitration
- MeSH terms
- Animals, Humans, Mitochondria, Models, Chemical, Nitrogen, Protein Processing, Post-Translational, Proteins, Spectrophotometry, Mass Spectrometry, Subcellular Fractions, Tetranitromethane, Tyrosine, Phenol, Peroxynitrous Acid, Proteomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
