Peroxynitrite-mediated nitration of tyrosine residues in Escherichia coli glutamine synthetase mimics adenylylation: Relevance to signal transduction
Open accessAbstract
Treatment of Escherichia coli glutamine synthetase (GS) with peroxynitrite leads to nitration of some tyrosine residues and conversion of some methionine residues to methionine sulfoxide (MSOX) residues. Nitration, but not MSOX formation, is stimulated by Fe-EDTA. In the absence of Fe-EDTA, nitration of only one tyrosine residue per subunit of unadenylylated GS leads to changes in divalent cation requirement, pH-activity profile, affinity for ADP, and susceptibility to feedback inhibition by end products (tryptophan, AMP, CTP), whereas nitration of one tyrosine residue per subunit in the adenylylated GS leads to complete loss of catalytic activity. In the presence of Fe-EDTA, nitration is a more random process: nitration of five to six tyrosine residues per subunit is needed to convert unadenylylated GS to the adenylylated configuration. These results and the fact that nitration of tyrosine residues is an irreversible process serve notice that the regulatory function of proteins that undergo phosphorylation or adenylylation in signal transduction cascades might be seriously compromised by peroxynitrite-promoted nitration.
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- Authors
- Berlett, B. S., Friguet, B., Yim, M. B., Chock, P. B., & Stadtman, E. R.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Friguet, B
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-03-05
- Volume
- 93
- Issue
- 5
- Pages
- 1776-1780
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC39857
- OpenAlex
- W1970184469
- Cited by
- 171
- References
- 14
- Citations by year
- 2024: 2 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 8 · 2013: 6 · 2012: 3
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- peroxynitrite, tyrosine nitration, glutamine synthetase, adenylylation, methionine sulfoxide, Fe-EDTA, protein regulation, signal transduction, enzyme activity, product inhibition, ADP binding, Escherichia coli
- MeSH terms
- Cations, Divalent, Escherichia coli, Glutamate-Ammonia Ligase, Manganese, Methionine, Nitrates, Structure-Activity Relationship, Tyrosine, Signal Transduction
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