Early modification of cytochrome c by hydrogen peroxide triggers its fast degradation
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
33529629
DOI
10.1016/j.ijbiomac.2021.01.189
PII: S0141-8130(21)00237-3
Knihovny.cz E-resources
- Keywords
- Oxidative damage, Protein channels, Pseudo-peroxidases, Reactive oxygen species, Suicide inactivation,
- MeSH
- Circular Dichroism MeSH
- Cytochromes c chemistry genetics metabolism MeSH
- Mass Spectrometry MeSH
- Horses MeSH
- Protein Conformation MeSH
- Models, Molecular MeSH
- Oxidation-Reduction MeSH
- Hydrogen Peroxide pharmacology MeSH
- Proteolysis MeSH
- Molecular Dynamics Simulation MeSH
- Protein Stability MeSH
- Tyrosine chemistry MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Cytochromes c MeSH
- Hydrogen Peroxide MeSH
- Tyrosine MeSH
Cytochrome c (cyt c), in addition to its function as an electron shuttle in respiratory chain, is able to perform as a pseudo-peroxidase with a critical role during apoptosis. Incubation of cyt c with an excess of hydrogen peroxide leads to a suicide inactivation of the protein, which is accompanied by heme destruction and covalent modification of numerous amino acid residues. Although steady-state reactions of cyt c with an excess of hydrogen peroxide represent non-physiological conditions, they might be used for analysis of the first-modified amino acid in in vivo. Here, we observed oxidation of tyrosine residues 67 and 74 and heme as the first modifications found upon incubation with hydrogen peroxide. The positions of the oxidized tyrosines suggest a possible migration pathway of hydrogen peroxide-induced radicals from the site of heme localization to the protein surface. Analysis of a size of folded fraction of cyt c upon limited incubation with hydrogen peroxide indicates that the early oxidation of amino acids triggers an accelerated destruction of cyt c. Position of channels from molecular dynamics simulation structures of cyt c points to a location of amino acid residues exposed to reactive oxidants that are thus more prone to covalent modification.
Department of Biophysics Faculty of Science P J Šafárik University Jesenná 5 041 54 Košice Slovakia
Institute of Microbiology BioCeV Vídeňská 1083 142 20 Prague 4 Czech Republic
References provided by Crossref.org
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