Early modification of cytochrome c by hydrogen peroxide triggers its fast degradation
| Autor: | Tibor Kožár, Nataša Tomášková, Petr Man, Martina Petrenčáková, Daniel Jancura, Petr Novák, Ghazaleh Yassaghi, Erik Sedlák |
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| Rok vydání: | 2021 |
| Předmět: |
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Molecular Protein Conformation Radical Respiratory chain 02 engineering and technology Molecular Dynamics Simulation Biochemistry Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Structural Biology Animals Horses Tyrosine Hydrogen peroxide Molecular Biology Heme 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species biology Protein Stability Cytochrome c Circular Dichroism Cytochromes c General Medicine Hydrogen Peroxide 021001 nanoscience & nanotechnology Amino acid chemistry Proteolysis biology.protein Biophysics 0210 nano-technology Oxidation-Reduction |
| Zdroj: | International Journal of Biological Macromolecules |
| ISSN: | 0141-8130 |
| DOI: | 10.1016/j.ijbiomac.2021.01.189 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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