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Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition()
Superoxide dismutase (EC-SOD) controls the level of superoxide in the extracellular space by catalyzing the dismutation of superoxide into hydrogen peroxide and molecular oxygen. In addition, the enzyme reacts with hydrogen peroxide in a peroxidase reaction which is known to disrupt enzymatic activi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757672/ https://www.ncbi.nlm.nih.gov/pubmed/24024135 http://dx.doi.org/10.1016/j.redox.2012.12.004 |
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author | Gottfredsen, Randi H. Larsen, Ulrike G. Enghild, Jan J. Petersen, Steen V. |
author_facet | Gottfredsen, Randi H. Larsen, Ulrike G. Enghild, Jan J. Petersen, Steen V. |
author_sort | Gottfredsen, Randi H. |
collection | PubMed |
description | Superoxide dismutase (EC-SOD) controls the level of superoxide in the extracellular space by catalyzing the dismutation of superoxide into hydrogen peroxide and molecular oxygen. In addition, the enzyme reacts with hydrogen peroxide in a peroxidase reaction which is known to disrupt enzymatic activity. Here, we show that the peroxidase reaction supports a site-specific bond cleavage. Analyses by peptide mapping and mass spectrometry shows that oxidation of Pro112 supports the cleavage of the Pro112–His113 peptide bond. Substitution of Ala for Pro112 did not inhibit fragmentation, indicating that the oxidative fragmentation at this position is dictated by spatial organization and not by side-chain specificity. The major part of EC-SOD inhibited by the peroxidase reaction was not fragmented but found to encompass oxidations of histidine residues involved in the coordination of copper (His98 and His163). These oxidations are likely to support the dissociation of copper from the active site and thus loss of enzymatic activity. Homologous modifications have also been described for the intracellular isozyme, Cu/Zn-SOD, reflecting the almost identical structures of the active site within these enzymes. We speculate that the inactivation of EC-SOD by peroxidase activity plays a role in regulating SOD activity in vivo, as even low levels of superoxide will allow for the peroxidase reaction to occur. |
format | Online Article Text |
id | pubmed-3757672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-37576722013-09-10 Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() Gottfredsen, Randi H. Larsen, Ulrike G. Enghild, Jan J. Petersen, Steen V. Redox Biol Short Communication Superoxide dismutase (EC-SOD) controls the level of superoxide in the extracellular space by catalyzing the dismutation of superoxide into hydrogen peroxide and molecular oxygen. In addition, the enzyme reacts with hydrogen peroxide in a peroxidase reaction which is known to disrupt enzymatic activity. Here, we show that the peroxidase reaction supports a site-specific bond cleavage. Analyses by peptide mapping and mass spectrometry shows that oxidation of Pro112 supports the cleavage of the Pro112–His113 peptide bond. Substitution of Ala for Pro112 did not inhibit fragmentation, indicating that the oxidative fragmentation at this position is dictated by spatial organization and not by side-chain specificity. The major part of EC-SOD inhibited by the peroxidase reaction was not fragmented but found to encompass oxidations of histidine residues involved in the coordination of copper (His98 and His163). These oxidations are likely to support the dissociation of copper from the active site and thus loss of enzymatic activity. Homologous modifications have also been described for the intracellular isozyme, Cu/Zn-SOD, reflecting the almost identical structures of the active site within these enzymes. We speculate that the inactivation of EC-SOD by peroxidase activity plays a role in regulating SOD activity in vivo, as even low levels of superoxide will allow for the peroxidase reaction to occur. Elsevier 2013-01-11 /pmc/articles/PMC3757672/ /pubmed/24024135 http://dx.doi.org/10.1016/j.redox.2012.12.004 Text en © 2013 The Authors http://creativecommons.org/licenses/BY-NC-SA/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Short Communication Gottfredsen, Randi H. Larsen, Ulrike G. Enghild, Jan J. Petersen, Steen V. Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() |
title | Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() |
title_full | Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() |
title_fullStr | Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() |
title_full_unstemmed | Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() |
title_short | Hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() |
title_sort | hydrogen peroxide induce modifications of human extracellular superoxide dismutase that results in enzyme inhibition() |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757672/ https://www.ncbi.nlm.nih.gov/pubmed/24024135 http://dx.doi.org/10.1016/j.redox.2012.12.004 |
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