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Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State
Human peroxiredoxins (Prx) are a family of antioxidant enzymes involved in a myriad of cellular functions and diseases. During the reaction with peroxides (e.g., H(2)O(2)), the typical 2-Cys Prxs change oligomeric structure between higher order (do)decamers and disulfide-linked dimers, with the hype...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230665/ https://www.ncbi.nlm.nih.gov/pubmed/34208049 http://dx.doi.org/10.3390/antiox10060946 |
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author | Forshaw, Tom E. Reisz, Julie A. Nelson, Kimberly J. Gumpena, Rajesh Lawson, J. Reed Jönsson, Thomas J. Wu, Hanzhi Clodfelter, Jill E. Johnson, Lynnette C. Furdui, Cristina M. Lowther, W. Todd |
author_facet | Forshaw, Tom E. Reisz, Julie A. Nelson, Kimberly J. Gumpena, Rajesh Lawson, J. Reed Jönsson, Thomas J. Wu, Hanzhi Clodfelter, Jill E. Johnson, Lynnette C. Furdui, Cristina M. Lowther, W. Todd |
author_sort | Forshaw, Tom E. |
collection | PubMed |
description | Human peroxiredoxins (Prx) are a family of antioxidant enzymes involved in a myriad of cellular functions and diseases. During the reaction with peroxides (e.g., H(2)O(2)), the typical 2-Cys Prxs change oligomeric structure between higher order (do)decamers and disulfide-linked dimers, with the hyperoxidized inactive state (-SO(2)H) favoring the multimeric structure of the reduced enzyme. Here, we present a study on the structural requirements for the repair of hyperoxidized 2-Cys Prxs by human sulfiredoxin (Srx) and the relative efficacy of physiological reductants hydrogen sulfide (H(2)S) and glutathione (GSH) in this reaction. The crystal structure of the toroidal Prx1-Srx complex shows an extended active site interface. The loss of this interface within engineered Prx2 and Prx3 dimers yielded variants more resistant to hyperoxidation and repair by Srx. Finally, we reveal for the first time Prx isoform-dependent use of and potential cooperation between GSH and H(2)S in supporting Srx activity. |
format | Online Article Text |
id | pubmed-8230665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82306652021-06-26 Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State Forshaw, Tom E. Reisz, Julie A. Nelson, Kimberly J. Gumpena, Rajesh Lawson, J. Reed Jönsson, Thomas J. Wu, Hanzhi Clodfelter, Jill E. Johnson, Lynnette C. Furdui, Cristina M. Lowther, W. Todd Antioxidants (Basel) Article Human peroxiredoxins (Prx) are a family of antioxidant enzymes involved in a myriad of cellular functions and diseases. During the reaction with peroxides (e.g., H(2)O(2)), the typical 2-Cys Prxs change oligomeric structure between higher order (do)decamers and disulfide-linked dimers, with the hyperoxidized inactive state (-SO(2)H) favoring the multimeric structure of the reduced enzyme. Here, we present a study on the structural requirements for the repair of hyperoxidized 2-Cys Prxs by human sulfiredoxin (Srx) and the relative efficacy of physiological reductants hydrogen sulfide (H(2)S) and glutathione (GSH) in this reaction. The crystal structure of the toroidal Prx1-Srx complex shows an extended active site interface. The loss of this interface within engineered Prx2 and Prx3 dimers yielded variants more resistant to hyperoxidation and repair by Srx. Finally, we reveal for the first time Prx isoform-dependent use of and potential cooperation between GSH and H(2)S in supporting Srx activity. MDPI 2021-06-11 /pmc/articles/PMC8230665/ /pubmed/34208049 http://dx.doi.org/10.3390/antiox10060946 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Forshaw, Tom E. Reisz, Julie A. Nelson, Kimberly J. Gumpena, Rajesh Lawson, J. Reed Jönsson, Thomas J. Wu, Hanzhi Clodfelter, Jill E. Johnson, Lynnette C. Furdui, Cristina M. Lowther, W. Todd Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State |
title | Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State |
title_full | Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State |
title_fullStr | Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State |
title_full_unstemmed | Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State |
title_short | Specificity of Human Sulfiredoxin for Reductant and Peroxiredoxin Oligomeric State |
title_sort | specificity of human sulfiredoxin for reductant and peroxiredoxin oligomeric state |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230665/ https://www.ncbi.nlm.nih.gov/pubmed/34208049 http://dx.doi.org/10.3390/antiox10060946 |
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