Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase
The activity of the erythrocyte Cu(2),Zn(2)-superoxide dismutase (SOD1) is altered in Alzheimer's disease (AD) patients. These patients, compared to healthy subjects, exhibit low plasmatic zinc (Zn) levels in the presence of high plasmatic levels of copper (Cu). SOD1 is an antioxidant enzyme ch...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848637/ https://www.ncbi.nlm.nih.gov/pubmed/33553758 http://dx.doi.org/10.1016/j.heliyon.2021.e06100 |
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author | Manieri, Tania M. Sensi, Stefano L. Squitti, Rosanna Cerchiaro, Giselle |
author_facet | Manieri, Tania M. Sensi, Stefano L. Squitti, Rosanna Cerchiaro, Giselle |
author_sort | Manieri, Tania M. |
collection | PubMed |
description | The activity of the erythrocyte Cu(2),Zn(2)-superoxide dismutase (SOD1) is altered in Alzheimer's disease (AD) patients. These patients, compared to healthy subjects, exhibit low plasmatic zinc (Zn) levels in the presence of high plasmatic levels of copper (Cu). SOD1 is an antioxidant enzyme characterized by the presence of two metal ions, Cu and Zn, on its active site. On the SOD1, Cu exerts a catalytic role, and Zn serves a structural function. In this study, we generated a modified SOD1 characterized by an altered capacity to complex Zn. The study investigates the metal-binding dynamics of the enzyme, estimating the stability of a SOD1 protein lacking the appropriate Zn site complexation. Our mutant SOD1 possesses a double amino acid mutation (T135S and K136E) that interferes with the correct Zn site complexation. We found that the protein mutations produce unstable Zn coordination and lower enzymatic activity even when complexed with Cu. Analysis with circular dichroism (CD) spectra on metal titration showed a considerable difference between the two Zn entries in the native dimeric enzyme, and Cu presents a simultaneous entrance in the protein. Otherwise, the mutant T135S,K136E-SOD1 exhibited Zn and Cu complexation instability, being a useful in vitro model to study the SOD1 behavior in AD patients. |
format | Online Article Text |
id | pubmed-7848637 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-78486372021-02-04 Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase Manieri, Tania M. Sensi, Stefano L. Squitti, Rosanna Cerchiaro, Giselle Heliyon Research Article The activity of the erythrocyte Cu(2),Zn(2)-superoxide dismutase (SOD1) is altered in Alzheimer's disease (AD) patients. These patients, compared to healthy subjects, exhibit low plasmatic zinc (Zn) levels in the presence of high plasmatic levels of copper (Cu). SOD1 is an antioxidant enzyme characterized by the presence of two metal ions, Cu and Zn, on its active site. On the SOD1, Cu exerts a catalytic role, and Zn serves a structural function. In this study, we generated a modified SOD1 characterized by an altered capacity to complex Zn. The study investigates the metal-binding dynamics of the enzyme, estimating the stability of a SOD1 protein lacking the appropriate Zn site complexation. Our mutant SOD1 possesses a double amino acid mutation (T135S and K136E) that interferes with the correct Zn site complexation. We found that the protein mutations produce unstable Zn coordination and lower enzymatic activity even when complexed with Cu. Analysis with circular dichroism (CD) spectra on metal titration showed a considerable difference between the two Zn entries in the native dimeric enzyme, and Cu presents a simultaneous entrance in the protein. Otherwise, the mutant T135S,K136E-SOD1 exhibited Zn and Cu complexation instability, being a useful in vitro model to study the SOD1 behavior in AD patients. Elsevier 2021-01-28 /pmc/articles/PMC7848637/ /pubmed/33553758 http://dx.doi.org/10.1016/j.heliyon.2021.e06100 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Manieri, Tania M. Sensi, Stefano L. Squitti, Rosanna Cerchiaro, Giselle Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase |
title | Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase |
title_full | Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase |
title_fullStr | Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase |
title_full_unstemmed | Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase |
title_short | Structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase |
title_sort | structural effects of stabilization and complexation of a zinc-deficient superoxide dismutase |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848637/ https://www.ncbi.nlm.nih.gov/pubmed/33553758 http://dx.doi.org/10.1016/j.heliyon.2021.e06100 |
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