Role of the Chalcogen (S, Se, Te) in the Oxidation Mechanism of the Glutathione Peroxidase Active Site
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- Marco Bortoli
- Dipartimento di Scienze Chimiche Università degli Studi di Padova Via Marzolo 1 35129 Padova Italy
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- Mauro Torsello
- Present address via Trieste 38 25121 Brescia Italy
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- F. Matthias Bickelhaupt
- Department of Theoretical Chemistry and Amsterdam Center for Multiscale Modeling (ACMM) Vrije Universiteit Amsterdam De Boelelaan 1083 1081 HV Amsterdam The Netherlands
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- Laura Orian
- Dipartimento di Scienze Chimiche Università degli Studi di Padova Via Marzolo 1 35129 Padova Italy
書誌事項
- 公開日
- 2017-09-27
- 権利情報
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1002/cphc.201700743
- 公開者
- Wiley
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>The oxidation by H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> of the human phospholipid hydroperoxide glutathione peroxidase (GPx4), used as a model peroxidase selenoenzyme, as well as that of its cysteine (Cys) and tellurocysteine (Tec) mutants, was investigated in silico through a combined classic and quantum mechanics approach to assess the role of the different chalcogens. To perform this analysis, new parameters for selenocysteine (Sec) and tellurocysteine (Tec) were accurately derived for the AMBER ff14SB force field. The oxidation represents the initial step of the antioxidant activity of GPx, which catalyzes the reduction of H<jats:sub>2</jats:sub>O<jats:sub>2</jats:sub> and organic hydroperoxides by glutathione (GSH). A mechanism involving a charge‐separation intermediate is feasible for the Cys and Sec enzymes, leading from the initial thiol/selenol form to sulfenic/selenenic acid, whereas for the Tec mutant a direct oxidation pathway is proposed. Activation strain analyses, performed for Cys‐GPx and Sec‐GPx, provided insight into the rate‐accelerating effect of selenium as compared to sulfur and the role of specific amino acids other than Cys/Sec that are typically conserved in the catalytic pocket.</jats:p>
収録刊行物
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- ChemPhysChem
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ChemPhysChem 18 (21), 2990-2998, 2017-09-27
Wiley