The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step
Peroxiredoxins (Prxs) catalyze the reduction of peroxides, a process of key relevance in a variety of cellular processes. The first step in the catalytic cycle of all Prxs is the oxidation of a cysteine residue to sulfenic acid, which occurs 103-107 times faster than in free cysteine. We present an...
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2014
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13597345_v50_n70_p10070_Zeida http://hdl.handle.net/20.500.12110/paper_13597345_v50_n70_p10070_Zeida |
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paper:paper_13597345_v50_n70_p10070_Zeida2023-06-08T16:11:29Z The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step hydrogen peroxide peroxiredoxin thiol peroxiredoxin thiol derivative article enthalpy entropy hybrid hydrogen bond kinetics molecular mechanics Mycobacterium tuberculosis oxidation quantum mechanics reduction simulation catalysis chemistry metabolism oxidation reduction reaction protein secondary structure quantum theory Catalysis Hydrogen Peroxide Oxidation-Reduction Peroxiredoxins Protein Structure, Secondary Quantum Theory Sulfhydryl Compounds Peroxiredoxins (Prxs) catalyze the reduction of peroxides, a process of key relevance in a variety of cellular processes. The first step in the catalytic cycle of all Prxs is the oxidation of a cysteine residue to sulfenic acid, which occurs 103-107 times faster than in free cysteine. We present an experimental kinetics and hybrid QM/MM investigation to explore the reaction of Prxs with H2O2 using alkyl hydroperoxide reductase E from Mycobacterium tuberculosis as a Prx model. We report for the first time the thermodynamic activation parameters of H2O2 reduction using Prx, which show that protein significantly lowers the activation enthalpy, with an unfavourable entropic effect, compared to the uncatalyzed reaction. The QM/MM simulations show that the remarkable catalytic effects responsible for the fast H2O2 reduction in Prxs are mainly due to an active-site arrangement, which establishes a complex hydrogen bond network activating both reactive species. This journal is © the Partner Organisations 2014. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13597345_v50_n70_p10070_Zeida http://hdl.handle.net/20.500.12110/paper_13597345_v50_n70_p10070_Zeida |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
hydrogen peroxide peroxiredoxin thiol peroxiredoxin thiol derivative article enthalpy entropy hybrid hydrogen bond kinetics molecular mechanics Mycobacterium tuberculosis oxidation quantum mechanics reduction simulation catalysis chemistry metabolism oxidation reduction reaction protein secondary structure quantum theory Catalysis Hydrogen Peroxide Oxidation-Reduction Peroxiredoxins Protein Structure, Secondary Quantum Theory Sulfhydryl Compounds |
| spellingShingle |
hydrogen peroxide peroxiredoxin thiol peroxiredoxin thiol derivative article enthalpy entropy hybrid hydrogen bond kinetics molecular mechanics Mycobacterium tuberculosis oxidation quantum mechanics reduction simulation catalysis chemistry metabolism oxidation reduction reaction protein secondary structure quantum theory Catalysis Hydrogen Peroxide Oxidation-Reduction Peroxiredoxins Protein Structure, Secondary Quantum Theory Sulfhydryl Compounds The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step |
| topic_facet |
hydrogen peroxide peroxiredoxin thiol peroxiredoxin thiol derivative article enthalpy entropy hybrid hydrogen bond kinetics molecular mechanics Mycobacterium tuberculosis oxidation quantum mechanics reduction simulation catalysis chemistry metabolism oxidation reduction reaction protein secondary structure quantum theory Catalysis Hydrogen Peroxide Oxidation-Reduction Peroxiredoxins Protein Structure, Secondary Quantum Theory Sulfhydryl Compounds |
| description |
Peroxiredoxins (Prxs) catalyze the reduction of peroxides, a process of key relevance in a variety of cellular processes. The first step in the catalytic cycle of all Prxs is the oxidation of a cysteine residue to sulfenic acid, which occurs 103-107 times faster than in free cysteine. We present an experimental kinetics and hybrid QM/MM investigation to explore the reaction of Prxs with H2O2 using alkyl hydroperoxide reductase E from Mycobacterium tuberculosis as a Prx model. We report for the first time the thermodynamic activation parameters of H2O2 reduction using Prx, which show that protein significantly lowers the activation enthalpy, with an unfavourable entropic effect, compared to the uncatalyzed reaction. The QM/MM simulations show that the remarkable catalytic effects responsible for the fast H2O2 reduction in Prxs are mainly due to an active-site arrangement, which establishes a complex hydrogen bond network activating both reactive species. This journal is © the Partner Organisations 2014. |
| title |
The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step |
| title_short |
The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step |
| title_full |
The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step |
| title_fullStr |
The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step |
| title_full_unstemmed |
The extraordinary catalytic ability of peroxiredoxins: A combined experimental and QM/MM study on the fast thiol oxidation step |
| title_sort |
extraordinary catalytic ability of peroxiredoxins: a combined experimental and qm/mm study on the fast thiol oxidation step |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13597345_v50_n70_p10070_Zeida http://hdl.handle.net/20.500.12110/paper_13597345_v50_n70_p10070_Zeida |
| _version_ |
1768542610364825600 |