The extraordinary catalytic ability of peroxiredoxins: a combined experimental and QM/MM study on the fast thiol oxidation step
Year: 2014
Type: article
Abstract: 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 10(3)-10(7) 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.
Source: Chemical Communications
DOI: 10.1039/c4cc02899f
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Agencia Nacional de Investigación e Innovación, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Universidad de la República Uruguay, National Institutes of Health, Health Services and Delivery Research Programme, Comisión Sectorial de Investigación Científica, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W2097352427