Mechanistic insights into the urea-induced denaturation of a non-seleno thiol specific antioxidant human peroxiredoxin 6.
In: International journal of biological macromolecules, Jg. 161 (2020-10-15), S. 1171-1180
academicJournal
Zugriff:
Peroxiredoxin 6 (Prdx6) is a unique enzyme among mammalian peroxiredoxins as it lacks resolving cysteine. It is found to be involved in number of different diseases including tumours and its expression level is highest in lungs as compared to other organs. It has been found that Prdx6 plays a significant role different metabolic diseases, ocular damage, neurodegeneration and male infertility. It is a bifunctional protein having phospholipase A 2 and peroxidase (also has the ability to reduce phospholipid hydroperoxides) activities. In order to complete the peroxidise reaction cycle it requires glutathione catalyzed by glutathione S-transferase. Equilibrium unfolding and conformational stability of Prdx6 was studied by using urea as a chemical denaturant to understand the changes it goes under cellular stress conditions. Three different spectroscopic methods were employed to monitor urea-induced denaturation. From the results obtained, it was found that the urea denaturation of Prdx6 follows a variable two state process due to non-coincidence of the normalized transition curves obtained from different optical probes. The different denaturation curves were normalized and thermodynamic parameters, ΔG D o , Gibbs free energy change related to the urea-induced denaturation, midpoint of denaturation (C m ), and m = (δΔG D / [urea]) were obtained. The structural information of Prdx6 were further analysed by several parameters obtained by 100 ns MD simulation. The results of MD simulation clearly favour the outcome of spectroscopic studies.
Competing Interests: Declaration of competing interest Authors declare there is no conflict of interest.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
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Mechanistic insights into the urea-induced denaturation of a non-seleno thiol specific antioxidant human peroxiredoxin 6.
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Autor/in / Beteiligte Person: | Qausain, S ; Khan, FI ; Lai, D ; Hassan, MI ; Basheeruddin, M ; Ahmed, N ; Khan, MKA |
Zeitschrift: | International journal of biological macromolecules, Jg. 161 (2020-10-15), S. 1171-1180 |
Veröffentlichung: | Amsterdam : Elsevier ; <i>Original Publication</i>: Guildford, Eng., IPC Science and Technology Press., 2020 |
Medientyp: | academicJournal |
ISSN: | 1879-0003 (electronic) |
DOI: | 10.1016/j.ijbiomac.2020.05.168 |
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