Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability

Abstract Recently it was proposed that the redox status of cysteines acts as a redox switch to regulate both the oligomeric status and the activity of human dUTPase. In a separate report, a human dUTPase point mutation, resulting in a tyrosine to cysteine substitution (Y54C) was identified as the mo...

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Autores principales:	Judit Eszter Szabó, Kinga Nyíri, Dániel Andrási, Judit Matejka, Olivér Ozahonics, Beáta Vértessy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2ca105caedc490383b7eed748bef8b8
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spelling	oai:doaj.org-article:e2ca105caedc490383b7eed748bef8b82021-12-02T17:18:22ZRedox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability10.1038/s41598-021-98790-32045-2322https://doaj.org/article/e2ca105caedc490383b7eed748bef8b82021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98790-3https://doaj.org/toc/2045-2322Abstract Recently it was proposed that the redox status of cysteines acts as a redox switch to regulate both the oligomeric status and the activity of human dUTPase. In a separate report, a human dUTPase point mutation, resulting in a tyrosine to cysteine substitution (Y54C) was identified as the monogenic cause of a rare syndrome associated with diabetes and bone marrow failure. These issues prompt a critical investigation about the potential regulatory role of cysteines in the enzyme. Here we show on the one hand that independently of the redox status of wild-type cysteines, human dUTPase retains its characteristic trimeric assembly and its catalytic activity. On the other hand, the Y54C mutation did not compromise the substrate binding and the catalytic properties of the enzyme at room temperature. The thermal stability of the mutant protein was found to be decreased, which resulted in the loss of 67% of its activity after 90 min incubation at the physiological temperature in contrast to the wild-type enzyme. In addition, the presence or absence of reducing agents had no effect on hDUTY54C activity and stability, although it was confirmed that the introduced cysteine contains a solvent accessible thiol group.Judit Eszter SzabóKinga NyíriDániel AndrásiJudit MatejkaOlivér OzahonicsBeáta VértessyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Judit Eszter Szabó Kinga Nyíri Dániel Andrási Judit Matejka Olivér Ozahonics Beáta Vértessy Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability
description	Abstract Recently it was proposed that the redox status of cysteines acts as a redox switch to regulate both the oligomeric status and the activity of human dUTPase. In a separate report, a human dUTPase point mutation, resulting in a tyrosine to cysteine substitution (Y54C) was identified as the monogenic cause of a rare syndrome associated with diabetes and bone marrow failure. These issues prompt a critical investigation about the potential regulatory role of cysteines in the enzyme. Here we show on the one hand that independently of the redox status of wild-type cysteines, human dUTPase retains its characteristic trimeric assembly and its catalytic activity. On the other hand, the Y54C mutation did not compromise the substrate binding and the catalytic properties of the enzyme at room temperature. The thermal stability of the mutant protein was found to be decreased, which resulted in the loss of 67% of its activity after 90 min incubation at the physiological temperature in contrast to the wild-type enzyme. In addition, the presence or absence of reducing agents had no effect on hDUTY54C activity and stability, although it was confirmed that the introduced cysteine contains a solvent accessible thiol group.
format	article
author	Judit Eszter Szabó Kinga Nyíri Dániel Andrási Judit Matejka Olivér Ozahonics Beáta Vértessy
author_facet	Judit Eszter Szabó Kinga Nyíri Dániel Andrási Judit Matejka Olivér Ozahonics Beáta Vértessy
author_sort	Judit Eszter Szabó
title	Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability
title_short	Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability
title_full	Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability
title_fullStr	Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability
title_full_unstemmed	Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability
title_sort	redox status of cysteines does not alter functional properties of human dutpase but the y54c mutation involved in monogenic diabetes decreases protein stability
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e2ca105caedc490383b7eed748bef8b8
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Redox status of cysteines does not alter functional properties of human dUTPase but the Y54C mutation involved in monogenic diabetes decreases protein stability

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