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Article

The Reactions of H2O2 and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, But No Synergy with Cadmium Toxicity

1
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland
2
Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02097 Warsaw, Poland
3
Institute of Applied Biosciences, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Joanna Bojarska, Wojciech M. Wolf, Milan Remko, Piotr Zielenkiewicz, Michele Saviano, Janusz Zabrocki, Krzysztof Kaczmarek and Diego Muñoz-Torrero
Molecules 2020, 25(18), 4177; https://doi.org/10.3390/molecules25184177
Received: 20 August 2020 / Revised: 4 September 2020 / Accepted: 10 September 2020 / Published: 12 September 2020
(This article belongs to the Special Issue Advances in Research of Short Peptides)
Tetrathiolate zinc fingers are potential targets of oxidative assault under cellular stress conditions. We used the synthetic 37-residue peptide representing the tetrathiolate zinc finger domain of the DNA repair protein XPA, acetyl-DYVICEECGKEFMSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) as a working model to study the reaction of its Zn(II) complex (ZnXPAzf) with hydrogen peroxide and S-nitrosoglutathione (GSNO), as oxidative and nitrosative stress agents, respectively. We also used the Cd(II) substituted XPAzf (CdXPAzf) to assess the situation of cadmium assault, which is accompanied by oxidative stress. Using electrospray mass spectrometry (ESI-MS), HPLC, and UV-vis and circular dichroism spectroscopies we demonstrated that even very low levels of H2O2 and GSNO invariably cause irreversible thiol oxidation and concomitant Zn(II) release from ZnXPAzf. In contrast, CdXPAzf was more resistant to oxidation, demonstrating the absence of synergy between cadmium and oxidative stresses. Our results indicate that GSNO cannot act as a reversible modifier of XPA, and rather has a deleterious effect on DNA repair. View Full-Text
Keywords: zinc fingers; zinc; cadmium; hydrogen peroxide; S-nitrosoglutathione; oxidation zinc fingers; zinc; cadmium; hydrogen peroxide; S-nitrosoglutathione; oxidation
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MDPI and ACS Style

Witkiewicz-Kucharczyk, A.; Goch, W.; Olędzki, J.; Hartwig, A.; Bal, W. The Reactions of H2O2 and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, But No Synergy with Cadmium Toxicity. Molecules 2020, 25, 4177. https://doi.org/10.3390/molecules25184177

AMA Style

Witkiewicz-Kucharczyk A, Goch W, Olędzki J, Hartwig A, Bal W. The Reactions of H2O2 and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, But No Synergy with Cadmium Toxicity. Molecules. 2020; 25(18):4177. https://doi.org/10.3390/molecules25184177

Chicago/Turabian Style

Witkiewicz-Kucharczyk, Aleksandra, Wojciech Goch, Jacek Olędzki, Andrea Hartwig, and Wojciech Bal. 2020. "The Reactions of H2O2 and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, But No Synergy with Cadmium Toxicity" Molecules 25, no. 18: 4177. https://doi.org/10.3390/molecules25184177

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