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Reaction of the XPA zinc finger with S-nitrosoglutathione.
Chem Res Toxicol. 2008 Feb; 21(2):386-92.CR

Abstract

S-Nitrosoglutathione (GSNO) is an intracellular redox signaling molecule, also implicated in nitrosative stress. GSNO actions include modifications of Cys thiols in proteins. In this study, we focused on a GSNO reaction with a Cys4 zinc finger (ZF) sequence of human protein XPA, crucial to the nucleotide excision repair pathway of DNA repair. By using a corresponding synthetic 37-residue peptide acetyl-DYVICEECGKEFMDSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) and combining the detection of noncovalent and covalent complexes by ESI-MS with zinc release monitored by the zinc-sensitive chromophore 4-(2-pyridylazo)resorcinol (PAR), we demonstrated that the reaction of XPAzf with GSNO yielded S-nitrosylated intermediates, intrapeptide disulfides, and mixed glutathione disulfides. The reaction started with the formation of a complex of GSNO with ZnXPAzf followed by thiol transnitrosylation reactions and the final formation of disulfides. The results obtained suggest that at low levels/transient exposures, GSNO may act as a reversible regulator of Cys4 ZF activity, whereas transnitrosylation by GSNO, occurring at prolonged exposures, may cause deleterious effects to the functions of Cys 4 ZF proteins. In the case of XPA, this may lead to DNA repair inhibition.

Authors+Show Affiliations

Department of Gene Technology, Tallinn Technical University, Akadeemia tee 15, 12618 Tallinn, Estonia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18171019

Citation

Smirnova, Julia, et al. "Reaction of the XPA Zinc Finger With S-nitrosoglutathione." Chemical Research in Toxicology, vol. 21, no. 2, 2008, pp. 386-92.
Smirnova J, Zhukova L, Witkiewicz-Kucharczyk A, et al. Reaction of the XPA zinc finger with S-nitrosoglutathione. Chem Res Toxicol. 2008;21(2):386-92.
Smirnova, J., Zhukova, L., Witkiewicz-Kucharczyk, A., Kopera, E., Oledzki, J., Wysłouch-Cieszyńska, A., Palumaa, P., Hartwig, A., & Bal, W. (2008). Reaction of the XPA zinc finger with S-nitrosoglutathione. Chemical Research in Toxicology, 21(2), 386-92. https://doi.org/10.1021/tx700297f
Smirnova J, et al. Reaction of the XPA Zinc Finger With S-nitrosoglutathione. Chem Res Toxicol. 2008;21(2):386-92. PubMed PMID: 18171019.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reaction of the XPA zinc finger with S-nitrosoglutathione. AU - Smirnova,Julia, AU - Zhukova,Liliya, AU - Witkiewicz-Kucharczyk,Aleksandra, AU - Kopera,Edyta, AU - Oledzki,Jacek, AU - Wysłouch-Cieszyńska,Aleksandra, AU - Palumaa,Peep, AU - Hartwig,Andrea, AU - Bal,Wojciech, Y1 - 2008/01/03/ PY - 2008/1/4/pubmed PY - 2008/4/9/medline PY - 2008/1/4/entrez SP - 386 EP - 92 JF - Chemical research in toxicology JO - Chem Res Toxicol VL - 21 IS - 2 N2 - S-Nitrosoglutathione (GSNO) is an intracellular redox signaling molecule, also implicated in nitrosative stress. GSNO actions include modifications of Cys thiols in proteins. In this study, we focused on a GSNO reaction with a Cys4 zinc finger (ZF) sequence of human protein XPA, crucial to the nucleotide excision repair pathway of DNA repair. By using a corresponding synthetic 37-residue peptide acetyl-DYVICEECGKEFMDSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) and combining the detection of noncovalent and covalent complexes by ESI-MS with zinc release monitored by the zinc-sensitive chromophore 4-(2-pyridylazo)resorcinol (PAR), we demonstrated that the reaction of XPAzf with GSNO yielded S-nitrosylated intermediates, intrapeptide disulfides, and mixed glutathione disulfides. The reaction started with the formation of a complex of GSNO with ZnXPAzf followed by thiol transnitrosylation reactions and the final formation of disulfides. The results obtained suggest that at low levels/transient exposures, GSNO may act as a reversible regulator of Cys4 ZF activity, whereas transnitrosylation by GSNO, occurring at prolonged exposures, may cause deleterious effects to the functions of Cys 4 ZF proteins. In the case of XPA, this may lead to DNA repair inhibition. SN - 0893-228X UR - https://www.unboundmedicine.com/medline/citation/18171019/Reaction_of_the_XPA_zinc_finger_with_S_nitrosoglutathione_ L2 - https://doi.org/10.1021/tx700297f DB - PRIME DP - Unbound Medicine ER -