Peroxynitrite-Mediated Structural Changes in Histone H2A: Biochemical and Biophysical Analysis

Author(s): Md. Asad Khan*, Md. Faiz Akram, Khursheed Alam, Haseeb Ahsan, Moshahid A. Rizvi

Journal Name: Protein & Peptide Letters

Volume 27 , Issue 10 , 2020

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Graphical Abstract:


Background: Peroxynitrite, a nitrating and oxidizing agent, is formed by the interaction between nitric oxide and superoxide radicals. H2A histone is a basic nucleoprotein and is one of the major core histones responsible for packaging DNA. It has been shown that they are highly sensitive to oxidizing and nitrating agents.

Objective: Nitration of tyrosine residues in proteins by peroxynitrite is regarded as a marker of nitrosative damage. The dityrosine bond, an oxidative covalent cross-link between two tyrosines in protein, is increasingly identified as a marker of oxidative stress, aging and neurodegerative diseases.

Methods: Peroxinitrite-mediated nitration and dinitration in H2A histone was assessed by various biophysical techniques.

Results: The data presented in this study showed that the dityrosine content was found to be elevated in H2A histone modified with peroxynitrite. The formation of dityrosine showed a decrease in fluorescence intensity, generation of a new peak in FT-IR, increase in hydrodynamic size, and loss of secondary and tertiary structure of H2A resulting in a partially folded structure.

Conclusion: We report that H2A may undergo conformational and structural changes under nitrosative and oxidative stress from the deleterious effects of peroxynitrite.

Keywords: H2A histone, peroxynitrite, dityrosine, fluorescence, protein nitration, nitration.

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Article Details

Year: 2020
Published on: 27 April, 2020
Page: [989 - 998]
Pages: 10
DOI: 10.2174/0929866527666200427213722
Price: $65

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