Publication
Title
The effect of reactive oxygen and nitrogen species on the structure of cytoglobin: a potential tumor suppressor
Author
Abstract
Many current anti-cancer therapies rely on increasing the intracellular reactive oxygen and nitrogen species (RONS) contents with the aim to induce irreparable damage, which subsequently results in tumor cell death. A novel tool in cancer therapy is the use of cold atmospheric plasma (CAP), which has been found to be very effective in the treatment of many different cancer cell types in vitro as well as in vivo, mainly through the vast generation of RONS. One of the key determinants of the cell's fate will be the interaction of RONS, generated by CAP, with important proteins, i.e. redox-regulatory proteins. One such protein is cytoglobin (CYGB), a recently discovered globin proposed to be involved in the protection of the cell against oxidative stress. In this study, the effect of plasma-produced RONS on CYGB was investigated through the treatment of CYGB with CAP for different treatment times. Spectroscopic analysis of CYGB showed that although chemical modifications occur, its secondary structure remains intact. Mass spectrometry experiments identified these modifications as oxidations of mainly sulfur-containing and aromatic amino acids. With longer treatment time, the treatment was also found to induce nitration of the heme. Furthermore, the two surface-exposed cysteine residues of CYGB were oxidized upon treatment, leading to the formation of intermolecular disulfide bridges, and potentially also intramolecular disulfide bridges. In addition, molecular dynamics and docking simulations confirmed, and further show, that the formation of an intramolecular disulfide bond, due to oxidative conditions, affects the CYGB 3D structure, thereby opening the access to the heme group, through gate functioning of His117. Altogether, the results obtained in this study (1) show that plasma-produced RONS can extensively oxidize proteins and (2) that the oxidation status of two redox-active cysteines lead to different conformations of CYGB.
Language
English
Source (journal)
Redox Biology
Redox Biology
Publication
2018
ISSN
2213-2317
Volume/pages
19 (2018) , p. 1-10
ISI
000449722100002
Pubmed ID
30081385
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Atomic scale modeling for plasma cancer treatment.
Towards a fundamental understanding of plasma for cancer treatment: A combined experimental and computational study.
Unravelling structural motives of intrinsically unstructured proteins employing Raman optical activity: Understanding the basis of neurodegenerative diseases
Targeted immobilization of globin proteins on porous materials for electrochemical applications.
4D Protein Structure.
Towards new approaches in bioelectrochemistry – Targeted immobilization of globins on porous materials.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 20.08.2018
Last edited 20.09.2021
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