Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation

<i>Fusobacterium nucleatum</i> is one of the most notorious species involved in colorectal cancer. It was reported that numerous outer membrane proteins (OMP) are actively involved in carcinogenesis. In this paper, the structure and stability of certain complexes, as well as DNA cleavage...

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Autores principales:	Kamila Stokowa-Sołtys, Kamil Wojtkowiak, Valentyn Dzyhovskyi, Robert Wieczorek
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	porin protein P1 <i>Fusobacterium nucleatum</i> copper(II) binding DNA degradation reactive oxygen species generation NDMA decomposition Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/b1ea413aa5ff42818f84832cac53edf3
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spelling	oai:doaj.org-article:b1ea413aa5ff42818f84832cac53edf32021-11-25T17:57:39ZEffect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation10.3390/ijms2222125411422-00671661-6596https://doaj.org/article/b1ea413aa5ff42818f84832cac53edf32021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12541https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>Fusobacterium nucleatum</i> is one of the most notorious species involved in colorectal cancer. It was reported that numerous outer membrane proteins (OMP) are actively involved in carcinogenesis. In this paper, the structure and stability of certain complexes, as well as DNA cleavage and ROS generation by fragments of OMP, were investigated using experimental and theoretical methods. Mass spectrometry, potentiometry, UV-Vis, CD, EPR, gel electrophoresis and calculations at the density functional theory (DFT) level were applied. Two consecutive model peptides, Ac-AKGHEHQLE-NH<sub>2</sub> and Ac-FGEHEHGRD-NH<sub>2</sub>, were studied. Both of these were rendered to form a variety of thermodynamically stable complexes with copper(II) ions. All of the complexes were stabilized, mainly due to interactions of metal with nitrogen and oxygen donor atoms, as well as rich hydrogen bond networks. It was also concluded that these complexes in the presence of hydrogen peroxide or ascorbic acid can effectively produce hydroxyl radicals and have an ability to cleave the DNA strands. Surprisingly, the second studied ligand at the micromolar concentration range causes overall DNA degradation.Kamila Stokowa-SołtysKamil WojtkowiakValentyn DzyhovskyiRobert WieczorekMDPI AGarticleporin protein P1<i>Fusobacterium nucleatum</i>copper(II) bindingDNA degradationreactive oxygen species generationNDMA decompositionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12541, p 12541 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	porin protein P1 <i>Fusobacterium nucleatum</i> copper(II) binding DNA degradation reactive oxygen species generation NDMA decomposition Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	porin protein P1 <i>Fusobacterium nucleatum</i> copper(II) binding DNA degradation reactive oxygen species generation NDMA decomposition Biology (General) QH301-705.5 Chemistry QD1-999 Kamila Stokowa-Sołtys Kamil Wojtkowiak Valentyn Dzyhovskyi Robert Wieczorek Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation
description	<i>Fusobacterium nucleatum</i> is one of the most notorious species involved in colorectal cancer. It was reported that numerous outer membrane proteins (OMP) are actively involved in carcinogenesis. In this paper, the structure and stability of certain complexes, as well as DNA cleavage and ROS generation by fragments of OMP, were investigated using experimental and theoretical methods. Mass spectrometry, potentiometry, UV-Vis, CD, EPR, gel electrophoresis and calculations at the density functional theory (DFT) level were applied. Two consecutive model peptides, Ac-AKGHEHQLE-NH<sub>2</sub> and Ac-FGEHEHGRD-NH<sub>2</sub>, were studied. Both of these were rendered to form a variety of thermodynamically stable complexes with copper(II) ions. All of the complexes were stabilized, mainly due to interactions of metal with nitrogen and oxygen donor atoms, as well as rich hydrogen bond networks. It was also concluded that these complexes in the presence of hydrogen peroxide or ascorbic acid can effectively produce hydroxyl radicals and have an ability to cleave the DNA strands. Surprisingly, the second studied ligand at the micromolar concentration range causes overall DNA degradation.
format	article
author	Kamila Stokowa-Sołtys Kamil Wojtkowiak Valentyn Dzyhovskyi Robert Wieczorek
author_facet	Kamila Stokowa-Sołtys Kamil Wojtkowiak Valentyn Dzyhovskyi Robert Wieczorek
author_sort	Kamila Stokowa-Sołtys
title	Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation
title_short	Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation
title_full	Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation
title_fullStr	Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation
title_full_unstemmed	Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation
title_sort	effect of copper(ii) ion binding by porin p1 precursor fragments from <i>fusobacterium nucleatum</i> on dna degradation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b1ea413aa5ff42818f84832cac53edf3
work_keys_str_mv	AT kamilastokowasołtys effectofcopperiiionbindingbyporinp1precursorfragmentsfromifusobacteriumnucleatumiondnadegradation AT kamilwojtkowiak effectofcopperiiionbindingbyporinp1precursorfragmentsfromifusobacteriumnucleatumiondnadegradation AT valentyndzyhovskyi effectofcopperiiionbindingbyporinp1precursorfragmentsfromifusobacteriumnucleatumiondnadegradation AT robertwieczorek effectofcopperiiionbindingbyporinp1precursorfragmentsfromifusobacteriumnucleatumiondnadegradation
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Effect of Copper(II) Ion Binding by Porin P1 Precursor Fragments from <i>Fusobacterium nucleatum</i> on DNA Degradation

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