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

• Published in: International journal of molecular sciences 2021-11, Vol.22 (22), p.12541
• Main Authors: Stokowa-Sołtys, Kamila, Wojtkowiak, Kamil, Dzyhovskyi, Valentyn, Wieczorek, Robert
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence - genetics; Ascorbic acid; Bacteria; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - drug effects; Bacterial Outer Membrane Proteins - genetics; Cadmium; Cancer; Carcinogenesis; Carcinogens; Colorectal carcinoma; Competition; Copper - chemistry; Copper - pharmacology; copper(II) binding; Density functional theory; Deoxyribonucleic acid; DNA; DNA - genetics; DNA Cleavage - drug effects; DNA damage; DNA degradation; DNA Fragmentation - drug effects; Electrical measurement; Electrophoresis; Fragments; Free radicals; Fusobacterium nucleatum; Fusobacterium nucleatum - genetics; Gel electrophoresis; Hydrogen bonds; Hydrogen peroxide; Hydrogen Peroxide - chemistry; Hydroxyl radicals; Ions - chemistry; Ions - pharmacology; Ligands; Mass Spectrometry; Mass spectroscopy; Membrane proteins; Microbiota; NDMA decomposition; Outer membrane proteins; Oxidative stress; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptides; porin protein P1; Porins - genetics; Potentiometric analysis; Potentiometry; Proteins; Reactive Oxygen Species - metabolism; reactive oxygen species generation; Scientific imaging; Structural stability
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222212541

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 and Ac-FGEHEHGRD-NH , 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.