Ni(II) carcinogenesis and binding to Cap43 protein

Nickel compunds are well known as human carcinogens. The carcinogenity of nickel compounds has been confirmed by numerous epidemiological studies in humans and animals. The leading concepts in nickel carcinogenesis involves oxidative promutagenic DNA damage and epigenetic effects in chromatin resulting from nickel binding inside the cell nucleus. We have analyzed, for Ni(II) binding, the 30-amino acid C-terminal fragment of the protein, by a combined pH-metric and spectroscopic study. The fragment showed to bind one, two and three metal ions depending on the metal to ligand molar ratio

Nickel binding to Cap43 protein

Cap43 has been reported to be specifically induced by nickel compounds in a variety of cell lines. Although the function of Cap43 protein (MW 43,000) is not clear, it does appear to be induced in response to an increase in intracellular concentration of Ca2+, caused by nickel ion exposure in cultured human cells, for this reason is named Cap43: Calcium protein 43,000. Cap43 protein is expressed at low levels in normal tissues however, it is overexpressed in cancer cells. The high level of expression in cancerous status combined with the elevated stability of Cap43 protein makes it an excellent cancer marker. A possible way to better understand the molecular mechanisms implicated in toxicity and carcinogenicity of nickel compounds is to study the characteristics of the proteins expressed by the genes specifically induced by these carcinogens. For this reason we focused our attention to investigate the interaction ability of nickel to Cap43 protein. The peculiarity of Cap43 protein is in its new mono-histidinic motif consisting of ten amino acids TRSRSHTSEG fragment repeated three times in the C-terminus.</br

Nickel interaction with metal binding sequences of histone H4

Nickel compounds are well known as human carcinogens. We investigated the issue of Ni(II) binding within the histone octamer. Using histone sequences in conjuction with the structural data we identified a binding site for Ni(II) ions located in the N-terminal tail of the histone H4

Cap43 protein: an attractive motif for Ni(II) in the C-terminal domain

The carcinogenicity of nickel compounds has been confirmed by numerous epidemiological studies in humans and animals. A possible way to better understand the molecular mechanisms implicated in toxicity and carcinogenicity of nickel compounds is to study the characteristics of the proteins expressed by the genes specifically induced by these carcinogens. The present work supports the existence of an interesting binding site for Ni(II) at the C-terminal domain of Cap43 protein

Copper(II) and oxovanadium(IV) complexes of alpha-hydroxymethylserine

Potentiometric and spectroscopic measurements were used to characterize the binding ability of -hydroxy-methylserine (Hms) with copper(II) and oxovanadium(IV) ions. The ligand was found to be generally a more efficient chelating agent than serine. Both of the deprotonated hydroxyl groups of Hms can be involved in coordination to vanadyl ions, whereas copper(II) binds in the same way as with serine

Copper(II) binding to Cap43 protein fragments

The C-terminal 20 and 30 amino acid sequences of Cap43 protein were chosen as models to study their interactions with Cu(II) ions. The behaviour of the 20 amino acid Ac–TRSRSH6TSEG–TRSRSH16TSEG and 30 amino acid Ac–TRSRSH6TSEG–TRSRSH16TSEG–TRSRSH26TSEG peptides towards Cu(II) ions at different pH values and different ligand-to-metal molar ratios, was examined. Spectroscopic (EPR, UV-Vis) and potentiometric techniques were performed to understand the details of metal binding to the peptides. The study showed that, starting from pH 4.0, each 10 amino acid fragment T1R2S3R4S5H6T7S8E9G10 was able to independently coordinate a single Cu(II) ion. The coordination mode involved the imidazole nitrogen of histidine H6 residue, and three amidic nitrogens from histidine H6, serine S5, and arginine R4 residues, respectively

Copper(II) complexes of dipeptides containing aspartyl, glutamyl, and histidyl residues in the side chain

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Nickel(II) binding to Cap43 protein fragments

Cap43 protein has been tested for metal binding domains. The protein, specifically induced by nickel compounds in cultured human cells, had a new mono-histidinic motif consisting of 10 amino acids repeated three times in the C-terminus. The 20-Ac-TRSRSHTSEG–TRSRSHTSEG (Thr341–Arg–Ser–Arg–Ser–His 346–Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His356 –Thr–Ser–Glu–Gly360 – peptide 1) and the 30–Ac-TRSRSHTSEG–TRSRSHTSEG–TRSRSHTSEG (Thr341 –Arg–Ser–Arg–Ser–His346 –Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His356 –Thr–Ser–Glu–Gly–Thr–Arg–Ser–Arg–Ser–His366 –Thr–Ser–Glu–Gly 370 – peptide 2) amino acids sequence has been analyzed as a site for Ni(II) binding. A combined pH-metric and spectroscopic (UV–visible, CD, NMR) studies of Ni(II) binding to both fragments were performed. The 20-amino acid peptide can bind one and two metal ions while the 30-amino acid fragment one, two and three metal ions. At physiological pH, depending on the metal to ligand molar ratio, peptide 1 forms the Ni 2L species while peptide 2 the NiL, Ni2L and Ni3 L complexes where each metal ion is coordinated to the imidazole nitrogen atom of the histidine residue of the 10-amino acid fragment. Octahedral complexes at pH 8–9 and planar 4N complexes with (N Im , 3N − ) bonding mode at pH above 9, are formed. This work supports the existence of an interesting binding site at the COOH-terminal domain of the Cap43 protein