Copper effective binding with 32–62 and 94–125 peptide fragments of histone H2B

Amino acid-based tweezers: The role of turn-like conformation in the binding of copper(II)

“…Again, stabilities of complexes with 2, 3 and 4 nitrogen atoms coordinated to the Cu(II) ion (log K ⁎ ≈8, 15 and 24 respectively) are similar to those obtained in our work, with the most expressed discrepancy in the case of human Aβ peptide fragment showing additional stabilization of the complexes. As stated earlier, significantly lower stability of the LH −3 Cu − species compared to other 4N complexes [22,23] is a consequence of unfavorable H 2 O deprotonation, whereas the increase in log K ⁎ of the LH −2 Cu (3a) is caused by a cooperative amide deprotonation.…”

“…Since the log K ⁎ values for the compounds investigated in our work are in the same range (−8.06 to −6.65), it can be concluded that the lack of His residual in the ligand structure can be overcome by its rigidity and cooperative binding by two amine groups. Even in the case of more complex peptides, like histone H2B fragments [22] or human and mouse Aβ peptide fragments [23] containing His moieties, stability of the Cu(II) complex can be correlated to those of the ligands 3. Again, stabilities of complexes with 2, 3 and 4 nitrogen atoms coordinated to the Cu(II) ion (log K ⁎ ≈8, 15 and 24 respectively) are similar to those obtained in our work, with the most expressed discrepancy in the case of human Aβ peptide fragment showing additional stabilization of the complexes.…”

Influence of Toxicologically Relevant Metals on Human Epigenetic Regulation

“…Cu can directly bind to with critical histidine residues of histones H2A, H3 and H4 in vitro (50 , 51) . Cu binding to the C-terminal peptide of H2B (H2B94-125) could interfere with the ubiquitination of Lys120, which has been associated with gene silencing (52 , 53) . In addition to histones, Cu interacts with DNA, resulting in induced conformational changes of chromatin and altered gene expression.…”

Mechanisms of Base Substitution Mutagenesis in Cancer Genomes

“…The number of single base lesions was found to be 8-fold higher on nucleosomal DNA than on isolated DNA, implying that Fenton chemistry is not only unrestricted by chromatin compaction but actually appears to be facilitated [111]. Although the roles of histone octamers in permitting DNA damage are not fully understood, X-ray crystal structure studies revealed the presence of many divalent metal binding sites in nucleosome particles [112], and several peptide models of histones H2A, H2B, H3 and H4 have been shown to coordinate Cu(II), mostly through macrochelate rings involving histidine and carboxylate groups [113]. The extremely short (<1 ns) half-life of OH likely restricts Fenton chemistry at sites of OH generation.…”