Coordination properties of Cu(ii) and Ni(ii) ions towards the C-terminal peptide fragment -TYTEHA- of histone H4

Abstract

In order to reveal more information about the toxicity caused by metals and furthermore their influence to the physiological metabolism of the cell, the hexapeptide model Ac-ThrTyrThrGluHisAla-am representing the C-terminal 71-76 fragment of histone H4 which lies into the nucleosome core, was synthesized. A combined pH-metric and spectroscopic UV-VIS, EPR, CD and NMR study of Ni(II) and Cu(II) binding to the blocked hexapeptide, revealed the formation of octahedral complexes involving imidazole nitrogen of histidine, at pH 5 and pH 7 for Cu(II) and Ni(II) ions respectively. In basic solutions a major square-planar 4 N Ni(II)-complex, adopting a {N(Im), 3N(-)} coordination mode, was formed. In the case of Cu(II) ions, a 3 N complex, involving the imidazole nitrogen of histidine and two deprotonated amide nitrogens of the backbone of the peptide, at pH 7 and a series of 4 N complexes starting at pH 6.5, were suggested. In addition Ni(II)-mediated hydrolysis of the peptide bond-Tyr-Thr was evident following our experimental data.

Cu(II) and Ni(II) Interactions with the Terminally Blocked Hexapeptide Ac-Leu-Ala-His-Tyr-Asn-Lys-amide Model of Histone H2B (80–85)

“…No hydrolysis of the peptide was observed upon coordination to both Ni(II) and Cu(II) metal ions, in accordance to the same proposed mechanism of our group [10, 14] and others [9, 12] for such a process, implying the presence of a Ser- or Thr-containing an –OH group near the coordination sites [10, 14] to be important for the hydrolytic process. The formation of a 4N planar Ni(II) complex reported to be an important factor as well [9] is also present in our system.…”

“…In this respect, previous studies have shown that certain histone peptide model, fragments of H2A, H2B, H3, and H4 may serve as efficient binding sites for metal ions such as Cu(II) and Ni(II) [2–14]. Moreover, interactions of metal ions with small peptides have revealed that His residues are the major coordination sites of several transition metal ions, including Ni(II) and Cu(II), in proteins [15–18].…”

“…Continuing our work, we have recently reported the efficient binding of the blocked hexapeptide -ELAKHA- model of the C-terminal of histone H2B to Cu(II) and Ni(II) ions [11], and in a more comprehensive study [14] the binding abilities of the C-terminal 71–76 fragment of histone H4 Ac-ThrTyrThrGluHisAla-amide in which Ni(II) mediated hydrolysis of the peptide bond Tyr-Thr was evident [14], in agreement with previous findings concerning the hydrolytic cleavage of the peptide bond Glu-Thr of the peptide -TETHHK- [9]. …”

The role of terminal amino group and histidine at the fourth position in the metal ion binding of oligopeptides revisited: Copper(II) and nickel(II) complexes of glycyl-glycyl-glycyl-histamine and its N-Boc protected derivative

“…The nickel(II)-induced cooperative deprotonation of 2-3 amide nitrogens of oligopeptides is a well known phenomenon [2,48]. Several examples demonstrate that the cooperative binding of these groups result in a fundamental structural change of the complexes leading from octahedral (high spin) to square planar (low spin) geometry [7,12,[38][39][40][49][50][51][52]. The deprotonation processes of the parent complexes of GGGHa, leading to NiH − 2 L and to NiH − 3 L in a separated third proton release step ( Fig.…”

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

“…However, in our system, the saturation of the coordination sphere that has already occurred prevents the polynuclear complexes formation. On the other hand, the EPR parameters at pH 9.4 (Α || = 192 and g || = 2.204, Table 3) are typical for coordination of Cu(II) ion with a {N Im , 3N − amide } donor set [34,35,55], while the value λ max = 513 nm calculated by the absorption spectra is close with the one predicted from the equation of Sigel and Martin (λ max = 522 nm) [48], considering the presence of one imidazole and three amide nitrogen atoms in copper's coordination sphere. The latter also indicates that the binding of the Asp carboxyl group is no longer present.…”