Inorganic and Analytical Chemistry, University of Debrecen, H-4032, Debrecen, Egyetem tér 1, Hungary.
Department of Applied Chemistry, University of Debrecen, H-4032, Debrecen, Egyetem tér 1., Hungary.
Chembiochem. 2024 Oct 16;25(20):e202400475. doi: 10.1002/cbic.202400475. Epub 2024 Sep 12.
Interactions between metal ions and proteins are considered reversible, such as the coordination of a metal ion to a protein or enzyme, but irreversible processes like the oxidative reactions, aggregation or hydrolytic processes may occur. In the presence of Ni(II)-ions selective hydrolysis of the peptides containing the -SXH- or -TXH- motif was observed. Since the side chain of histidine serves as the metal ion binding site for many native proteins, and very often histidine is present in a -SXH- or -TXH- sequence, to study the complex formation and hydrolytic processes in presence of nickel(II) ion four peptides were synthesised: Ac-SKHM-NH, ASSH-NH, ASSH-NH, AAAϵKSH-NH. The Ni(II)-induced hydrolysis of Ac-SKHM-NH peptide occurs rapidly in alkaline medium already at room temperature. In two peptides containing -SSH- sequence on the C-termini, the N-terminal part is the major binding site for the nickel(II) ion, but the formation of dinuclear complexes was also observed. In the [NiLH] complex of hexapeptide, the coordination sphere of the metal ions is saturated with deprotonated Ser-O, which does not result in hydrolysis of the peptide. For ASSH-NH, both Ni(II) ions fulfill the conditions for hydrolysis, which was confirmed by HPLC analyses at pH ≈8.2 and 25 °C.
金属离子与蛋白质之间的相互作用被认为是可逆的，例如金属离子与蛋白质或酶的配位，但也会发生不可逆过程，如氧化反应、聚集或水解过程。在 Ni(II)-离子存在下，观察到含有-SXH-或-TXH-基序的肽的选择性水解。由于组氨酸的侧链是许多天然蛋白质的金属离子结合位点，并且组氨酸经常存在于-SXH-或-TXH-序列中，因此为了研究镍(II)离子存在下的络合和水解过程，合成了四种肽：Ac-SKHM-NH、ASSH-NH、ASSH-NH 和 AAAϵKSH-NH。在碱性介质中，即使在室温下，Ac-SKHM-NH 肽也会迅速发生 Ni(II)-诱导的水解。在两个 C 末端含有-SSH-序列的肽中，N 末端是镍(II)离子的主要结合位点，但也观察到双核络合物的形成。在六肽的[NiLH]络合物中，金属离子的配位球被去质子化的 Ser-O 饱和，这不会导致肽的水解。对于 ASSH-NH，两个 Ni(II)离子都满足水解的条件，这通过在 pH≈8.2 和 25°C 下的 HPLC 分析得到了证实。
