Zoroddu Maria Antonietta, Schinocca Laura, Kowalik-Jankowska Teresa, Kozlowski Henryk, Salnikow Konstantin, Costa Max
Department of Chemistry, University of Sassari, Via Vienna 2, 07100 Sassari, Italy.
Environ Health Perspect. 2002 Oct;110 Suppl 5(Suppl 5):719-23. doi: 10.1289/ehp.02110s5719.
Ni(II) compounds are well known as human carcinogens, though the molecular events which are responsible for this are not yet fully understood. It has been proposed that the binding of N(II) ions within the cell nucleus is a crucial element in the mechanism of carcinogenesis. The most abundant proteins in the cell nucleus are histones, and this makes them the prime candidates for this role. This article is a review of our recent studies of histone H4 models of Ni(II) binding. We analyzed the sequence of the N-terminal tail of the histone H4, Ac-SGRGKGGKGLGKGGAKRH(18)RKVL-Am, for Ni(II) binding. This site has been proposed mainly because of the potent inhibitory effect of Ni(II) on the acetylation of lysine residues near the histidine H(18), and also because of the accessibility of the H4 tail in the histone octamer. Combined potentiometric and spectroscopic studies showed that the histidine 18 acted as an anchoring binding site for metal ions in the peptide investigated. Comparison with the results for Cu(II) binding are also reported. The results allowed us to propose that the binding of Ni(II) is able to promote a secondary structure with organized side-chain orientation on the N-terminal tail of histone H4.
镍（II）化合物是众所周知的人类致癌物，尽管其致癌的分子机制尚未完全明确。有观点认为，镍（II）离子在细胞核内的结合是致癌机制中的关键因素。细胞核中含量最丰富的蛋白质是组蛋白，这使其成为发挥此作用的主要候选对象。本文是对我们近期关于镍（II）结合的组蛋白H4模型研究的综述。我们分析了组蛋白H4的N端尾序列，即乙酰化的-SGRGKGGKGLGKGGAKRH(18)RKVL-Am，以研究镍（II）的结合情况。提出这个位点主要是因为镍（II）对组氨酸H(18)附近赖氨酸残基乙酰化有强烈抑制作用，还因为组蛋白八聚体中H4尾的可及性。结合电位滴定和光谱研究表明，在所研究的肽中，组氨酸18作为金属离子的锚定结合位点。还报道了与铜（II）结合结果的比较。这些结果使我们提出，镍（II）的结合能够促进组蛋白H4 N端尾上具有有序侧链取向的二级结构形成。
