Interactions of transition metal ions with His-containing peptide models of histone H2A

The coordination properties of Ni(II), Cu(II) and Zn(II) ions towards the terminally blocked (CH3CONH- and -CONH2) hexapeptides -TESHHK-, -TASHHK-, -TEAHHK-, -TESAHK- and -TESHAK-, which are all models of the C-terminal "tail" (-ESHH-) of histone H2A, were studied by potentiometric and several spectroscopic techniques (UV/Vis, CD, NMR, EPR). The peptides were chosen in such a way as to compare the effect of Glu, Ser and His residues on the stability, the coordination and hydrolytic abilities of the complexes formed. It was found that all peptides bind to the metal ions initially through one or two imidazole nitrogens in weakly acidic and neutral solutions forming slightly distorted octahedral complexes. At higher pH values, a series of square-planar complexes are formed with Ni(II), which binds simultaneously through an imidazole and three amide nitrogens in an equatorial plane. This proposed conformation includes the participation of only one imidazole nitrogen, in the case of all peptides, in the coordination sphere of Ni(II) ions. Additionally, all peptides coordinate Cu(II) efficiently. At higher pH values, Cu(II) ions coordinate equatorially with the imidazole nitrogen of His-5 or His-4 and three amido nitrogens of the peptides -TESAHK- and TESHAK-, while the second histidine residue of the peptides -TESHHK-, -TASHHK- and -TEAHHK- is additionally bound in the apical position. In contrast, the combination of potentiometric titrations and one- and two-dimensional H-1-NMR suggested no amide coordination in the coordination sphere of Zn(II) ions, over a wide range of pH. In basic solutions, the peptides -TASHHK- and -TESAHK- were hydrolyzed in a Ni(II)-assisted fashion, while no hydrolytic processes were noticed in peptides -TEAHHK- and -TESHAK- where the Ser or His-5 residues are replaced with the Ala residue. Moreover, CuH-1 L complex with -TESHHK- reacts with H2O2 and the resulting reactive oxygen intermediate efficiently oxidizes 2'-deoxyguanosine. (c) 2004 Elsevier B.V. All rights reserved.