Stray Cu(II) may cause oxidative damage when coordinated to the -TESHHK- sequence derived from the C-terminal tail of histone H2A.
CH(3)CO-Thr-Glu-Ser-His-His-Lys-NH(2), a hexapeptide representing the 120-125 sequence of histone H2A, coordinates Cu(II) ions efficiently. Monomeric complexes are formed. In the major complex at physiological pH, CuH(-1)L, Cu(II) is coordinated equatorially through the imidazole nitrogen of the His-4 residue and the amide nitrogens of the Ser-3 and His-4 residues, and axially through the imidazole nitrogen of the His-5 residue. This complex reacts with H(2)O(2) and the resulting reactive oxygen intermediate efficiently oxidizes 2'-deoxyguanosine. The underlying mechanism involves the formation of Cu(III) and a metal-bound hydroxyl radical species.
Mylonas
M
M
University of Ioannina, Department of Chemistry, Ioannina 45110, Greece.
Malandrinos
G
G
Plakatouras
J
J
Hadjiliadis
N
N
Kasprzak
K S
KS
Krezel
A
A
Bal
W
W
D003300:Copper / Q000737:chemistry*; D005609:Free Radicals; D006657:Histones / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress
D005609:Free Radicals; D006657:Histones; D009842:Oligopeptides; D016877:Oxidants; D003300:Copper; D006861:Hydrogen Peroxide