Copper(II)‐Binding Ability of Human Alpha‐fetoprotein

Our previous sequence study showed that alpha‐fetoprotein (AFP) had one histidyl residue at position 3 or 4 from the N‐terminus (heterogeneous N‐terminus). Since human serum albumin also has a cupric chelate locus histidine at the third position from N‐terminus, copper(II)‐binding ability of AFP was examined by equilibrium dialysis and gel‐filtration method. AFP could bind one mole of copper(II) ion per mole of protein above pH 6.0 and the pH‐dependence of copper(II)‐binding ability of AFP was quite similar to that of albumin. AFP bound 0.5 mole of copper(II) ion at pH 5.4 which is close to the pK value of imidazole of histidine. Photo‐oxidation of AFP in the presence of methylene blue showed that the loss of copper(II)‐binding ability of the protein was parallel to the destruction of histidine. These results indicate that histidyl residues play some important role in this copper(II)‐binding ability of the protein. Reduced and S‐carboxymethylated AFP also had this ability.