Crystal structure of the ferric homotetrameric β₄ human hemoglobin

Spectroscopic studies carried out in the early seventies have shown that the β-homotetramer of human hemoglobin (β₄-HbA) in the ferric state is a mixture of aquomet and bis-histidyl forms. Here we present the first crystal structure, solved at 2.10 Å resolution, of the oxidized form of β₄-HbA. The overall quaternary structure of the protein in the ferric state is virtually indistinguishable from that of the ferrous deoxygenated and carbomonoxy forms. The structure reveals that the four hemes are exclusively in an aquomet coordination, without any trace of bis-histidyl coordination. The oxidation of β₄-HbA is associated with the formation of a disulfide bridge between residues Cys112(G14) of β₁/β₄ and β₂/β₃ chains. The coordination state of β₄-HbA has been compared to that known for other organisms that exhibit bis-histidyl heme coordination in the β₄ state. This occurrence has been discussed in terms of different organism physiology.