Crystal structure of the ferric homotetrameric β4 human hemoglobin

Biophys Chem. 2018 Sep:240:9-14. doi: 10.1016/j.bpc.2018.05.003. Epub 2018 May 23.


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 β14 and β23 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.

Keywords: Aquomet; Bis-hystidyl; Crystallography; Hemoglobin.

MeSH terms

  • Crystallography, X-Ray
  • Disulfides / chemistry
  • Heme / chemistry
  • Hemoglobins / chemistry*
  • Humans
  • Models, Molecular
  • Protein Structure, Quaternary
  • Protein Subunits / chemistry


  • Disulfides
  • Hemoglobins
  • Protein Subunits
  • Heme