Structure of human foetal deoxyhaemoglobin.

The structure of human foetal deoxyhaemoglobin F II has been solved at a resolution of 2·5 A. Phase angles were determined by a single isomorphous replacement with paramercuribenzoate combined with the molecular replacement method, using the atomic co-ordinates of deoxyHbA determined by Fermi (1975) . A difference Fourier electron density map of deoxyHbF—A is largely featureless except where the amino acid sequences of the two proteins differ, and at positions occupied by bound solvent molecules which were not included in the phase calculations. These occur in the same positions between neighbouring subunits as in deoxyHbA. The only detectable differences between the tertiary structures of the β and γ-chains occur in the two N-terminal segments. In the γ-chain the NA segment is further from the EF segment and from the H helix, and the A helix is closer to the E helix than in the β-chains. As a result of the former change, an anion bound between Vallβ and Lys82β in deoxyHbA is absent from deoxyHbF, and the distances from the two phosphate groups of 2,3-diphosphoglycerate to Hienβ may be increased in deoxyHbF, which may contribute to the lower affinity of foetal deoxyHbF for 2,3-diphosphoglycerate. The reduction of the distance between helices A and E is similar to that which occurs in deoxyhaemoglobin on addition of organic phosphates, where it apparently tightens up the structure and lowers its intrinsic oxygen affinity. It may be responsible for the lower oxygen affinity of “stripped” haemoglobin F compared to A. Although deoxyHbA and F crystallize in different space groups, both crystals are made up of filaments of molecules stacked parallel to the molecular X -axis. The intermolecular contacts between neighbouring molecules along the filament are the same except for the weakening of one electrostatic interaction which may contribute to the higher solubility of deoxyHbF, and to its antisickling effect.