Oxygen Equilibrium Characteristics of Abnormal Hemoglobins: Hirose (α2β237Ser), L Ferrara (α247Glyβ2), Broussais (α290Asnβ2), and Dhofar (α2β258Arg)

Abstract

The oxygen equilibrium characteristics of four structural variants of hemoglobin A were correlated with their amino acid substitutions. Hemoglobin Dhofar, in which the proline at E2(58)β is replaced by arginine, had normal oxygen equilibrium characteristics. Hemoglobin L Ferrara. in which the aspartic acid at CD5(47)α is replaced by glycine, and hemoglobin Broussais, in which the lysine at FG2(90)α is replaced by asparagine, both showed a slightly elevated oxygen affinity; nevertheless both demonstrated a normal heme-heme interaction and a normal Bohr effect. Hemoglobin Hirose, in which the tryptophan at C3 (37)β is replaced by serine, showed abnormalities of all oxygen equilibrium characteristics; i.e., increased oxygen affinity, diminished heme-heme interaction, and reduced Bohr effect. These results suggest that aspartic acid at CD5(47)α and lysine at FG2(90)α are involved in the function of the hemoglobin molecule, despite the fact that these positions are not located directly in the heme or the α-β-contact regions. Tryptophan at C3(37)β is located at contact between α₁- and β₂-subunits. It is suggested that the substitution by serine might disturb the quarternary structure of the mutant hemoglobin molecule during transition from oxy-form to deoxy-form resulting in an alteration of the heme function.