Conformational changes in the hemoglobin S system as seen by proton binding

The proton binding behavior of the carbon monoxy derivatives of hemoglobins A and S, the respective β-subunits (in the native form and with the cysteines combined with p-mercuribenzoate), and the respective β(1-55) peptides have been measured. The results show that in the systems obtained from hemoblobin S there is a group which shifts its pk from about 7.0 to 8.35 in the β-subunits that were reacted with p-mercuribenzoate and to more than 9.0 in the β(1-55) peptide. Proton nuclear magnetic resonance measurements indicate that in the peptide β(1-55) from hemoglobin S this residue is the histidine at β2. It is proposed that this pK shift is due to the formation of salt bridge between β2 His and β7 Glu. This structure would disrupt the first turn of the A helix of the β(S)-subunits. Its stabilization by extramolecular contacts may be relevant to the mechanism of fiber formation of hemoglobin S.