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 beta-subunits (in the native form and with the cysteines combined with p-mercuribenzoate), and the respective beta (1-55) peptides have been measured. The results show that in the systems obtained from hemoglobin S there is a group which shifts its pK from about 7.0 to 8.35 in the beta-subunits that were reacted with p-mercuribenzoate and to more than 9.0 in the beta (1-55) peptide. Proton nuclear magnetic resonance measurements indicate that in the peptide beta (1-55) from hemoglobin S this residue is the histidine at beta 2. It is proposed that this pK shift is due to the formation of a salt bridge between beta 2 His and beta 7 Glu. This structure would disrupt the first turn of the A helix of the beta s-subunits. Its stabilization by extramolecular contacts may be relevant to the mechanism of fiber formation of hemoglobin S.