Structure and Properties of Hemoglobin Carlem, a Human Hemoglobin Variant with Amino Acid Substitutions in 2 Residues of the β-Polypeptide Chain

Abstract

Abstract A new sickling hemoglobin variant designated hemoglobin Charlem (Hb Ch) migrated slightly anodally to the position of hemoglobin C on electrophoresis at pH 8.6, and has been shown to have the structure αa2 β6 glu → val, 73 asp → asn2. Hemoglobin Ch comprised 40% of the hemoglobin in individuals of two generations of an American Negro family and is the first instance in which two amino acid substitutions in a single polypeptide chain have been defined in a human hemoglobin variant. Hemoglobin Ch appeared not to differ significantly from Hb A in its oxygen equilibria, ultraviolet spectra of the oxy and deoxy forms, and titratable sulfhydryl groups. Probably by virtue of its β6 val substitution, Hb Ch shared with Hb S (αa2 β6 glu → val2) the properties of erythrocyte sickling and relative insolubility and gelation of the deoxyhemoglobin. However, gelation experiments suggested that the β73 asn substitution resulted in a decrease in the intermolecular interactions of deoxyhemoglobin Ch as compared with deoxyhemoglobin S, and implied conformational differences between the two deoxyhemoglobins.