Structure and properties of hemoglobin C-Harlem, a human hemoglobin variant with amino acid substitutions in 2 residues of the beta-polypeptide chain.

A new sickling hemoglobin variant designated hemoglobin &arlem (Hb C,) migrated slightly anodally to the position of hemoglobin C on electrophoresis at pH 8.6, and has been shown to have the structure (rt fll G1u + ““n I3 *w’ Asn. 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 Cn 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 f16 “*l substitution, Hb CH shared with Hb S (at Pz 6 G1u * Val) the properties of erythrocyte sickling and relative insolubility and gelation of the deoxyhemoglobin. However, gelation experiments suggested that the 073 A8n 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.