HEMOGLOBIN GREAT-LAKES (BETA-68 [E12] LEUCINE-]HISTIDINE) - A NEW HIGH-AFFINITY HEMOGLOBIN

  • 1 January 1981
    • journal article
    • research article
    • Vol. 58  (4) , 813-817
Abstract
Great Lakes, .beta.68 (E12) Leu .fwdarw. His, is a new high O2 affinity Hb variant discovered in a 29-yr-old patient having numerous hospitalizations for thrombophlebitis associated and mild erythrocytosis. The mutant Hb has normal stability and normal electrophoretic mobility, but increased O2 affinity (P-50 16.1 mm Hg at 37.degree. C, pH 7.4) and reduced cooperativity. The abnormal .beta.-chain could be separated on globin chain chromatography on carboxymethyl/cellulose in spite of the normal electrophoretic mobility of the intact Hb. The leucyl residue at .beta.68th position (E12) is in the middle of E-helix, which is part of the heme pocket and next to the valine (E11), which is the heme binding site. The substitution of proline for leucine in Hb Mizuho resulted in the distortion of tertiary structure of the .beta.-chains and lead to a serious instability of Hb molecule. The substitution of this residue by histidine in Hb Great Lakes is not associated with Hb instability.