A new hemoglobin variant altering the alpha 1 beta 2 contact: Hb Chemilly alpha 2 beta 2 99(G1)Asp leads to Val.

ABSTRACT

Hemoglobin Chemilly (alpha 2 beta 2 99(G1)Asp leads to Val), a high oxygen affinity variant, was uncovered in the red blood cells of a polycythemic patient who reported to the hospital concerning periodic headaches. We describe the molecular abnormality and functional studies of this new abnormal Hb. beta 99(G1)Asp, an invariant residue of hemoglobin, is considered a key amino acid for conformational changes between the R in equilibrium T quaternary structures responsible for the allosteric behavior of hemoglobin. Hb Chemilly exhibits a high O2 affinity, very low cooperativity and reduced Bohr effect. Its functional abnormalities are compared to the 5 other Hb variants at site beta 99(G1) described up to now of the 7 single base substitutions predictable from the genetic code.