Allosteric interactions in non-alpha chains isolated from normal human hemoglobin, fetal hemoglobin, and hemoglobin Abruzzo (beta143 (H21) His replaced by Arg).
Oxygen-linked effects of inositol hexaphosphate occur in heme-containing non-alpha chains isolated from normal human hemoglobin, fetal hemoglobin, and the abnormal human hemoglobin Abruzzo, beta143(H21) His leads to Arg. The occurrence of these effects implies that the chains undergo ligand-linked conformational changes. Inositol hexaphosphate lowers the oxygen affinity of isolated beta and gamma chains by differential binding to their deoxy conformations. Neither 2,3-diphosphoglycerate nor inorganic phosphate produces such an effect. In the case of Abruzzo beta chains, the binding of inorganic phosphate and 2,3-diphosphoglycerate is also oxygen-linked. Stripped beta chains isolated from hemoglobin Abruzzo have much higher oxygen affinity than beta chains isolated from HbA. Their higher oxygen affinity and enhanced allosteric interactions with phosphates account, in large part, for the abnormal functional behavior of the hemoglobin Abruzzo tetramer. In this hemoglobin variant the substitution of arginine for histidine at beta143 involves a residue known to interact with anionic allosteric effectors of hemoglobin. It is of interest that the effect of inositol hexaphosphate observed with isolated gamma chains is comparable to the effect observed with isolated beta chains, even though the gamma143 position is occupied by an uncharged serine residue.
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine; D002248:Carbon Monoxide / Q000097:blood; D004163:Diphosphoglyceric Acids / Q000097:blood; D005260:Female; D005319:Fetal Hemoglobin; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D006639:Histidine; D007558:Italy; D007700:Kinetics; D046911:Macromolecular Substances; D010100:Oxygen / Q000097:blood; D010833:Phytic Acid / Q000097:blood; D011247:Pregnancy; D011485:Protein Binding; D011487:Protein Conformation; D013997:Time Factors
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D046911:Macromolecular Substances; D006639:Histidine; D010833:Phytic Acid; D002248:Carbon Monoxide; D005319:Fetal Hemoglobin; D001120:Arginine; D010100:Oxygen