Human normal adult hemoglobin (Hb) A, the oxygen carrier of blood, is a tetrameric protein consisting of two α chains of 141 amino acid residues each and two β chains of 146 amino acid residues each. Each Hb chain contains a heme group which is an iron complex of protoporphyrin IX. Under physiological conditions, the heme-iron atoms of Hb remain in the ferrous state. In the absence of oxygen, the four heme-irom atoms in Hb A are in the highspin ferrous state [Fe(II)] with four unpaired electrons each. Each of the four heme-iron atoms in Hb A can combine with an O2 molecule to give oxyhemoglobin (HbO2) in which the iron atom is in a low-spin, diamagnetic ferrous state. The oxygen binding of Hb exhibits sigmoidal behavior, with an overall association constant expression giving a greater than first-power dependence on the concentration of O2. Thus, the oxygenation of Hb is a cooperative process, such that when one O2 is bound, succeeding O2 molecules are bound more readily. Hb is an allosteric protein, i.e., its functional properties are regulated by a number of metabolites [such as hydrogen ions, chloride, carbon dioxide, 2,3-diphosphoglycerate (2,3-DPG)] other than its ligand, O2. It has been used as a model for allosteric proteins, and indeed, hemoglobins of vertebrates are among the most extensively studied allosteric proteins. Their allosteric properties are physiologically important in optimizing O2 transport by erythrocytes. The large number of mutant forms of Hb available provides an array of structural alterations with which to correlate effects on function. For details, see DickersonandGeis (1983), Bunnand Forget (1986), Ho (1992), Ho and Perussi (1994). There are two types of contacts between the α and β subunits of Hb (Perutz, 1970; Dickerson and Geis, 1983). The α1β1 (or α2 β2) contacts, involving B, G, and H helices, and GH corners, are called packing contacts. These contacts remain unchanged and hold the dimer together even when there is a change in the ligation state of the heme.
Roles of Amino Acid Residues in Woolly Mammoth Hemoglobin on the Temperature Effect of Oxygen Binding
