Interrelationship Between Structure and Function in Hemoglobin and Myoglobin

Abstract

The combination of the ferrous iron in the heme group with hemoglobin or myoglobin results in the specific and physiologically important property of binding reversibly molecular oxygen giving a stable oxygen derivative. The presence of the ligand to the iron in the fifth coordination position and the presence of surrounding polypeptide chains rich in aromatic side chains is important for this above reaction. The stability of the hemeprotein complex is due to linkages of the protein with the porphyrin part of the heme group. These linkages drastically change the conformation of the globin. The behavior of myoglobin corresponds to a simple model of an oxygen carrier. The basic function, that is, the affinity for the ligand depends uniquely on the interaction of the heme group with its binding site in the native protein. Deviations from the simplest behavior can be seen which may be associated with small changes in conformation in the part of the chain which surrounds the heme on conformation in the part of the chain which surrounds the heme on attachment of the ligand to iron. The state of the heme iron, as in hemoglobin, has a great effect on the denaturation of the protein. The most characteristic aspect of the functional behavior of hemoglobin is that the reactivity of the heme iron is dominated by interactions with other groups of the molecule which may occupy positions distant from the heme group. The binding sites are not independent and the presence of the ligand on some have the effect of increasing the affinity of the remaining ones and thus giving a sigmoid curve. The shape of the equilibrium curves of the other ligands bound to ferrous iron is the same as that of oxygen. This curve also remains the same at different temperatures, but varies with changes in concentration of protein, pH and salt concentration. The Bohr effect consists of the change in the oxygen equilibrium of hemoglobin for changes in pH, and is the expression of a functional interaction between oxygen binding sites and ionizable groups. Its importance lies in its significance as a regulatory mechanism in the oxygen transport and gas exchange, and that it is a beautiful model for effects of pH on the functional properties of proteins in general. There are two aspects of the Bohr effect. One is the change in the oxygen affinity with pH and the other is the change with oxygen saturation of the affinity of the protein for hydrogen ions.