Relation between allosteric effects and changes in the energy of bonding between molecular subunits

Allosteric effects (dependencies of the ligand affinity of certain specific ligand binding sites on the state of other ligand binding sites) which occur in a protein with multiple subunits but not in the isolated subunits can all be expressed in terms of changes in the inter-subunit bonding energy that must occur during ligand attachment. Co-operative allosteric interactions such as the heme-heme interaction in hemoglobin require that the change in inter-subunit bonding energy accompanying the attachment of a ligand be not uniform but depend rather on the extent to which the protein is already liganded. It is suggested that changes in the energy of subunit bonding may be the primary co-operative parameter. With these considerations in mind, the equilibrium and kinetic constants for the reactions of hemoglobin and of the isolated chains of hemoglobin with oxygen and carbon monoxide are compared and some conclusions are drawn about the structural basis of the heme-heme interaction. At pH 7 and 20 °C the interaction energy between the chains in hemoglobin decreases by 8 kcal./mole hemoglobin when the molecule is saturated with ligand. Since the ligand reactivity of fully liganded hemoglobin is very similar to that of the isolated chains, it is postulated that in deoxyhemoglobin the chains exist in a strained conformation which has a low ligand affinity but permits a higher inter-chain interaction energy. The presence of a ligand raises the free energy of this conformation and therefore reduces the interchain bonding energy.