Energetics of subunit assembly and ligand binding in human hemoglobin.
An extensive and self-consistent set of thermodynamic properties has recently been established for the coupled processes of subunit assembly and ligand binding (oxygen and protons) in human hemoglobin. The resulting thermodynamic values permit a consideration of the possible sources of energetic terms accounting for stability of the tetrameric quaternary structures at different stages of ligation, and of the possible sources of cooperative energy. The analysis indicates that: (a) The change in buried surface ara upon oxygenation (i.e., hydrophobic stabilization) does not play a dominant role in stabilizing the unliganded tetramer relative to the liganded tetramer. (b) The pattern of enthalpic and entropic contributions to the free energies of dimer-tetramer. (c) The thermodynamic results are consistent with a dominant role of increased hydrogen bond formation in the deoxy quaternary structure. (d) Within tetramers the variation in free energy for successive oxygenation steps arises from both enthalpic and entropic contributions and the enthalpic contributions are almost entirely attributable to the heats of Bohr proton release. At pH 7.4 the pattern of thermodynamic values suggests that a large contribution to the free energy of cooperativity may arise from the energetics of Bohr proton release. It is suggested that a combination of proton ionization and hydrogen bonding may account for the main energetic features of cooperativity. Possible contributions from fluctuation behavior cannot presently be evaluated.
D001665:Binding Sites; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D010108:Oxyhemoglobins / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents; D013816:Thermodynamics
D006454:Hemoglobins; D008024:Ligands; D046911:Macromolecular Substances; D010108:Oxyhemoglobins; D012997:Solvents