Electrostatic effects in hemoglobin: electrostatic energy associated with allosteric transition and effector binding.
The pH dependence of the summed electrostatic stabilization for deoxy- and liganded hemoglobin was computed for several ionic strength values. The computed contribution to the stabilization of deoxyhemoglobin by binding of 2,3-diphosphoglycerate in the beta cleft compared well with experimental binding behavior for human hemoglobin A0 and hemoglobin F. The contribution of diphosphoglycerate binding to the alkaline Bohr effect was computed correctly for both hemoglobins A0 and F. The computed effects of simultaneous binding of diphosphoglycerate and formation of Val-1 beta carbamino adducts suggested a competition between these effectors. A direct competition was formulated between these two effectors, with extension to include a simple anion such as chloride or bicarbonate binding in competition with diphosphoglycerate but not with Val-1 beta carbamino formation. This model was found to hold at pH 7.3-7.4 over a range of concentrations of the effectors involved and to predict the pH dependence of Val-1 beta carbamino formation over the pH range 7.0-8.0. The pH dependence of the computed differential stability of liganded vs. unliganded hemoglobin A compared well with observation.
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D004163:Diphosphoglyceric Acids; D005319:Fetal Hemoglobin; D006441:Hemoglobin A; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D046911:Macromolecular Substances; D009994:Osmolar Concentration; D011485:Protein Binding; D011487:Protein Conformation; D013816:Thermodynamics
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D046911:Macromolecular Substances; D006441:Hemoglobin A; D005319:Fetal Hemoglobin