Electrostatic contributions to the energetics of dimer-tetramer assembly in human hemoglobin: pH dependence and effect of specifically bound chloride ions.
The pH dependence and effects of specifically bound chloride ions on the electrostatic contribution to the energetics of human hemoglobin dimer-tetramer assembly were computed for deoxy- and liganded hemoglobin. In the absence of bound chloride, the electrostatic contribution models the observed contrasting pH dependence of dimer-tetramer assembly for deoxy- and oxyhemoglobin. The effect of specifically bound chloride on the computations depends on the number and placement of the anions. Deoxy assembly shows a greater sensitivity to anion binding, with effects propagating as far as 32 A from the binding site. This sensitivity suggests a mechanism for electronic communication with the heme. At pH 7.4, 24-34% of the experimental value for deoxy and 73-85% for oxy dimer-tetramer assembly stabilization are predicted. Together with the findings of Chu and Ackers [Chu, A. H., & Ackers, G. K. (1981) J. Biol. Chem. 256, 1199] and other recent work, these results suggest that salt bridge formation is not the dominant energetic factor favoring deoxyhemoglobin dimer-tetramer assembly. Results of this work suggest that the marked electrostatic stabilization favoring oxy dimer-tetramer assembly may be a significant contributor to the quaternary enhancement observed in assembly reactions whereas the nonelectrostatic factors favoring deoxy dimer-tetramer assembly may be largely responsible for quaternary constraint.
D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D002712:Chlorides / Q000097:blood*; D004563:Electrochemistry; D006454:Hemoglobins; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010108:Oxyhemoglobins; D011108:Polymers; D011485:Protein Binding
D002712:Chlorides; D006454:Hemoglobins; D010108:Oxyhemoglobins; D011108:Polymers