A coupling mechanism to inter-relate regulatory with haem-haem interactions of haemoglobin.
The Me2+ (Zn2+ or Mg2+)-dependent increase in the oxygenation of Haemoglobin (Hb) is examined theoretically using an overview in scale of the interface of the alpha 1 beta 2 dimer of Hb. A model was developed showing that 2,3 DPG and Me2+ would maintain a pH-modulated mutually exclusive relationship as ligands of Hb because they both share a common binding His-beta (2)143. A symmetric relationship applies to alpha 2 beta 1. One atom of metal, within each dimer, would compete in turn with each of the haem groups to sequentially dislocate both proximal histidines during the transition from deoxyHb to oxyHb. Hence, the pH-modulated reaction path of the multiple equilibrium of Hb would integrate the interactions of either one 2,3 DPG with four histidines for the increase of hindrance effects, or the interactions of two Me2+ with four haem groups to increase their affinity for O2. The model predicts that increases in pO2 would increase the affinity of Hb for Me2+ and therefore for O2, simultaneously decreasing its affinity for 2,3 DPG and protons.
D019794:2,3-Diphosphoglycerate; D001665:Binding Sites; D004163:Diphosphoglyceric Acids / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D011487:Protein Conformation; D013816:Thermodynamics; D015032:Zinc / Q000378:metabolism
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D019794:2,3-Diphosphoglycerate; D006418:Heme; D008274:Magnesium; D015032:Zinc; D010100:Oxygen