Figure 1.

Schematic representation of hemoglobin (Hb) and its affinity for Oxygen (O₂) in a classic HB-O₂ dissociation curve. (A) The Hb structure has two α- and two β-subunits (light and dark magenta, respectively). Each subunit has a heme residue with Fe⁺². Transition from deoxy-Hb (“T” state) to oxy-Hb (“R” state) is represented from left to right. Increasing concentrations of O₂, changes the structure of hemoglobin to “R” state allowing the cooperative binding of O₂. The transition starts by displacement of H₂O from the distal region of the binding pocket by a diatomic ligand such as O₂. Once the O₂ is sequestered at the distal pocket, the proximity with Fe⁺² from the heme group allows O₂ to bind covalently. Finally, minor electrostatic rearrangements stabilize the new conformation. After this process, the hydrophobic interactions between the other subunits are weakened facilitating bonding between O₂ and the unliganded hemes of the same Hb. (B) Hb saturation curve shows changes in affinity for O₂ by multiple factors. Under low pH, the C-terminal residues of the globin β-chains are protonated, which facilitates O₂ release from heme by shifting the Hb conformation to the low-affinity T-state (12). Similarly, CO₂, Cl⁻, and 2,3-diphoglycerate DPG, bind to multiple cationic residues on the N- and C-termini of the α- and β-chains that ultimately stabilizes the T-state conformation of Hb (13, 14). The specific allosteric shift is represented by the orange dashed line displaced to the right from the continuous blue line. The orange dot shows a reduced affinity observed by a higher P₅₀-value. The opposite is also true, where the allosteric shift to the left by the above-mentioned factors (represented by the green dashed line) increases the affinity of O₂ for Hb, shown by the green dot and the smaller P₅₀-value. Adapted from Storz (15).