C N O Fe
Without bound oxygen (“deoxy”), heme is slightly bowl-shaped, because the Fe++ ferrous ion is too large to fit between the four nitrogens in heme. The binding of O₂ reduces the size of the iron ion enabling a planar conformation, pulling histidine 87, and the alpha helix to which it belongs, towards the heme (Ref. 3A). This slight movement of the histidine has conformational consequences important for cooperative binding of oxygen to the other hemes in the tetrameric protein molecule.
ROTATE the animation to see other views!

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  Here is the same transition with all atoms at their full spacefilling sizes (van der Waals radii).

In the lungs, the neutral pH and low [CO₂] cause hemoglobin to have a high affinity for oxygen, the so-called relaxed (R) form*. Also, oxygen binding is cooperative: oxygen binding to the first two hemes causes the other two to adopt higher oxygen-affinity conformations.

When the oxygen-loaded hemoglobin arrives in the tissues, lower pH, higher [CO₂], and the presence of 2,3-diphophoglyceric acid change it to lower affinity for oxygen, facilitating the release of oxygen. The deoxy conformation is called the taut (T) form*. (Ref. 5)

*To remember which is R and which is T, think of R as Red (oxygenated).

  Oxy↔Deoxy transition (R↔T) of the hemoglobin tetramer. Alpha chains are shown in lighter colors; beta chains, darker. Alpha Beta   Alpha Beta
Heme: C O N Fe During the transition, alpha-beta pairs move as units. One alpha-beta pair rotates 15° relative to the other alpha-beta pair. A movie by Janet Iwasa (link below) shows molecular oxygen binding to individual chains and inducing the transition.

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  The transition from oxy to deoxy moves the beta chain C-terminus about 9 Å closer to alpha chain Lysine 40, forming two salt bridges that help to hold the oxygen-releasing conformation. Here, these amino acids are simplified to spheres. Alpha Beta   Alpha Beta
Heme: Oxy↔Deoxy Alpha chains are shown in lighter colors; beta chains, darker.

  Detailed view of the two deoxy-form salt bridges described in View 4. Alpha Beta   Alpha Beta
Heme: Deoxy The higher pH in the lungs reduces the charge on Histidine, weakening its salt bridge and favoring the oxygen binding conformation. (See Chapter 5, View 3)

  Oxy↔Deoxy transition (R↔T) of the hemoglobin tetramer. Alpha chains are in lighter colors; beta chains are darker. Alpha Beta   Alpha Beta
Heme: Oxy↔Deoxy During the transition, alpha-beta pairs move as units. The alpha-beta pair rotates 15° relative to the other alpha-beta pair. A movie by Janet Iwasa (link below) shows molecular oxygen binding to individual chains and inducing the transition.

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Rotate View 6 with your mouse until the two beta chains (the darker colors) are in front. Notice that there is no space between the beta chains in the Oxy form, but that a space between the beta chains opens up in the Deoxy conformation.

  2,3-diphosphoglycerate (DPG): C O P
Alpha Beta   Alpha Beta
Heme: Oxy, Deoxy Alpha chains are light; beta chains are dark.
DPG, a compound present in red blood cells, binds in the space between the beta chains, and stabilizes the T conformation, which has an allosteric effect facilitating the release of O₂ (Refs. 4, 5). At high altitudes, or when a person suffers from anoxia for other reasons, the concentration of DPG increases, facilitating release of O₂ in tissues.