Conformational Changes Upon Binding of Oxygen

Careful examination of Figure 4 shows that the heme group is nonplanar when it is not bound to oxygen; the iron atom is pulled out of the plane of the porphyrin, toward the histidine residue to which it is attached. This nonplanar configuration is characteristic of the deoxygenated heme group, and is commonly referred to as a "domed" shape. The valence electrons in the atoms surrounding iron in the heme group and the valence electrons in the histidine residue form "clouds" of electron density. (Electron density refers to the probability of finding an electron in a region of space.) Because electrons repel one another, the regions occupied by the valence electrons in the heme group and the histidine residue are pushed apart. Hence, the porphyrin adopts the domed (nonplanar) configuration and the Fe is out of the plane of the porphyrin ring (Figure 5, left). However, when the Fe in the heme group binds to an oxygen molecule, the porphyrin ring adopts a planar configuration and hence the Fe lies in the plane of the porphyrin ring (Figure 5, right).

Figure 5 On the left is a schematic diagram showing representations of electron-density clouds of the deoxygenated heme group (pink) and the attached histidine residue (light blue). These regions of electron density push one another apart, and the iron atom in the center is drawn out of the plane. (The nonplanar shape of the heme group is represented by the bent line.) On the right is a schematic diagram showing representations of electron-density clouds of the oxygenated heme group (pink), the attached histidine residue (light blue), and the attached oxygen molecule (gray). The oxygenated heme assumes a planar configuration, and the central iron atom occupies a space in the plane of the heme group (depicted by a straight red line).

The shape change in the heme group has important implications for the rest of the hemoglobin protein, as well. When the iron atom moves into the porphyrin plane upon oxygenation, the histidine residue to which the iron atom is attached is drawn closer to the heme group. This movement of the histidine residue then shifts the position of other amino acids that are near the histidine (Figure 6). When the amino acids in a protein are shifted in this manner (by the oxygenation of one of the heme groups in the protein), the structure of the interfaces between the four subunits is altered. Hence, when a single heme group in the hemoglobin protein becomes oxygenated, the whole protein changes its shape. In the new shape, it is easier for the other three heme groups to become oxygenated. Thus, the binding of one molecule of O₂ to hemoglobin enhances the ability of hemoglobin to bind more O₂ molecules. This property of hemoglobin is known as "cooperative binding."