Hemoglobin plays an essential role in distibuting oxygen to all the tissues of the body. Hemoglobin if red blood cells binds oxygen as it is pumped through the lungs where [O2] is high. Then as it transits to other parts of the body where the [O2] is low releases it. It it bound oxygen with standed hyperbolic binding curve, We would probably need much more hemoglobin to transport the required amount of oxygen than what we have currently. Fortunately hemoglobin exhibits this cooperaative binding. There are four subunits in the complete enzyme and there are "two" different conformations: one that bonds oxygen poorly; and one that bonds it very well. All four subunits in one molecule of hemoglobin are EITHER in the POOR conformation or in the GOOD conformation. There is rarely a mixture within one molecule. The effect of this will be displayed in a graph on the next page.
On the next page is a series of animations showing the structural changes that take place in hemoglobin as it shifts from the POOR oxygen binding form the other GOOD oxygen binding form. The point here is to notice that overall the structural changes are small. It is not a wholesale refolding of the protein but rather some subtle shifts in amino acid positions. The Heme cofactor actually binds oxygen. It has two shapes: one in which an iron is coplanar with the Heme (the GOOD form); the other where the iron atom is not as coplanar with the Heme (the POOR form). The change in Heme structure is coincident with changes in protein structure. The changes in protein structure are "transmitted" to the subunit next door where the structure of the neighbor subunit changes accordingly.... Thus cooperative structural change.
A molecule present in human blood 2,3 Bisphosphoglycerate inhibits O2 binding to hemoglobin. Its effect is to stabilize the POOR form of the hemoglobin structure. This is an ALLOSTERIC EFFECT. The subject of the next several pages.
First however, let's orient you to some important features of the hemoglobin structure. Below is a couple pictures of the poor oxygen binding form of hemoglobin. to give you a "map" of what to look for in the following animations.
The animations that follow on the next page are all closeups of the HEME, the HIS that is bound ot the iron of the heme and the subunit interface. This is an attempt to describe the mechanism by which proteins can have two different structures: one that catalyzes a reaction very well; one that is substantially less effeicient. RECALL as you look at these that is is NOT substrate binding that CAUSES the structure to change. Rather, both Types of structures are present at all times and are rapidly interconverting. O2 simply shifts the euqilbrium toward the GOOD structure.