Question

When an oxygen molecule binds to hemoglobin, substantial evidence shows that the iron(II) changes from a low spin d6 state to a high spin state. How might this affect the size of the iron cation and its ability to fit in the square planar site in heme? Evidence shows that this size change is what initiates the cooperative interaction among the four heme sites in the protein.

Answer 1

Haemoglobin is found in blood and is used to transport oxygen to various body parts. It combines with oxygen to horm oxyhaemoglobin.

Hb + O2 <------> HbO2

Haemoglobin is a tetrameric protein with astounding molecular weight of about 64,500 u. It is a four part molecule which is a protein & embedded in it four planar structure called heme group. In each heme, four nitrogen atoms are coordinated to an Fe²⁺ cation to form square planar array. Directly beneath the iron cation, a histidine group, derived from protein infrastructure of molecule, occupies fifth state. The sixth position around iron is availabe to transport oxygen molecule from lungs to various cell that need it.

A bent structure consistent with oxygen donating one of its lone pair to iron is thought to be the binding which take place in heme. The ability of each heme group to take up oxygen molecule depend on how many of the other three groups are coordinated to oxygen molecule, that is, four heme group seems to bind oxygen molecule cooperatively. When one heme group takes on oxygen , other group become even more receptive to the binding of second oxygen. The binding of one oxygen, open up channel, making it easier for succeding oxygen molecule to make their way to other heme group.

Once O2 is bound to an active site on the hemoglobin molecule, the iron atom (Fe2+) is oxidized to (Fe3+). The interaction that results between iron and oxygen in hemoglobin is a combination of resonance structures, one with (Fe2+)and O2 and another between (Fe3+) and super ion O2.-

The binding of O2 to the iron center results in a conformational change in the histidine residue toward the porphyrin in the structure of the hemoglobin molecule which ultimately results in an increase O2 affinity of hemoglobin. The associated movement of the histdine-containing group will result in a conformational change to the rest of the hemoglobin structure. The COO- group is now interacting with the alpha-beta interface which causes conformational changes of neighboring active sites. These conformational changes will result in an increase of O2 affinity to hemoglobin.

Reason for conformation change:

In the absence of bound O2, the Fe2+ lies slightly to one side of the porphyrin ring, which itself is slightly curved. As a molecule of O2 binds to the heme prosthetic group it pulls the Fe2+ into the plane of the porphyrin ring, flattening out the ring in the process. Movement of the Fe2+ causes the proximal histidine to move also. This, in turn, shifts the position of helix and regions of the polypeptide chain at either end of the helix. Thus, movement in the center of the subunit is transmitted to the surfaces, where it causes the ionic interactions holding the four subunits together to be broken and to reform in a different position, thereby altering the quaternary structure,leading to the cooperative binding of O2 to Hb.