Hemoglobin is a globular protein, which in adults contains two alpha subunits and two beta subunits. The protein is composed of two alpha-beta dimers. These subunits closely resemble myoglobin, a protein with 153 amino acid residues in 8 α-helicies labeled A-H. The alpha subunit has 141 amino acid residues, it lacks helix D and has a shortened helix H. The beta subunit has 146 amino acid residues, and has a shortened helix H.
Each subunit contains a heme molecule, which is an aromatic ring structure that is composed of four pyrrole rings linked by methelyene bridges. The heme group has an iron atom coordinated by the four nitrogen atoms of each pyrrole ring.
The iron atom is in the ferrous, Fe(II), oxidation state. It coordinates six ligands (with oxygen bound) and has an octahedral geometry. If the iron atom is oxidized to the ferric, Fe(III) state, the iron will coordinate a water molecule instead of an oxygen molecule. This oxidation does not occur upon the binding of oxygen when the heme is located in the protein. If it does occur then hemoglobin is called methemoglobin. The enzyme methemoglobin reductase will catalyze the conversion of the iron back to the Fe(II) state.
Iron Ligands
Four Nitrogen atoms of pyrrole rings
Proximal Histidine F8
Oxygen (When bound)
The oxygen binding site is sterically hindered by the distal histidine E7.
The distal histidne plays an important role in carbon monoxide binding. When stripped of protein the heme will bind CO with 25,000 times the affinity of oxygen. In the protein this is reduced to 250 times the affinity. This is due to steric interactions of the distal histidine E7. CO binds optimally at an angle of 90 degrees with respect to the heme plane. Histidine E7 forces CO to bind at a 60 degree angle greatly decreasing its affinity
Hemoglobin exists in two conformational states. The T-state, which has a low affinity for oxygen, and the R-state, which has a high affinity for oxygen. Each state is stabilized by a particular set of forces. Upon oxygen binding the T-state shifts to the R-state and when oxygen unbinds the R-state shifts to the T-state.
These conformational changes occur because in the T-state the Fe atom is located .6 angstroms out of the heme plane. When oxygen binds this pulls the iron in towards the heme plane by .4 angstroms. This causes a shift in the location of the F helix which disrupts the stabilizing interactions of the T-state and forms the stabilizing interactions of the R-state.
Factors Involved in Conformational Shifts
Bohr Effect
Salt Bridges
Carbamylation of the N-Terminus
Binding of Bisphosphoglycerate