Question

A genetic mutation results in the formation of a hemoglobin molecule in which the HisF8 residue has been replaced with alanine.  In theory, how will hemoglobin’s ability to deliver oxygen be affected or not affected? Be sure to provide a rationale for your answer.

Answer 1

Hemoglobin is a globular protein that transports oxygen via the blood stream to different tissues and organs throughout the body. As its name suggests, hemoglobin has a heme (Iron) prosthetic groups embedded in a bed of globular proteins. Hemoglobin transports oxygen from the lung by binfinbto it through cooperative associations. This means that the binding of one oxygen molecule induces comformational changes in the transition states of hemoglobin from tge Tensed (T) to Relaxed(R) state, which facilitates binding of subsequent oxygen molecules and finally its transport.

In the stereochemical model of hemoglobin structure proposed by Max Perutz, the presence of the Fe-Histidine (HisF8) bond plays an important role in allosteric T to R transitions as well as in cooperative binding of the ligand oxygen. A disruption in this bond causes significant reduction in allosterism and cooperative binding of oxygen to hemoglobin. Thus, substitution of alanine in the place of the highly conserved HisF8 bond causes loss of binding of oxygen to hemoglobin and defects in its transport.