In most, a single amino acid replacement occurs in either the a or b chain of normal Hb A. Many of these changes cause no known effect, but several lead to pathologies associated with abnormal O 2 transport. First, lets look at HbS or sickle cell hemoglobin. In HbS there is a single amino acid replacement of a Val for Glu at position 6 of the b chain. This seemingly innocuous change places a hydrophobic sidechain on the surface of the protein. Mutant hemoglobins provide unique opportunities to probe structure-function relations in a protein.
Some mutant hemoglobins cause serious illness.
The structure of hemoglobin is so delicately balanced that small changes can render the mutant protein nonfunctional. Thus, the images are not derived from actual crystal structures but represent approximations to what those structures would probably look like. Mutations that lead to loss of heme. The heme group can be dislodged by mutations in the heme binding pocket. In Hb A the Phe blocks access of water to the heme pocket.