Glutamic acid and valine are two amino acids with different molecular structures. (Glutamic acid is a strongly hydrophilic molecule, and the valine is a strongly hydrophobic molecule. This is something you will learn more about in the next activity). Why do you think switching the hemoglobin genes sixth amino acid form the glutamic acid to valine would affect the hemoglobin protein?

The switch from glutamic acid to valine in position 6 of hemoglobin (HB) forms the basis of sickle cell anemia disease pathology.

Valine is hydrophobic and it's chain is shorter than glutamic acid. The lack of the carboxylic acid and shortness of valine will result in loss of the ionic interactions formed between the glutamic acid's carboxylic group and other amino acids. A hydrophobic cavity will form in the beta sheet of HB due to the short and hydrophobic structure of valine. For these reasons, the HB molecule will be less stable and insoluble in water. The insolubility is thought to be caused by fibril formation between the valine interacting with hydrophobic pocket residues of the adjacent HB molecule. This would in turn affect binding of oxygen to HB.