In the closely packed interior of the tertiary structure of an enzyme, alanine w
ID: 487984 • Letter: I
Question
In the closely packed interior of the tertiary structure of an enzyme, alanine was changed by mutation to a valine, leading to loss of enzyme activity, although that residue was not directly involved in catalytic function of the enzyme. However, activity was partially regained when an additional mutation at a different position in the primary structure changed an isoleucine to glycine, explain how the first mutation Ala-Val likely caused a loss of activity and the second mutation in another region of the protein, Ile -> Gly, resulted in a partial recovery of enzyme activity.
Explanation / Answer
First mutation is Ala to Val. This causes a loss of function. The second mutation, at a different amino acid, is a change of Ile to Gly. When the Val and the Gly are both present, activity is restored. They are all nonpolar, but have different sizes. Valine is bigger than alanine, so the loss in activity must be caused by this change in size. Glycine is smaller than isoleucine and this change, in conjuction with the first, helps restore activity. The amino acid side chains are often packed tightly together. These data indicates that the alanine was packed into the protein somewhere near the isoleucine. The valine is too big and causes disruptions in the protein structure that lead to the loss in activity. When the isoleucine is changed to glycine, the change in size to a smaller amino acid must compensate for the earlier change and make room for the valine to fit in the protein. So, overall, there is now space for all of the amino acids in the protein once again, and activity is restored.