Question

Genetic mutations occasionally occur in the genes for glycolytic enzymes. If a particular mutation occurred in which a serine was substituted for a proline in the protein sequence, what are three distinctly different hypothetical effects that could arise from this mutations that could result in reduced enzyme activity? Please justify your hypothesis using molecular terms.

Answer 1

As Serine is generally considered a slightly polar polar, amino acid with small side chain, is fairly act as neutral molecule for the mutation. In experimental biology it is generally replace with the small polar amino acid such as threonine. Since the mutation has occurred and the serine is being replaced by the proline it will cause following impacts on the protein activity:

1. Generally serine occurs at the active catalytic site of the enzyme in triad of Asp-His-Ser, now substitution will disturb this triad in most of the proteins and since it is at active site the activity of the enzyme will lose.
2. Serine is the amino acid which has ability to get phosphorylate, substitution with proline will cause loss of phosphorylation and hence will not able to get activated by other proteins.
3. Proline is generally known as helix breaker, therefore replacement with proline can disturb the secondary structure of the protein and hence the overall structure may get affected.
4. Serine usually occurs inside or outside of the protein surface and helps to make interactions with the polar environment, substitution will also affect this.