Question

Suppose that an aspartic acid (aspartate) residue in the active site of an enzyme was mutated to alanine. As expected, the alanine mutant was inactive, suggesting that the aspartic residue was critical to the catalytic mechanism. Which mutation is most likely to restore wild-type level of activity to the alanine mutant?

a. A to Y
b. A to E
c. A to L
d. A to M
e. A to K

Answer 1

b. A to E

Step-by-step explanation:

The aspartic acid (aspartate) residue in the active site of the enzyme is likely critical to the catalytic mechanism because it is a charged amino acid and can participate in ionic interactions that stabilize the transition state of the catalyzed reaction. Since the alanine mutant is inactive, we need to introduce a charged amino acid at this position to restore the activity.

Out of the options given, the mutation that is most likely to restore the wild-type level of activity to the alanine mutant is (b) A to E. The glutamic acid (glutamate) amino acid is similar to aspartic acid in its chemical properties, as both are negatively charged amino acids. Therefore, introducing a glutamic acid residue at the mutated position is likely to restore the ionic interaction necessary for catalytic activity.