A mutation that changes glutamate to a glutamine residue basically removes a negatively charge and replaces it with a polar uncharged amino acid. This removal of charge drastically affects the intermolecular forces of attraction present in the molecule, most probably vacating a supposedly charged pocket in the tertiary structure of the protein. This causes it to lose the integrity ofthe original tertiary/quaternary structure thereby losing protein activity.
A mutation that changes a glutamate is found to lead to a loss of activity in a protein. However, activity is regained when a second mutation at a different position changes an alanine residue to aspartate. How might this double mutant (E to Q with A to E) lead to a restoration of activity?
Hint: These secondary mutations are sometimes called compensatory mutations.
2nd Hint: Think three dimensionally.
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