In: Chemistry
1. You are working with chymotrypsin, and you mutate the Ser-195 to Alanine and see a 106–fold decrease in activity. You also, separately, mutate His-57 to Alanine and see a similar decrease in activity.
a. Draw the original, whole chymotrypsin mechanism concerning the wild type catalytic triad. Make sure to label the the N and C terminal ends of the peptide being cleaved, as well as the new N and C termini formed.
b. Draw the catalytic triad with the S195A mutation, and then the catalytic triad with the H57A mutation, instead. Explain which interactions are lost, compared to the original catalytic triad. A new student in your lab creates a chymotrypsin double mutant, with both Ser and His being mutated to Ala at the same time. The student says that since the activity, individually, decreases 106 fold, together, it should decrease activity 1012-fold.
c. Is this conclusion correct? Why or why not?