Question

A mutation of chymotrypsin changes the catalytic Asp to Glu. A dramatic decrease in catalytic rate was observed. why might this occur even though the 2 side chains have the same functional group COO-?

Answer 1

The enzyme substrate reactions follow the lock and key mechanism i.e. are very highly specific, just like a particular key fits into a particular lock. The enzymatic activity of chymotrypsin is highly dependant on the catalytic triad (a group of three amino acids, Ser-His-Asp) present at the active site of the enzyme which is responsible for the catalytic activity. The Asp is H-bonded to His which increases the PKa of imidazole nitrogen from 7 to 12, thereby acting as a strong base to activate the serine nucleophile.

In the case of Glu, it has a low PKa and therefore acts as a weak base resulting in low activation of the serine nucleophile and a decrease in activity.