Chymotrypsin

Phase 1 - Step 1

Asp-102, His-57, and Ser-195 form the “catalytic triad”

Asp-102 makes His-57 a better general base in the first step

Phase 1 Step 2

His-57 acts as a general base to deprotonate the hydroxyl group of Ser-195 and make it a better nucleophile

Ser-195 acts as a nucleophile and attacks the carbonyl group forming a covalent bond with the carbonyl carbon = covalent catalysis

Phase 1 Step 3

The short-lived intermediate: Protonated

His-57 now acts as a general acid to

protonate the amine leaving group

Next the peptide bond is broken and the C-

terminal end of the polypeptide chain leaves

(Product 1)

The acyl-enzyme intermediate is formed

completing the first phase of the reaction

Phase 2 Step 4

Water enters the enzyme

active site, where the C-

terminal end of the polypeptide

used to be located.

Phase 2 Step 5

His-57 acts as a general base to deprotonate water and make it more nucleophilic and water acts as a nucleophile and attacks the carbonyl carbon

Phase 2 Step 6

Protonated His-57 acts as a general acid to protonate the Ser-195 leaving group

Ser-195 cleaves from the N-terminal end of the polypeptide (to regenerate the enzyme)

Phase 2 Step 7

The final product (the N-terminal end of the original polypeptide) leaves.

The enzyme is now returned to its original form