1. Serine proteases
Named because they use a serine residue to cut peptide bonds
Possess a catalytic triad
His 57
Asp 102
Ser 195
Use 2 different types of catalysis

3. Mechanism of serine proteases
Step 1: Peptide enters the enzyme’s active site
What happens:
Lone pair of electron on His side chain form bond with H of nearby Ser 195
Ser 195 side chain O performs nucleophilic attack on peptide carbonyl C

4. Step 2: Tetrahedral intermediate is formed
What happens:
Bond formed between N from peptide and H from Ser 195
Peptide carbonyl group reforms
C-N peptide bond is broken

5. Step 3: Covalent intermediate is formed
What happens:
N-terminal portion of cleaved peptide is still bonded to Ser 195

6. Step 4: Water molecule enters active site
What happens:
Lone pair of electrons on His 57 side chain attacks H on water
Bond forms between water O and peptide carbonyl C

7. Step 5: Second tetrahedral intermediate is formed
What happens:
Ser 195 side chain O forms bond with water H, breaking bond to peptide C
Bond between His 57 side chain and H breaks
Peptide carbonyl forms

8. Step 6: Enzyme is regenerated
What happens:
Cleaved peptide has a new C-terminus
Catalytic triad is reset and ready for another round of catalysis
Both acid-base catalysis and covalent catalysis occurred