Chapter 9: Catalytic Strategies

Question 1

Serine proteases

Answer 1

Have a catalytic triad of serine, histidine, and aspartic acid linked by hydrogen bonds

Catalyze peptide hydrolysis in a mechanism with two tetrahedral intermediates

Question 2

Aspartic proteases

Answer 2

Mechanism involves one aspartate residue abstracting a proton from a water molecule which then engages in a nucleophilic attack on the carbonyl carbon atom in the peptide bond

Other aspartic acid residue serves as an acid and donates a proton, forming the tetrahedral intermediate

Question 3

Acid‑base catalysis

Answer 3

Involves proton transfer to stabilize intermediates

Amino acids that have side chains with pK_a values near physiological pH may be used as acid or base catalysts

• E.g., Asp, Glu, His, Lys, and Cys, among others, can act as proton donors or acceptors

Question 4

covalent catalysis

Answer 4

A temporary covalent bond forms between the nucleophilic functional group of an enzyme and the substrate, yielding the intermediate

Covalent catalysis is a two part process involving the formation of the intermediate and the breakdown of the intermediate.

Question 5

Metal ion catalysis

Answer 5

Metal ions can participate in catalysis in several ways:

• Mediating oxidation reduction reactions
• Properly orienting the substrate in the enzyme active site through ionic interactions
• Stabilizing a negatively charged intermediate

Question 6

Catalytic power

Answer 6

Catalytic power is the ratio of the catalyzed reaction rate constant, 𝑘_cat, to the uncatalyzed reaction rate reaction constant, 𝑘_uncat

Question 7

Site-directed mutagenesis

Answer 7

Method used to determine which amino acid residues are critical to catalytic activity