Biochemistry—Comparing Protease Mechanisms Which statement is FALSE when comparing classical serine proteases with the HIV protease (an aspartyl protease)?

Introduction / Context:
Proteases employ diverse catalytic strategies to hydrolyze peptide bonds. Serine proteases and aspartyl proteases (such as HIV protease) represent two mechanistic archetypes. Recognizing what is shared and what is distinct is crucial for understanding inhibitor design and drug specificity.

Given Data / Assumptions:

• Serine proteases use a catalytic Ser-His-Asp triad and proceed via a covalent acyl-enzyme intermediate.
• Aspartyl proteases use two aspartates to activate a water molecule for direct attack; no covalent acyl intermediate with the enzyme is formed.
• Both enzyme classes require water for hydrolysis and exhibit sequence preferences.

Concept / Approach:
Identify the statement that incorrectly claims a shared mechanistic detail. The presence or absence of a covalent acyl-enzyme intermediate is the critical discriminator: present in serine proteases; absent in aspartyl proteases, which use general acid-base catalysis to activate water for direct nucleophilic attack on the peptide carbonyl.

Step-by-Step Solution:

Verification / Alternative check:
Mechanistic studies and inhibitor structures (e.g., transition-state mimics) for HIV protease show tetrahedral intermediates without enzyme-bound acyl covalent species.

Why Other Options Are Wrong:

• Nucleophilic attack and water requirement: both true in their respective mechanisms.
• Sequence specificity: both classes exhibit contextual preferences.
• Metal independence: neither class is a metallo-protease.

Common Pitfalls:
Assuming all proteases use identical covalent strategies; overlooking that many proteases are noncovalent hydrolases utilizing activated water.

Final Answer:
Both form a covalent acyl-enzyme intermediate during catalysis