Biochemistry—Shared Features of Protease Classes Which common mechanistic features are shared by serine proteases and aspartate (aspartyl) proteases?
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ABoth require water to complete the catalytic cycle
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BBoth use a basic residue to activate the nucleophile
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CBoth display specificity for certain amino acid sequences adjacent to the cleavage site
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DAll of the above
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ENone of the above
Answer
Correct Answer: All of the above
Explanation
Introduction / Context:Protease families achieve peptide bond hydrolysis using different active-site chemistries, yet they share several mechanistic themes. Recognizing these shared features aids in understanding catalysis, substrate recognition, and inhibitor design across protease classes.
Given Data / Assumptions:
- Serine proteases use a Ser-His-Asp triad and form a transient acyl-enzyme intermediate; water is required for deacylation.
- Aspartate proteases (e.g., pepsin family, HIV protease) use two Asp residues to activate a water molecule for direct nucleophilic attack.
- Both enzyme classes recognize specific sequence contexts around the scissile bond (S1, S1′, etc.).
Concept / Approach:Check each statement for validity across both families. Water involvement is universal for hydrolysis; base-assisted activation of the nucleophile occurs via His (serine proteases) or via Asp residues that polarize and deprotonate water (aspartate proteases). Sequence specificity arises from substrate-binding pockets that accommodate side chains selectively.
Step-by-Step Solution:
Step 1: Confirm water usage. Serine proteases require water to hydrolyze the acyl-enzyme, and aspartate proteases use water as the nucleophile.Step 2: Confirm base activation. Histidine acts as a base for serine proteases; a pair of aspartates activates water in aspartate proteases.Step 3: Confirm specificity. Binding pockets select residues, conferring sequence preferences for both families.Verification / Alternative check:Active-site structures and kinetic isotope effects support base-assisted proton transfers in both classes; substrate profiling defines sequence preferences.
Why Other Options Are Wrong:
- Each of A–C is correct; therefore D is correct and E is incorrect.
Common Pitfalls:Assuming that only serine proteases use a base or that only one class shows sequence specificity; ignoring the different identities of the base (His vs Asp pair).
Final Answer:All of the above