Proteases: Identify the enzyme that is NOT a cysteine active-site protease.

Introduction:
Proteases are classified by the catalytic residue/ion at the active site (e.g., serine, cysteine, aspartic, metalloproteases). This question probes recognition of protease classes by representative members.

Given Data / Assumptions:

• Calpain and papain are canonical cysteine proteases.
• Cathepsin D is a lysosomal aspartic protease.
• Caspases are cysteine proteases that cleave after aspartate residues.

Concept / Approach:
Identify which option belongs to a different catalytic class than the others by recalling hallmark families and cellular localization/functions.

Step-by-Step Solution:
1) Calpains: calcium-activated cysteine proteases involved in cytoskeletal remodeling.2) Papain: archetypal plant cysteine protease (papaya latex), classic model enzyme.3) Cathepsin D: lysosomal aspartic protease; uses two aspartates for acid-catalyzed hydrolysis.4) Caspase-3: cysteine protease, but with specificity for aspartate at P1; catalytic cysteine performs nucleophilic attack.

Verification / Alternative check:
Biochemical texts consistently classify cathepsin D among aspartyl proteases (not cysteine), confirming the outlier.

Why Other Options Are Wrong:

• (a) and (c) are true cysteine proteases.
• (d) Incorrect because not all listed enzymes are cysteine proteases.
• (e) Caspases are cysteine proteases despite the name suggesting aspartate involvement in substrate recognition.

Common Pitfalls:
Assuming “cathepsin” implies the same class across family members; conflating “aspartate specificity” (substrate) with “aspartic protease” (catalysis type).

Final Answer:
Cathepsin D (lysosomal aspartic protease)