Question

The irreversible inhibitor Iodoacetate binds with which group at the active site of the enzyme papain to make them inactive.

• A. Sulfhydryl group
• B. Hydroxyl group
• C. Methyl group
• D. Amino group

Hint:

Alkylating agents like iodoacetate and iodoacetamide are widely used in biochemistry to modify active-site cysteine residues.

Answer 1

The Correct Option is A

Step 1: Understanding the Concept:
Irreversible inhibitors bind to enzymes via stable covalent bonds, permanently altering the active site and abolishing enzymatic activity.
Papain is a plant-derived protease widely studied as a model for cysteine proteases.

Step 2: Detailed Explanation:
The catalytic mechanism of papain relies on a highly nucleophilic sulfhydryl group (\(\text{-SH}\)) belonging to a cysteine residue (Cys-25) located in its active site.
This active site sulfhydryl group forms a covalent acyl-enzyme intermediate during the cleavage of peptide bonds.
Iodoacetate (\(\text{ICH}_2\text{COO}^-\)) is a classic alkylating agent that targets reactive sulfhydryl groups.
When iodoacetate is introduced, the nucleophilic sulfur atom of Cys-25 attacks the methylene carbon of iodoacetate, displacing the iodide ion: \[ \text{Enz-CH}_2\text{-SH} + \text{ICH}_2\text{COO}^- \rightarrow \text{Enz-CH}_2\text{-S-CH}_2\text{COO}^- + \text{H}^+ + \text{I}^- \]
This reaction forms a stable, covalent carboxymethyl derivative (carboxymethylcysteine) at the active site.
This modification blocks substrate access and disables the nucleophilic capability of Cys-25, inactivating the enzyme.

Step 3: Final Answer:
Iodoacetate inactivates papain by binding covalently to the sulfhydryl group of its active-site cysteine residue.