Subtopic: Fundamentals of Biomolecules, enzyme kinetics
Question Statement:
Which one of the following amino acid residues will destabilize an a-helix when inserted
in the middle of the helix?
Options:
(A) Pro
(B) Val
(C) Ile
(D) Leu
Official Answer Key:
A
Step-by-Step Solution & Explanation
### **Official Solution & Concept Analysis (GATE BT 2019 Q.47)**
**1. Governing Concept**:
- **Topic**: Protein Structure & Alpha-Helix Destabilization
- In an ideal right-handed $\alpha$-helix:
- The peptide backbone is tightly packed with intra-helical hydrogen bonds between the carbonyl oxygen of residue $i$ and amide proton of residue $i + 4$.
- **Proline (Pro, P)** is known as an **$\alpha$-helix breaker / disruptor**:
1. Its secondary amino (imino) nitrogen is part of a rigid five-membered pyrrolidine ring, preventing the backbone dihedral angle $\phi$ from adopting the required $\approx -60^\circ$ helical conformation.
2. Its nitrogen lacks an amide hydrogen ($\text{N}-\text{H}$) when participating in a peptide bond, making it incapable of donating a hydrogen bond to stabilize the helical turn.
- **Glycine (Gly, G)** also disrupts helices due to high conformational flexibility.
**2. Option Analysis**:
- **Option (A) [Proline] is CORRECT**: The classical $\alpha$-helix breaker that introduces an obligatory kink and disrupts helical hydrogen bonding.
- **Option (B) [Alanine] is INCORRECT**: Has the highest $\alpha$-helix propensity among all 20 amino acids.
- **Option (C) [Leucine] is INCORRECT**: Strong $\alpha$-helix former.
- **Option (D) [Methionine] is INCORRECT**: Favorable $\alpha$-helix former.
**3. Final Answer**:
- **Correct Choice**: **A**
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