A missense mutation changes the codon CGU (arginine) to CGU (still arginine) in a region of a protein that is highly conserved and forms part of the active site. Discuss how this seemingly conservative change can still affect the protein’s tertiary structure and catalytic activity, considering hydrogen‑bonding, side‑chain interactions, and enzyme kinetics.

Step-by-step solution

1. Identify that both codons code for arginine, so the primary sequence is unchanged at that position.
2. Examine the side‑chain of arginine: a long, positively charged guanidinium group that forms specific hydrogen bonds and salt bridges.
3. A silent‑looking change may alter the codon usage, influencing co‑translational folding speed and ribosome pausing, which can modify how the arginine side‑chain is positioned.
4. If the new codon pairs with a different tRNA, the local folding kinetics may differ, potentially weakening or mis‑orienting hydrogen bonds with neighbouring residues.
5. Altered packing can change the geometry of the active‑site pocket, decreasing substrate affinity (higher K_m) or lowering turnover number (k_cat).
6. Summarize that despite unchanged amino‑acid identity, the mutation can impair tertiary structure and enzyme function.

Concept tested: Effect of missense mutation on protein function

Published 4 October 2026 · How this solution was prepared and checked