A tyrosine-to-histidine mutation in the active site of an enzyme significantly
affects its activity. The reaction is likely to be
Acid-catalysed
Base-catalysed
Free radical-catalysed
None of the above
A tyrosine-to-histidine mutation in an enzyme’s active site significantly reduces activity because the original enzyme likely relies on base-catalysed mechanisms, where tyrosine’s weaker basicity is optimal, but histidine’s stronger basicity (pKa ~6-7 vs. tyrosine’s ~10) disrupts proton transfer balance. The correct answer is base-catalysed.
Why Base-Catalysed?
Tyrosine (Tyr) acts as a general base by accepting protons with controlled strength due to its phenolic side chain, facilitating substrate activation in many hydrolases and transferases. Replacing it with histidine (His), which has an imidazole ring more eager to deprotonate at physiological pH, shifts equilibrium unfavorably—often making the site too basic, slowing catalysis or stabilizing wrong intermediates. This mutation exemplifies how active site pKa tuning is critical for base catalysis efficiency.
Acid-Catalysed Option Explained
In acid-catalysed reactions, residues like aspartate or glutamate donate protons; tyrosine can assist mildly but isn’t primary. A Tyr-to-His swap wouldn’t drastically impair this, as histidine’s conjugate acid (pKa ~6) remains a decent proton donor, unlike in base roles where excess basicity harms. Thus, activity loss points away from pure acid catalysis.
Free Radical-Catalysed Unlikely
Free radical mechanisms involve residues stabilizing unpaired electrons, like tyrosyl radicals in ribonucleotide reductase, but histidine rarely participates directly and lacks tyrosine’s radical stability from delocalized phenoxy electrons. Mutation effects here would stem from structural changes, not catalytic mode, so this doesn’t fit significant activity drops.
Why Not None?
The pronounced impact ties directly to acid-base properties, ruling out “none” since Tyr and His differ sharply in proton handling, a hallmark of general acid/base catalysis in enzymes.
