In carbonic anhydrase II$,$ mutation of the proton$-$shuttle residue His $64$ to Ala was expected to result in a decrease in the maximal catalytic rate. However, in buffers such as imidazole with relatively small molecular components, no rate reduction was observed. In buffers with larger molecular components, significant rate reductions were observed.

Which statement correctly explains why there was no rate reduction in the imidazole buffer?

The $pH$ of the buffer containing large molecules rapidly increases during the reaction.

Large buffer molecules displace the essential zinc ion from carbonic anhydrase.

Small imidazole molecules reach the active site to compensate for the missing histidine.

High concentrations of imidazole revert the mutated alanine residue to a histidine.