I read chapter 9 in the book Biochemistry (5th edition), by Berg, Tymoczko, and Stryer (provided in the NCBI site here). It describes the mechanism of action of the chymotrypsin enzyme. The catalysis is performed through the catalytic triad consisting of serine-195, histidine-57, and aspartate-102.
What intrigued me is the following section on the related enzyme subtilisin, which also has a catalytic triad but with different residue numbers:
9.1.5. The Catalytic Triad Has Been Dissected by Site-Directed Mutagenesis
[...] As expected, the conversion of active-site serine 221 into alanine dramatically reduced catalytic power. [...] The mutation of histidine 64 to alanine had very similar effects. [...]
These observations support the notion that the serine-histidine pair act together to generate a nucleophile of sufficient power to attack the carbonyl group of a peptide bond. The conversion of aspartate 32 into alanine had a smaller effect, although the value of $k_\mathrm{cat}$ still fell to less than 0.005% of its wild-type value.
My problem is in what it says next:
The simultaneously conversion of all three catalytic triad residues into alanine was no more deleterious than the conversion of serine or histidine alone. Despite the reduction in their catalytic power, the mutated enzymes still hydrolyze peptides a thousand times as rapidly as does buffer at pH 8.6.
A graph of the relative rates can be taken from this link:
My question is: how can it be that after replacing all the triad residues, the enzyme still possess such a great catalytic activity? What is the mechanism behind that phenomenon?
