Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

Enzymes are Wonderful Catalysts 41
Tyr 14
O
H
O
H
− O
O
Tyr 14
O −
H
O
H
O
O
Asp 38
Asp 38
Tyr 14
O
H
O
O
H
O −
Tyr 14
O −
H
O
O
H
O
Asp 38
Asp 38
Figure 3.15 Mechanism for ketosteroid isomerase.
Finally, enzymes which bind metal cofactors such as Zn 2þ and Mg 2þ can
utilise their properties as Lewis acids, i.e. electron pair acceptors. An example is
the enzyme thermolysin, whose mechanism is illustrated in Figure 3.16. In this
enzyme, Glu-143 acts as an active site base to deprotonate water for attack on
the amide carbonyl, which is at the same time polarised by co-ordination by an
active site Zn 2þ ion. The protonated glutamic acid probably then acts as an
acidic group for the protonation of the departing amine.
3.6 Nucleophilic catalysis in enzymatic reactions
Nucleophilic (or covalent) catalysis is a type of catalysis seen relatively rarely
in organic reactions, but which is used quite often by enzymes. It involves
nucleophilic attack of an active site group on the substrate, forming a covalent
bond between the enzyme and the substrate, and hence a covalent intermediate
in the reaction mechanism. This is a particularly eVective strategy for enzymecatalysed
reactions for two reasons. First, as we have seen before, an enzyme is
able to position an active site nucleophile in close proximity and correctly
aligned to attack its substrate, generating a very high eVective concentration
of nucleophile.