Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

Enzymes are Wonderful Catalysts 45
His 289
H
N
H
N
N
O −
H 3 C
Cl
N
H
H
O
O
CH 3
Asp 124
O
Cl −
Asp 124
O
His 289
H
N
His 289
H
N +
N
CH 3
His 289
Asp 124
O
N
H
CH 3
O −
HO
HO
Asp 124
O
O
−
Figure 3.19 Mechanism for haloalkane dehalogenase.
3.7 The use of strain energy in enzyme catalysis
The concept of ‘strain’ is one that is rather diYcult to explain, since it occurs
very rarely in organic reactions, and there are only a few examples of enzymatic
reactions in which there is evidence that it operates. Remember that the overriding
factor in achieving rate acceleration in enzyme-catalysed reactions is the
diVerence in free energy between the ES complex and the transition state of the
enzymatic reaction. If the enzyme can somehow bind the substrate in a strained
conformation which is closer to the transition state than the ground state
conformation, then the diVerence in energy between the bound conformation
and the transition state will be reduced, and the reaction will be accelerated (see
Figure 3.20).
How can an enzyme bind its substrate in a strained conformation Is that
not energetically unfavourable The answer to these questions is that if the
substrate is of a reasonable size, the enzyme can form a number of enzyme–
substrate binding interactions, and the total enzyme–substrate binding energy
can be quite substantial. In some cases, in order to beneWt from the most
favourable overall binding interactions, the substrate must adopt an unfavourable
conformation in a part of the molecule. That part of the substrate may
cunningly happen to be where the reaction is going to take place! In thermodynamic
terms, the enzyme uses its favourable binding energy in the rest of the