Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

All Enzymes are Proteins 21
bonds between uncharged donors/acceptors are of energy 2.0–7.5 kJ mol
whilst hydrogen bonds between charged donors/acceptors are much
stronger, in the range 12.5– 25 kJ mol
1 .
(3) Non-polar (Van der Waals) interactions. Van der Waals interactions arise
from interatomic contacts between the substrate and the active site. Since
the shape of the active site is usually highly complementary to the shape of
the substrate, the sum of the enzyme–substrate Van der Waals interactions
can be quite substantial (50–100 kJ mol 1 ), even though each individual
interaction is quite weak (6–8 kJ mol
1 ). Since the strength of these interactions
varies with 1=r 6 they are only signiWcant at short range (2–4 Å), so a
very good ‘Wt’ of the substrate into the active site is required in order to
realise binding energy in this way.
(4) Hydrophobic interactions. If the substrate contains a hydrophobic group or
surface, then favourable binding interactions can be realised if this is bound
in a hydrophobic part of the enzyme active site. These hydrophobic interactions
can be visualised in terms of the tendency for hydrophobic organic
molecules to aggregate and extract into a non-polar solvent rather than
remain in aqueous solution. These processes of aggregation and extraction
are energetically favourable due to the maximisation of inter-water hydrogen-bonding
networks which are otherwise disrupted by the hydrophobic
molecule, as shown in Figure 2.19.
There are many examples of hydrophobic ‘pockets’ or surfaces in enzyme
active sites which interact favourably with hydrophobic groups or surfaces in
the substrate and hence exclude water from the two hydrophobic surfaces. As
mentioned above, these hydrophobic interactions may be very important for
1 ,
H
H
H O
H H
H
O
O
H
H H O
H
H
O
H H
O
O
H
H H
H
O
O H H
O
H
H
H O
H H
H
O
O
H
O
H
H H H O
H H
H O
O
H
H H
O
O
H
H H
H
O
O H H
O
H
H
Hydrophobic molecule in water
Figure 2.19 Hydrophobic interaction.
Additional water−water hydrogen
bonds possible if hydrophobic molecule
is excluded from water