Thus, it cannot explain why many enzymes do act on larger substrates, while
they are inactive on smaller counterparts. Given Fischer’s rationale, small substrates should be transformed at even higher rates than larger substrates since the
access to the active site would be easier. Furthermore, the hypothesis cannot explain
why many enzymes are able to convert not only their natural substrates but also
numerous nonnatural compounds possessing different structural features. Consequently, a more sophisticated model had to be developed.
Induced-Fit Mechanism
This rationale, which takes into account that enzymes are not entirely rigid but
rather represent delicate and soft structures, was developed by Koshland Jr. in the
1960s [117, 118].
16 It comprises that upon approach of a substrate during the
formation of the enzyme-substrate complex, the enzyme can change its conformation under the influence of the substrate structure so as to wrap itself around its
guest (Fig. 1.3). This phenomenon was denoted as the ‘induced fit’, which can be
illustrated by the interaction of a hand (the substrate) and a glove (the enzyme). This
advanced model can indeed explain why several structural features on a substrate
are required in addition to the reactive group. These structural features may be
located at quite a distance from the actual site of the reaction. The most typical
‘induced-fit’ enzymes are the lipases. They can convert an amazingly large variety
of artificial substrates which possess structures which do not have much in common
with the natural substrates – triglycerides.
A schematic representation of the ‘induced-fit’ mechanism is given in Fig. 1.3:
Whereas A represents the reactive group of the substrate, X depicts the complementary reactive group(s) of the enzyme – the ‘chemical operator’. Substrate part B
forces the enzyme to adapt a different (active) conformation,
17 where the ‘active’
groups X of the enzyme are correctly positioned to effect catalysis. If part B is
missing, no conformational change (‘induced fit’) takes place and thus the chemical
operators stay in their inactive state.
Enzyme
Substrate
Substrate
Enzyme
Fig. 1.2 Schematic representation of the ‘lock-and-key’ mechanism
16 ‘A precise orientation of catalytic groups is required for enzyme action; the substrate may cause
an appreciable change in the three-dimensional relationship of the amino acids at the active site,
and the changes in protein structure caused by a substrate will bring the catalytic groups into
proper orientation for reaction, whereas a non-substrate will not.’ See [117].
17 Conformational changes take place by hinge- and shear-type movements [119].
14
1 Introduction and Background Information
they are inactive on smaller counterparts. Given Fischer’s rationale, small substrates should be transformed at even higher rates than larger substrates since the
access to the active site would be easier. Furthermore, the hypothesis cannot explain
why many enzymes are able to convert not only their natural substrates but also
numerous nonnatural compounds possessing different structural features. Consequently, a more sophisticated model had to be developed.
Induced-Fit Mechanism
This rationale, which takes into account that enzymes are not entirely rigid but
rather represent delicate and soft structures, was developed by Koshland Jr. in the
1960s [117, 118].
16 It comprises that upon approach of a substrate during the
formation of the enzyme-substrate complex, the enzyme can change its conformation under the influence of the substrate structure so as to wrap itself around its
guest (Fig. 1.3). This phenomenon was denoted as the ‘induced fit’, which can be
illustrated by the interaction of a hand (the substrate) and a glove (the enzyme). This
advanced model can indeed explain why several structural features on a substrate
are required in addition to the reactive group. These structural features may be
located at quite a distance from the actual site of the reaction. The most typical
‘induced-fit’ enzymes are the lipases. They can convert an amazingly large variety
of artificial substrates which possess structures which do not have much in common
with the natural substrates – triglycerides.
A schematic representation of the ‘induced-fit’ mechanism is given in Fig. 1.3:
Whereas A represents the reactive group of the substrate, X depicts the complementary reactive group(s) of the enzyme – the ‘chemical operator’. Substrate part B
forces the enzyme to adapt a different (active) conformation,
17 where the ‘active’
groups X of the enzyme are correctly positioned to effect catalysis. If part B is
missing, no conformational change (‘induced fit’) takes place and thus the chemical
operators stay in their inactive state.
Enzyme
Substrate
Substrate
Enzyme
Fig. 1.2 Schematic representation of the ‘lock-and-key’ mechanism
16 ‘A precise orientation of catalytic groups is required for enzyme action; the substrate may cause
an appreciable change in the three-dimensional relationship of the amino acids at the active site,
and the changes in protein structure caused by a substrate will bring the catalytic groups into
proper orientation for reaction, whereas a non-substrate will not.’ See [117].
17 Conformational changes take place by hinge- and shear-type movements [119].
14
1 Introduction and Background Information