It is possible that the substrate and enzyme interact unfavorably and this unfavorable interaction is relived in the transition state. We might think that the substrate is under stress meaning that it is subjected to forces but not distorted by them. It is more likely that the enzyme is strained, as for example in induced fit. Enzyme Mechanisms Induced fit Hexokinase catalyzes the ATP-dependent phosphorylation of glucose. An induced fit at an interface.
Lipases are enzymes that hydrolyze esters of long chain fatty acids.
The activation of the lipases at the interface is a result of a conformational change, induced fit, caused by the enzyme binding to the interface. Several residues in the protein participate in substrate binding. The binding of NAM4 in the chair conformation is unfavorable. Many glycosidases utilize a covalent intermediate in their mechanism. Here is a good example of transition state stabilization using a bacterial glycosidase .