Structural Complementarity to Transition State

It is assumed that the active conformation of the enzyme matches the transition state of the reaction. This is supported by affinity studies which show that a compound with a structure analogous to the transition state of the reaction transition state analogs ) is bound better than the substrate. Hydroxamic acid, for example, is such a transition state analog which inhibits the reaction of triosephosphate isomerase (Fig. 2.13). Comparisons between the Michaelis constant and the inhibitor constant show that the inhibitor has a 30 times higher affinity to the active site than the substrate. 

The active site is complementary to the transition state of the reaction to be catalyzed. This assumption is supported by a reversion of the concept. It has been possible to produce catalytically active monoclonal antibodies directed against transition state analogs. The antibodies accelerate the reaction approximating the transition state of the analog. However, their catalytic activity is wetiker compared to enzymes because only the environment of the antibody which is complementary to the transistion state causes the acceleration of the reaction. 

Transition state analog inhibitors were used to show that in the binding the enzyme displaces the hydrate shell of the substrates. The reaction rate can be significantly increased by removing the hydrate shell between the participants. 

Other important factors in catalytic reactions are the distortion of bonds and shifting of charges. The substrate s bonds will be strongly polarized by the enzyme, and thus highly reactive, through 

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