Enzyme steric repulsion

Transition-state stabilization in chymotrypsin also involves the side chains of the substrate. The side chain of the departing amine product forms stronger interactions with the enzyme upon formation of the tetrahedral intermediate. When the tetrahedral intermediate breaks down (Figure 16.24d and e), steric repulsion between the product amine group and the carbonyl group of the acyl-enzyme intermediate leads to departure of the amine product. 

The most probable interpretation of the above results is that the conformation disfavored by steric repulsion between the ortho- and a-substituents is the same conformation that is required for the substrate to be bound in the active site of the enzyme. Undoubtedly it is conformation A (syn-periplanarwith respect to the ortho- and a-substituents) illustrated in Fig. 9. If the substrate could undergo the reaction via the other planar conformation (B), the expected product would have been obtained, because conformation (B) is free from steric repulsion between the two substituents, and the substrate would have had no difficulty to take up this conformation. The actual inactivity of the two compounds (X, R = Cl, CH3 and CH3, CH3) suggests that, for some reason, conformation (B) is disfavored in the pocket of the enzyme. Then, how much is the energy... 

Although the prediction of the crystal structure from the theoretical calculation has not been solved yet, it seems possible to predict the reaction process from the crystal structure of reactant molecule, since the product molecule should be made suffering from steric repulsion in the crystaUine lattice of the reactant crystal. The term of reaction cavity was first proposed by Lee and Richards to interpret the reaction region within the enzyme molecule [15]. Cohen proposed a qualitative concept of the reaction cavity, as shown in Fig. 2.11 [16]. He proposed that since the reacting molecules occupy a space of a certain size and shape in the starting crystal, the reaction cavity is surrounded by the contact surface of the surrounding molecules. The topochemical principle can be interpreted to mean that those reactions which proceed under lattice control do so with minimum distortion of the surface of the reaction cavity. Therefore, the reaction of the route (a) is more favorable than that of (b). 

For modeling the essential features of the geometrically isolated environments in the active sites of enzymes, we designed the molecular bowls shown in Figure 11.3. The functional groups X and Y are isolated from each other by the steric repulsion between the peripheral moieties of the bowls. Their reactivity with other molecules is not inhibited so much because of the relatively large space around the central functionality. 

CNDO/2 Theoretical calculations have been used to predict the favoured conformations of creatine and creatine derivatives, including phosphocreatine. These calculations predict that phosphocreatine may adopt conformation (35) to avoid unnecessary steric and electrostatic repulsions.110 The possibility also exists that creatine kinase phosphorylates creatine stereospecifically to form the favoured conformation (35) at the active site of the enzyme. When chicks are fed a diet containing cyclocreatine (l-carboxymethyl-2-iminoimidazole), the phosphorylated... 

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