Structural Flexibility Can Increase the Specificity of Enzymes

Although precise positioning of the reactants is a fundamental aspect of enzyme catalysis, most enzymes undergo some change in their structure when they bind substrates. A particularly dramatic example is hexokinase, which catalyzes the transfer of a phosphate group from adenosine triphosphate (ATP) to glucose. 

When hexokinase binds glucose, its structure changes in a way that brings together the elements of the active site (fig. 8.3). The enzyme literally closes like a set of jaws around the substrate Such a structural change is often referred to as an induced fit. 

Enfolding a substrate in this way can serve to maximize the favorable entropy change associated with removing a hydrophobic substrate molecule from water. It also allows the enzyme to control the electrostatic effects that promote formation of the transition state. The substrate is forced to respond to the directed electrostatic fields from the enzyme s functional groups, instead of the disordered fields from the solvent. 

Structural changes also contribute to the high specificity of some enzymatic reactions. In hexokinase, the structural change induced by glucose promotes the binding of the other substrate, ATP. ATP does not bind to the enzyme 

Hexokinase does not catalyze this side reaction it waits for glucose to bind first. 

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General-Base and General-Acid Catalysis Avoids the Need for Extremely High or Low pH Electrostatic Interactions Can Promote the Formation of the Transition State Enzymatic Functional Groups Provide Nucleophilic and Electrophilic Catalysis Structural Flexibility Can Increase the Specificity of Enzymes... 

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