Catalysis By Induced Fit
The advantages of the induced fit mechanism arise due to the stabilizing effect of strong enzyme binding. There are two different mechanisms of substrate binding: uniform binding, which has strong substrate binding, and differential binding, which has strong transition state binding. The stabilizing effect of uniform binding increases both substrate and transition state binding affinity, while differential binding increases only transition state binding affinity. Both are used by enzymes and have been evolutionarily chosen to minimize the Ea of the reaction. Enzymes which are saturated, that is, have a high affinity substrate binding, require differential binding to reduce the Ea, whereas small substrate unbound enzymes may use either differential or uniform binding.
These effects have led to most proteins using the differential binding mechanism to reduce the Ea, so most proteins have high affinity of the enzyme to the transition state. Differential binding is carried out by the induced fit mechanism - the substrate first binds weakly, then the enzyme changes conformation increasing the affinity to the transition state and stabilizing it, so reducing the activation energy to reach it.
It is important to clarify, however, that the induced fit concept cannot be used to rationalize catalysis. That is, the chemical catalysis is defined as the reduction of Ea‡ (when the system is already in the ES‡) relative to Ea‡ in the uncatalyzed reaction in water (without the enzyme). The induced fit only suggests that the barrier is lower in the closed form of the enzyme but does not tell us what the reason for the barrier reduction is.
Induced fit may be beneficial to the fidelity of molecular recognition in the presence of competition and noise via the conformational proofreading mechanism .
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