Entatic state hypothesis

The mechanism of action of lysozyme has been suggested to involve strain in the substrate as a result of binding to the protein.31 The protein requires that the substrate binds to the protein in a distorted state that is close to the transition state of the reaction. The energy for this distortion can arise from the substrate binding energy. This example differs from the entatic state hypothesis because this strain arises from substrate binding and is not a feature of the protein structure. However, the entatic state... 

The additional comment that the high aflSnity of metalloenzymes for their metals as "compared with the stability of chelates which use the same ligands, argues against a thermodynamically strained coordination is similarly not relevant and based upon a misinterpretation of the entatic site hypothesis. Entasis implies that the difference in energy between the ground state and transition state for the enzymatic reaction is reduced, not that the metal-enzyme complex is thermodynamically less stable, as was inferred. Indeed, there is no reason to suppose that the distorted environment of a metal ion in an enzyme as opposed to a simple metal complex leads necessarily to an increase in free energy. The studies of alkaline phosphatase just presented certainly seem consistent with the entatic state hypothesis. 

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