Alkaline phosphatase transition state stabilization

The AP from E. coli contains two Zn2+ ions and one Mg2+ ion in the active site.68,91 The Zn ions play the most direct roles in catalysis the Mg2+ has been suggested to function as the provider of the general base that deprotonates the Ser nucleophile, in the form of a Mg-coordinated hydroxide.98 All known alkaline phosphatases have this conserved three metal ion center, as well as an arginine residue (Arg-166 in E. coli AP) that plays a role in binding and probably in transition state stabilization (Fig. 18). 

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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