Catalysis of the hydrolysis of phosphorylated pyridines by Mg(OH)+: a possible model for enzymatic phosphoryl transfer

The second-order rate constants for reaction of the Mg2+ complexes of phosphorylated pyridine monoanions with Mg(OH)+ are 10(4)-10(6)-fold larger than the second-order rate constants for their reaction with water (25 degrees C, ionic strength 1.5). Of the 10(6)-fold rate enhancement with the phosphorylated 4-morpholinopyridine/Mg2 complex, approximately 10(4)-fold is attributed to the greater nucleophilicity of Mg(OH)+ compared with water. The remaining catalysis of approximately 10(2)-fold is attributed to induced intramolecularity from positioning of the hydroxide ion and phosphoryl group by the Mg2+ ions. This reaction may provide a model for the role of a metal ion in increasing the concentration of the anions of enolpyruvate and serine and holding the nucleophile in the correct position for phosphoryl transfer in the reactions catalyzed by pyruvate kinase and alkaline phosphatase, for example. Some mechanisms that can provide catalysis of phosphoryl transfer through a metaphosphate-like transition state are reviewed briefly.