Quantum mechanical (QM) cluster models are used to probe effects on the catalytic properties of protein phosphatase 1 (PP1) and alkaline phosphatase (AP) due to metal ions and active site residues. The calculations suggest that the phosphoryl transfer transition states in PP1 are synchronous in nature with a significant degree of P-O-lg cleavage, while those in AP are tighter with a modest degree of P-O-lg cleavage and a range of P-O-nuc formation. Similar to observations made in our recent work, a significant degree of cross talk between the forming and breaking P-O bonds complicates the interpretation of the Bronsted relation, especially in regard to AP for which the computed beta(lg)/beta(EQ,lg) value does not correlate with the degree of P-O-lg cleavage regardless of the metal ions in the active site. By comparison, the correlation between beta(lg)/beta(EQ,lg )and the P-O-lg bond order is more applicable to PP1, which generally exhibits less variation in the transition state than AP. Results for computational models with swapped metal ions between PP1 and AP suggest that the metal ions modulate both the nature of the transition state and the degrees of sensitivity of the transition state to the leaving group. In the reactant state, the degree of the scissile bond polarization is also different in the two enzymes, although this difference appears to be largely determined by the active site residues rather than the metal ions. Therefore, both the identity of the metal ion and the positioning of polar or charged residues in the active site contribute to the distinct catalytic characteristics of these enzymes. Several discrepancies observed between the QM cluster results and the available experimental data highlight the need for further QM/MM method developments for the quantitative analysis of metalloenzymes that contain open-shell transition metal ions.