EVB and PTPase reaction

In the second part of the reaction the leaving group is replaced by a water molecule which hydrolyzes the phosphoenzyme via a second penta-coordinated structure The nucleophilic addition is modeled to occur concertedly 

For the first reaction step we also examine the most plausible pathway for an unprotonated mechanism (T 2- P3- P4, with total charge -3 on the reacting fragments). In this case there is no proton transfer between the nucleophile and the phosphate group and the negatively charged cysteine reacts directly with the phosphorus atom of the dianionic substrate. 

The EVB hamiltonians for the different phosphoryl transfer reactions were calibrated against relevant solution reactions utilizing experimental energetics data as well as semi-empirical and ab initio geometry optimizations (se below). As described elsewhere [18-20] the EVB calibration involves determining gas-phase energy differences - a as well as off-diagonal matrix elements 

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