Charged with meaning: the structure and mechanism of phosphoprotein phosphatases

The new structural data obtained for PP1 and calcineurin—A resolve many of the outstanding questions about the catalytic nature of the Ser/Thr phosphatases. These enzymes may now be firmly classed as two-metal ion phosphatases. These data also provide a model for understanding a variety of phosphatases that share the two-metal-ion binding signature motif found in the Ser/Thr phosphatases. These enzymes are clearly important in the control of a variety of cellular functions and in a number of cases are important targets for therapeutic intervention. The structural data obtained for PP1 and calcineurin—A should certainly facilitate efforts to understand, and design inhibitors of, these proteins and related phosphatases.