While free MgATP shows tridentate coordination of Mg2+ by each of the three phosphates, enzyme-bound ATP generally coordinates metals at the beta- and gamma-phosphates and only occasionally at the alpha-phosphate. Enzyme-catalyzed reactions of ATP are in-line nucleophilic displacements at either the alpha-, beta-, or gamma-phosphorus atom, as dictated by the relative positions of the enzyme-bound substrates. The divalent cation activates the attacked phosphoryl group and/or the leaving group of ATP by charge neutralization, electron withdrawal, and by adjustment of the conformation of the polyphosphate chain. Some ATP reactions require an additional divalent cation at the active site to adjust the protein conformation and/or to interact with the other substrate.