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A proposed mechanism for metal-ion dependent polymerase reaction. The B-site metal ion is stably associated with the incoming dNTP and the enzyme. Binding of Mg2+ at the A-site aligns the reactants, in particular the 3′-OH, and promotes its deprotonation, which is assisted by the dNTP and the transient water. After the reaction is initiated and before the products are released, a third metal ion replaces R61 to stabilize the reaction intermediates.
