An enzyme-catalyzed reaction. Shown here is the key step in the formation of a new phosphodiester bond in the active site of a DNA or RNA polymerase. The end of a growing chain of nucleic acid (the primer chain) is at the top left, and an incoming (deoxy)nucleoside triphosphate is at the lower left. The reaction begins with general base catalysis by an active-site residue (B) that abstracts a proton (H_a) from the attacking 3′ hydroxyl at the end of the primer chain. The oxygen of the hydroxyl group concurrently attacks the phosphorus of the a-phosphoryl group of the nucleoside triphosphate, displacing pyrophosphate (PP_i). The pyrophosphate is protonated by another active-site residue (usually a Lys, shown here as A), an example of general acid catalysis, which facilitates ejection of the PP_i. Two metal ions, usually two Mg²⁺, are in the active site. One metal ion lowers the pK_a of the primer 3′ hydroxyl to facilitate the general base catalysis. The other metal ion coordinates with and orients oxygens of the triphosphate and also aids catalysis by stabilizing the transition state of the reaction.