Nucleotidyltransferases

Nucleotidyltransferases are a broad family of enzymes that catalyze the transfer of a nucleotidyl group from a nucleoside triphosphate to an acceptor substrate, most commonly forming a phosphodiester bond. This activity underlies the synthesis and processing of nucleic acids, as well as the maturation of RNA ends and various nucleotide-modification reactions.

Although diverse in substrate range, nucleotidyltransferases share a conserved core known as the nucleotidyltransferase (NTase) fold and typically use a two-metal-ion mechanism. Active-site residues coordinate divalent metal ions, activating a nucleophile on the acceptor and promoting departure of pyrophosphate. This family includes several distinct enzyme types that catalyze related chemistry but act on different acceptors.

Representative enzymes include DNA polymerases and DNA ligases, which fill in and seal DNA during replication and repair; poly(A) polymerases, which add polyadenylate tails to eukaryotic mRNA; tRNA nucleotidyltransferases, which add the CCA sequence to tRNA molecules; and terminal deoxynucleotidyl transferase, involved in generating diverse junctions during immune receptor diversification. Other members modify RNA or participate in RNA repair by adding nucleotidyl units to RNA ends or to damaged nucleotides.

NTases are pervasive across bacteria, archaea, and eukaryotes, reflecting an ancient and adaptable catalytic core. Through specialization, the family supports essential processes in genome maintenance, RNA metabolism, and cellular signaling, making nucleotidyltransferases a central theme in molecular biology.