Bacterial nucleotidyltransferases

Bacterial nucleotidyltransferases are a superfamily of enzymes that catalyze the transfer of nucleotidyl residues (e.g., AMP, GMP, CMP, or UMP) from donor molecules (such as nucleotide triphosphates) to acceptor substrates including sugars, nucleic acids, or metabolites[1][5][9]. Key examples include RmlA, which initiates the biosynthesis of rare NDP-sugars critical for cell wall and capsule formation, and tRNA nucleotidyltransferases that add the CCA tail to the 3′ end of tRNAs, a process essential for protein translation[1][9]. Other members like CD-NTase (cyclic dinucleotide transferase) participate in the synthesis of cyclic dinucleotides, important for bacterial innate immunity and antiviral defense[3]. Because many of these enzymes are essential for bacterial growth, survival, or virulence and have sufficient structural divergence from their human counterparts, they are attractive targets for antibiotic development[6][4]. Bacterial nucleotidyltransferases perform crucial biosynthetic and regulatory roles and are positioned as promising antibiotic targets, most notably due to their unique contributions to bacterial cell envelope structure, glycosylation, and specialized signaling pathways.

Other names

Nucleoside diphosphate sugar pyrophosphorylasetRNA nucleotidyltransferaseRNA nucleotidyltransferaseCCA-adding enzymeCD-NTase (cyclic dinucleotide transferase)LigT (tRNA ligase)

Enzyme inhibition: Small molecules may inhibit the catalytic or allosteric site to block the enzyme’s activity, suppressing synthesis of critical nucleotide or sugar metabolites required for bacterial survival[1][5][4]. Feedback inhibition: Natural rare NDP-sugars can allosterically regulate enzyme activity in feedback loops[5].