adenylyltransferases

Adenylyltransferases are enzymes that catalyze the transfer of an adenylyl group (AMP) from ATP to an acceptor substrate, producing an AMP-modified product and pyrophosphate. They belong to the broader family of nucleotidyltransferases and are found in bacteria, archaea, and eukaryotes. The reaction typically proceeds via direct transfer of the adenylyl moiety to a nucleophilic site on the acceptor, and the activity often depends on divalent metal ions such as Mg2+ or Mn2+.

Adenylyltransferases participate in a range of biological processes. In metabolism, the regulatory adenylylation of glutamine synthetase (GS) by the enzyme adenylyl transferase (GlnE) modulates GS activity in response to nitrogen status, providing reversible on/off control of nitrogen assimilation. In antibiotic resistance, aminoglycoside nucleotidyltransferases (ANTs) inactivate aminoglycoside antibiotics by transferring AMP to the antibiotic molecule, reducing drug efficacy. In signaling and protein regulation, a subset of AMP transferases catalyze post-translational adenylylation (AMPylation) of target proteins, altering activity or interactions; Fic domain-containing proteins are among the best-studied examples of such enzymes.

Structural diversity exists among adenylyltransferases, with active sites adapted to different substrates and reaction contexts. Despite this diversity, the unifying feature is the concerted transfer of an AMP moiety from ATP to a substrate, a reaction that integrates metabolism, regulation, and cellular defense mechanisms. The clinical and biotechnological relevance of adenylyltransferases stems from their roles in metabolic control and antibiotic resistance, as well as from their potential as targets for inhibitors or novel biotechnological tools.