Adenylyltransferase

Adenylyltransferase is an enzyme class that catalyzes the transfer of an adenylyl (AMP) group from ATP to a target substrate, producing an adenylylated product and pyrophosphate. This type of modification can alter the activity, stability, or interactions of the substrate protein or molecule, and it plays a role in regulating metabolism and signaling pathways.

In bacteria, the best-characterized example is glutamine synthetase adenylyltransferase, encoded by glnE. This bifunctional enzyme can both adenylylate and deadenylylate glutamine synthetase (GS), thereby toggling GS activity in response to nitrogen status. Adenylylation inactivates GS, while deadenylylation reactivates it. The activity of GlnE is regulated by PII signal transduction proteins (such as GlnB), whose modification state reflects cellular nitrogen availability.

Adenylyltransferases participate in a variety of other regulatory contexts as well. Some enzymes adenylylate regulatory proteins, metabolic enzymes, or ribonucleotides as part of adaptive responses to nutrients, redox changes, or stress. In many cases, the standard reaction is ATP-dependent: ATP + substrate → AMP-substrate + PPi, with magnesium or other divalent cations assisting catalysis. These enzymes often belong to the broader nucleotidyltransferase superfamily and share common catalytic features that enable transfer of the AMP moiety.

The term encompasses diverse enzymes across bacteria, archaea, and eukaryotes, with substrate specificity and regulatory control that vary by organism and pathway. In all cases, adenylyltransferase activity modulates the function of its target through reversible AMP modification in cellular regulation.