aminoacyladenylate

An aminoacyladenylate, commonly called aminoacyl-AMP, is a reactive intermediate formed during the aminoacylation of transfer RNA by aminoacyl-tRNA synthetases (aaRS). In the initial step of the charging reaction, an amino acid reacts with ATP in the enzyme’s active site to produce aminoacyl-AMP and inorganic pyrophosphate (PPi). The aminoacyl group remains activated in this adenylate form, enabling its transfer to RNA.

In a second step, the aminoacyl moiety is transferred from aminoacyl-AMP to the 3' hydroxyl group of the terminal adenosine (A76) of the tRNA, forming aminoacyl-tRNA and releasing AMP. This two-step mechanism activates the amino acid for attachment and ensures high fidelity in protein synthesis. The aminoacyl-AMP is a high-energy mixed anhydride and is typically stabilized transiently within the synthetase active site, with metal ions such as Mg2+ often playing a supporting role.

Different classes of aaRS employ distinct structural strategies to catalyze the same two-step process, but the formation and subsequent transfer of the aminoacyl-AMP is a unifying feature of tRNA charging. Fidelity mechanisms, including editing steps in some synthetases, help prevent mischarging of tRNA. While the aminoacyl-AMP itself is short-lived, it is a central intermediate that links amino acid activation to translation.