aminoacylAMP

AminoacylAMP, also known as aminoacyl-adenylate, is a high-energy acyl-adenylate intermediate that activates amino acids for attachment to transfer RNAs or carrier proteins in biosynthetic systems. In the canonical pathway of protein synthesis, aminoacyl-tRNA synthetases catalyze a two-step reaction: an amino acid reacts with ATP to form aminoacylAMP and pyrophosphate (PPi). The aminoacylAMP is then transferred to the 3'-hydroxyl group of the terminal adenosine of tRNA, producing aminoacyl-tRNA and releasing AMP. The hydrolysis of PPi helps drive the overall reaction forward in vivo. Fidelity during charging is aided by editing mechanisms within many synthetases to prevent misactivation of incorrect amino acids.

AminoacylAMP also appears in nonribosomal peptide synthesis, where adenylation (A) domains activate amino acids to aminoacylAMP before transfer to a thiolation domain (PCP or similar) for subsequent condensation and chain elongation. In these systems, aminoacylAMP serves as the activated carrier that enables specific amino acid incorporation into nonribosomal peptides.

Chemically, aminoacylAMP is the mixed anhydride formed between the carboxyl group of an amino acid and the phosphate of AMP. The intermediate is transient and highly reactive, facilitating efficient coupling in the subsequent transfer step. Understanding aminoacylAMP clarifies the energetics and specificity of amino acid activation across both ribosomal and nonribosomal protein- and peptide-synthesis pathways.