Lysyladenylate

Lysyladenylate, also called lysyl-AMP, is an activated intermediate in the enzymatic charging of transfer RNA with lysine. In organisms across domains, the amino acid lysine is first activated by ATP in a reaction catalyzed by lysyl-tRNA synthetase (LysRS). The carboxyl group of L-lysine forms a mixed anhydride with the 5'-phosphate of AMP, yielding lysyl-AMP and pyrophosphate (PPi). This transient acyl-adenylate is then used by LysRS to transfer the lysine residue to the 3'-terminal adenosine of tRNA^Lys, producing lysyl-tRNA^Lys and releasing AMP. The overall process is part of the aminoacylation or charging reaction that links amino acids to their cognate tRNAs, enabling accurate translation of the genetic code.

Chemically, lysyladenylate is characterized as an aminoacyl-adenylate: the lysine carboxyl group is activated as an acyl-adenylate, a high-energy intermediate that couples amino acid activation to tRNA transfer. In laboratory studies, lysyladenylate is typically too reactive to isolate under physiological conditions, and researchers often study analogs or use rapid-quench methods to capture aspects of its formation and transfer.

Role and relevance: Lysyladenylate is essential for accurate incorporation of lysine into proteins and is representative of the canonical two-step mechanism used by aminoacyl-tRNA synthetases across different amino acids. Disruption of lysyl-AMP formation or transfer can impair protein synthesis and cell viability.