LysRS2

Lysyl-tRNA synthetase 2 (LysRS2) is an enzyme that attaches lysine to its cognate tRNA, producing Lys-tRNA^Lys, a central step in translating genetic information into proteins. LysRS2 belongs to the class II family of aminoacyl-tRNA synthetases and is one of two unrelated LysRS families, the other being LysRS1. LysRS2 is the predominant form found in the majority of bacteria, archaea, and eukaryotes, while LysRS1 is present only in a minority of organisms.

Mechanism: The enzyme activates lysine by catalyzing its reaction with ATP to form lysyl-adenylate (Lys-AMP) and pyrophosphate (PPi). The Lys-AMP intermediate then transfers lysine to the 3'-OH of the tRNA^Lys, yielding Lys-tRNA^Lys and releasing AMP. The overall reaction uses one ATP and results in AMP and PPi. LysRS2 generally recognizes the identity elements of tRNA^Lys and exhibits specificity for this tRNA species, with some variation in recognition modes among different organisms.

Structure and evolution: LysRS2 is commonly a homodimer, with each subunit containing a catalytic core characteristic of class II aminoacyl-tRNA synthetases and an ancillary domain that can engage the tRNA, sometimes including an anticodon-binding region. The LysRS1 and LysRS2 families are not homologous, reflecting distinct evolutionary origins for lysyl-tRNA charging across life.

Biological role and significance: LysRS2 is essential for accurate decoding of the genetic code, enabling incorporation of lysine during protein synthesis. Because of its central role in translation and its presence in many pathogenic bacteria, LysRS2 is considered a potential target for antimicrobial strategies.