Chiral discrimination in the active site of ligases The ligases are enzymes that catalyze a synthesis process (the joining of two molecules) with concomitant hydrolysis of the diphosphate bond in a triphosphate or ATP. This class of enzymes is also termed synthases, carboxylase, or synthetases. The ligases can be very speci†c in the chirality of the substrate. For example, aminoacyl-tRNA synthetase (aaRS) is a ligase that catalyzes the esteri†cation of a speci†c amino acid and its cognate tRNA to form an aminoacyl-tRNA, leading to the charging of tRNA. The charging step is an essential prerequisite for protein synthesis, which depends on the chirality of the amino acid involved. The chance of misincorporation of wrong chirality is insigni†cant. Subsequently, a ribosome can transfer the correct amino acid from the tRNA onto a growing peptide chain, according to the genetic code, once the tRNA is charged with high †delity. Chiral discrimination is rather stringent as developed by evolution. Similar to the different aaRS, other ligases show remarkable speci†city in regard to the chirality of the substrate.