Zinc ion mediated amino acid discrimination by threonyl-tRNA synthetase

Accurate translation of the genetic code depends on the ability of aminoacy l-tRNA synthetases to distinguish between similar amino acids. In order to investigate the basis of amino acid recognition and to understand the role played by the zinc ion present in the active site of threonyl-tRNA syntheta se, we have determined the crystal structures of complexes of an active tru ncated form of the enzyme with a threonyl adenylate analog or threonine, Th e zinc ion is directly involved in threonine recognition, forming a pentaco ordinate intermediate with both the amino group and the side chain hydroxyl , Amino acid activation experiments reveal that the enzyme shows no activat ion of isosteric valine, and activates serine at a rate 1,000-fold less tha n that of cognate threonine. This study demonstrates that the zinc ion is n either strictly catalytic nor structural and suggests how the zinc ion ensu res that only amino acids that possess a hydroxyl group attached to the S-p osition are activated.