Transfer RNA-mediated editing in threonyl-tRNA synthetase: The class II solution to the double discrimination problem

Threonyl-tRNA synthetase, a class II synthetase, uses a unique zinc ion to discriminate against the isosteric valine at the activation step. The cryst al structure of the enzyme with an analog of seryl adenylate shows that the noncognate serine cannot be fully discriminated at that step. We show that hydrolysis of the incorrectly formed ser-tRNA(Thr) is performed at a speci fic site in the N-terminal domain of the enzyme. The present study suggests that both classes of synthetases use effectively the ability of the CCA en d of tRNA to switch between a hairpin and a helical conformation for aminoa cylation and editing. As a consequence, the editing mechanism of both class es of synthetases can be described as mirror images, as already seen for tR NA binding and amino acid activation.