An aminoacyl tRNA synthetase whose sequence fits into neither of the two known classes

Aminoacyl transfer RNA synthetases catalyse the first step of protein synth esis and establish the rules of the genetic code through the aminoacylation of tRNAs. There is a distinct synthetase for each of the 20 amino acids an d throughout evolution these enzymes have been divided into two classes of ten enzymes each(1,2). These classes are defined by the distinct architectu res of their active sites, which are associated with specific and universal sequence motifs(1-5). Because the synthesis of aminoacyl-tRNAs containing each of the twenty amino acids is a universally conserved, essential reacti on, the absence of a recognizable gene for cysteinyl tRNA synthetase in the genomes of Archae such as Methanococcus jannaschii and Methanobacterium th ermoautotrophicum(6-8) has been difficult to interpret. Here we describe a different cysteinyl-tRNA synthetase from M. jannaschii and Deinococcus radi odurans and its characterization in vitro and in vivo. This protein lacks t he characteristic sequence motifs seen in the more than 700 known members o f the two canonical classes of tRNA synthetase and may be of ancient origin . The existence of this protein contrasts with proposals that aminoacylatio n with cysteine in M. jannaschii is an auxiliary function of a canonical pr olyl-tRNA synthetase(9,10).