A STRUCTURE-BASED MULTIPLE SEQUENCE ALIGNMENT OF ALL CLASS-I AMINOACYL-TRANSFER-RNA SYNTHETASES

The superimposable dinucleotide fold domains of MetRS, GlnRS and TyrRS define structurally equivalent amino acids which have been used to co nstrain the sequence alignments of the 10 class I aminoacyl-tRNA synth etases (aaRS). The conservation of those residues which have been show n to be critical in some aaRS enables to predict their location and fu nction in the other synthetases, particularly: i) a conserved negative ly-charged residue which binds the alpha-amino group of the amino acid substrate; ii) conserved residues within the inserted domain bridging the two halves of the dinucleotide-binding fold; and iii) conserved r esidues in the second half of the fold which bind the amino acid and A TP substrate. The alignments also indicate that the class I synthetase s may be partitioned into two subgroups: a) MetRS, IleRS, LeuRS, ValRS , CysRS and ArgRS; b) GlnRS, GluRS, TyrRS and TrpRS.