Seryl-tRNA class IIa synthetases serylate cognate tRNASer in a highly specific two-step reaction. Because of the size and poor preservation of the serine codon sequence, long variable arm tRNASer takes up the role of the main identity elements from the otherwise common anticodon. The extra arm conditions specific enzyme-substrate recognition through interactions with the conserved helical arm of SerRS. Helical arm is a flexible N-terminal 60 Å long coiled-coil, which locks itself between TΨC and the long extra arm into what is called a protein sandwich, while making a hinge movement in respect to the catalytic domain. It only does so once the tRNA is bound across the synthetase dimer, which seems to be another specificity of the tRNASer-SerRS system. At the same time, motif 2 loop, which experiences conformational changes itself, helps in properly positioning the acceptor stem in the active site. Catalytic domain is a 7- or 8-stranded antiparallel β-sheet. The system just described is a typical bacterial tRNASer/SerRS system, very similar to archeal/eukaryal and mitohondrial, but substantially different from the methanogenic system. Besides the differences in the design and chemistry of the active site (catalytic zinc), methanogenic SerRSs differ in having two structural insertions in the catalytic domain – HTH (increases the dimer interface) and “serine ordering loop”. In spite of a completely different structural oraganization of the N-terminal domain, it retains a common orientation in relation to the catalytic domain. Another system that deviates from the typical is the mitochondrial one – in fact, mitochondrial synthetases compensate the loss of the mt tRNASer extra arm by acquiring new structural elements – the distal helix and the C-tail – which alongside certain helical arm regions lock the T-loop (a novel identity element) into an RNA-sandwich. Archeal/eukaryal system, in adition its typical helical domain, contains an archea-specific insertion, which collaborates with the core domain in forming a basic channel leading to the active site. It should be mentioned that the “pure” eukaryal system resembles greatly the bacterial, with slight insertial changes to the enzyme’s C-terminus additionally stabilize the enzyme (similar to the methanogenic HTH motif).