Multiple sequence alignment of SAM synthetases. Essential amino acids for the first (*) and the second substrate binding subunit are numbered as in gi:46015497 (PDB structure 1P7L and 1RG9). Aligned sequences represent protein from Archaea (gi:3334428 – M. jannaschii), Eukaryota (gi:400245 – H. sapiens, gi:6016553 – C. elegans), and Bacteria (gi:46015497 – E. coli, gi:15836994 – X. fastidiosa, gi:22095828 – F. nucleatum, gi:13357974 – U. parvum, gi:2500686 – M. pneumoniae, gi:21646472 – C. tepidum). Residues are highlighted according to the amino acid properties with designations as in Figure 2. Substrate binding is annotated below the alignment as follows: small letters – water mediated interactions; inverted colors – interactions with ligand from the second subunit of the homodimeric protein ; A/a – adenosyl moiety; R – ribosyl moiety, M/m – methionine moiety; (+) – Mg2+; K – K+; P – PPNP/Phosphate moiety. Consensus positions of the secondary structure elements are shown above the alignment. Numbers in parentheses indicate number of residues omitted for clarity.