Fig. 1.

The tertiary structures of the five classes of S-adenosyl-l-methionine (AdoMet)-dependent methyltransferases (MTases). In each case a representative tertiary structure (left) and topology diagram (right) is shown. (a) Class I: tertiary structures have been determined for >33 family members, most containing a seven-stranded β sheet flanked by α helices (enzyme:PDB code, M.HhaI:6MHT). (b) Class II: the reactivation domain of methionine synthase contains a series of long β strands and binds to AdoMet in a shallow groove on the surface of the domain (MetH:1MSK). (c) Class III: the bilobal structure of CbiF contains an AdoMet-binding site between the two αβα domains, and a groove in the N-terminal domain is proposed to be the active-site cleft (CbiF:1CBF). (d) Class IV: the SPOUT family of RNA MTases contains a novel knot structure (magenta) at the C terminus that contributes to the AdoHcy-binding site (YibK:1MXI). (Helices that are not conserved between family members are shown in pale pink in the topology diagram.) (e) Class V: the SET-domain containing histone-lysine N-MTase family is formed by the combination of three small β sheets. The AdoMet-binding site is formed on a shallow groove of the protein and the substrate active site is proximal to the C-terminal tail, which is also involved in a knot-like structure (Set7/9:1O9S). Figures were generated using PYMOL (http://www.pymol.org).