Conserved fold and variable topology of the MTase domain, a) The linear organization of six classes of amino-MTases (α-ζ) postulated by Malone et al. , m5C MTases (the prevailing archetypal topology labeled as m5C, and the two minor classes as ζ and DRM2), and the minimal MTases lacking the discrete TRD. The AdoMet-binding region is shown as a blue arrow, the catalytic region is shown as a red arrow, conserved motifs are labeled accordingly b). The topology diagram: triangles represent β-strands, circles represent a- and 310-helices, connecting lines represent loops; the thick lines correspond to the loops on the catalytic face of the protein, which harbor residues involved in cofactor binding and catalysis and most likely in DNA-binding. Elements forming the AdoMet-binding pocket are colored blue; elements forming the target base-binding/catalytic pocket are colored red. Circled Roman numerals represent nine motifs, the key motifs I and IV are shown in bold and underlined. Orange arrows show the topological breakpoints (N/C for generation of N- and C-termini) and sites of TRD insertion characteristic for the individual classes of MTases. The elements characteristic for the β-class MTases are shown in magenta, the corresponding elements found in M.Mwo I (δ-class) and TVN1413 (ζ-class) are shown in green and cyan, respectively.