Figure 1.

Dot1 is a conserved class I SAM-dependent methylase. (A) Sequence alignment of the conserved catalytic core region of Dot1 across multiple species that include yeast (NP_010728), worm (NM_058569), fly (AE003675), mouse (BB678539), and human (NP_115871). Secondary structure elements are shown above the alignment. The dashed line indicates disordered regions. Invariant amino acids are shown in white letters against a gray background, while conserved residues are in bold. Amino acids conserved across all five species are in bold against a green background. Every 10 amino acids is marked by a plus sign. The conserved methyltransferase fold motifs—I, post I, II, and III—are labeled and boxed in red. (B) The crystal structure of the substrate-binding pocket of human DOT1L (Protein Data Bank [PDB] code 1NW3) demonstrates that it is more similar to that of rat PRMT1 (PDB code 1ORI), a class I arginine methyltransferase, than to the KMT hNSD1 (PDB code 3OOI).