Structural comparisons of animal, protist, and viral CMTrs. (A) Schematic depiction of the Rossmann-like fold. (B) Structure-based multiple alignment of the sequence context surrounding the four key catalytic residues (yellow). The consensus for animal and viral CMTrs is shown on top and bottom, respectively. (C) Three-dimensional similarity of modeled CMTr structures determined by the DALI server depicting the structural similarity dendrogram on top and “all against all” multiple comparison at the bottom with orthologous proteins framed in black. Human Mettl3 (red star) was used as an outgroup indicating no similarity by near zero z-score (gray). (D,E) Three-dimensional structural alignment of CMTr1 (D) and CMTr2 (E) from humans (red), Drosophila (gray) and C. elegans (blue). The black star denotes the position of α 11 helix which is absent in C. elegans. The position of the cap analog (light blue) and the SAM (yellow) were inserted by superimposition from the published structure (PDB 4n48). (F) Three-dimensional structural alignment of CMTrs from vaccinia (red), SARS-CoV-2 (gray), and Zika virus (blue). The position of the cap analog (light blue) and the SAM (yellow) were inserted by superimposition from the published structure (PDB 1av6).
