Thymidylate synthase structures. (A) Classical Thymidylate Synthase (TSase) is a homodimer with two identical active sites each binding dUMP and CH2H4folate. (B) Flavin-Dependent Thymidylate Synthase (FDTS) is a homotetramer with four identical active sites each binding dUMP, CH2H4folate, and FAD with possible allosteric sites for CH2H4folate. Each subunit is colored differently and ligand coloring is as follows: His53 (green), folate (yellow), FAD (cyan), and dUMP (magenta). PDB codes are 2KCE (TSase) and 4GT9 (FDTS).