Methyltransferases have emerged as valuable therapeutic targets in cancer and other pathologies. This enzyme class includes protein and RNA methyltransferases that establish methylation events on lysine and arginine or nucleotide bases, respectively. Protein methyltransferases fall into two distinct families, lysine methyltransferases (KMTs) and arginine methyltransferases (PRMTs). Many enzymes exhibit low turnover as recombinant proteins for in vitro biochemical analysis requiring highly sensitive assay formats such as radioactivity for measuring activity and characterizing inhibitors.