A, methylation reactions catalyzed by PRMTs. Type I and type II PRMTs make MMA. Type I PRMTs may then go on to make ADMA, while type II PRMTs produce SDMA. The second molecules of AdoMet and AdoHcy have been omitted for clarity. B, sequence alignment for rat PRMT1, rat PRMT3, rat PRMT4, yeast RMT1/Hmt1, and rat PRMT6. The conserved methionine pair is highlighted in dark red in light gray boxes. C, rat PRMT1-AdoHcy-peptide substrate complex shows the positioning of two strictly conserved methionine residues. The active site of rat PRMT1 (Protein Data Bank code 1OR8) is shown with AdoHcy in light orange (sulfur in dark orange), methionines 155 (left) and 48 (right) in dark red, and the substrate arginine group of the R3 peptide (ac-GGRGGFGGRGGFGGRGGFGG) in blue (terminal guanidino nitrogens are shown in dark blue).