Fig. 4. Enzymatic mechanism of DNA methyltransferases (DNMTs).
Methylation of cytosine begins with the nucleophillic attack of position 6 by a thiolate nucleophile. The resulting electron rich region at position 5 is then at attacked by the methyl group of Sadenosylmethionine (SAM). The reaction then proceeds with the removal of the hydrogen at position 5 by a basic amino acid in the active site of DNMT. In the final step, the double bond is reformed in the pyrimidine ring, resulting in elimination of bond between position 6 and the DNMT.