Interactions of Ser87 (purple) and Gln237 (gold) of the cytosine-5-methyltransferase from HhaI (M.HhaI) with the target cytosine base (red) and the orphan guanine base (green) during the initial stages of flipping of the target cytosine out of the DNA duplex and into that active site of M.HhaI. Left image shows the competition of Ser87 for the normal Watson-Crick basepair hydrogen bonds and the right image shows the stabilization of an early flipped state by Ser87 and Gln237. see Huang, N. Banavali, N.K., and MacKerell, Jr., A.D. Protein-facilitated base flipping in DNA by cytosine-5-methyltransferase, Proceedings of the National Academy of Sciences, USA, 2003, 100: 68-73

University of Maryland School of Pharmacy