Fig. 5. A 3–methyladenine substrate modeled in AlkA's active site. 3–methyladenine (pink) was superimposed on the 1–azaribose moiety in the crystal structure of the AlkA–DNA complex. In the resulting model, the 3–methyladenine base stacks face-to-face against Trp272 and makes edge-on contacts with Tyr222. The open architecture of AlkA's substrate-binding pocket would accommodate many types of modified bases. Trp218 is located behind the ribose of the flipped out nucleotide, leaving no room for a water nucleophile (cf. Figure 6).