Figure 5. Crystal structures of duplex RNA containing base pairs involving adenine or N⁶‐methyladenine.

In each case, the relevant base pair is shown with its 2F_O‐F_C map contoured at 1.2σ. The sequences of each self‐complementary duplex are shown, with the relevant base pair highlighted in green, and N⁶‐methyl modification in red. 5‐Bromocytosine nucleotides are shown blue; each structure was solved by SAD using the anomalous scatter from the two bromine atoms, except for 5LR3 that was determined by soaking with CuCl₂.

• A
  A duplex containing a N⁶‐methyladenine‐uracil base pair (PDB 5LR5). Crystals of space group P6₅ were obtained that diffracted to 2.27 Å. A standard cis Watson–Crick base pair is formed in this duplex, despite the presence of the N⁶‐methyl group.
• B, C
  Accommodation of N⁶‐methyladenine in a cis Watson–Crick G·A base pair. Two duplex species were constructed containing adjacent G·A base pairs flanked by G‐C base pairs, with (B, PDB 5LQO) and without (C, PDB 5LQT) N⁶‐methyladenine at 1.87 and 1.50‐Å resolution, respectively. In both structures, the G·A base pairs are cis Watson–Crick pairs connected by two hydrogen bonds. Thus, N⁶‐methylation of adenine does not lead to disruption of these Watson–Crick G·A pairs.
• D, E
  Disruption of a trans sugar‐Hoogsteen G·A base pair by N⁶‐methyladenine. Crystal structures of RNA duplexes in which guanine opposes adenine or N⁶‐methyladenine with flanking G·U base pairs. In the absence of the N⁶‐methyl group (D, PDB 5LR3 at 1.65‐Å resolution), a trans Hoogsteen‐sugar G·A base pair is formed. In marked contrast, the N⁶‐methyladenine does not form a base pair with the guanine (E, PDB 5LR4 at 1.72‐Å resolution), and there is no hydrogen bonding between the two nucleobases. Thus, N⁶‐methylation of adenine prevents the formation of the trans Hoogsteen‐sugar G·A base pair.