Figure 4.

Crystal structure of the DNMT3B-3L–harmine complex reveals harmine binds at the SAM-binding pocket. (A) Overall crystal structure of the DNMT3B-3L–harmine complex: DNMT3B in green, DNMT3L in blue, and harmine represented by the orange spheres. Two harmine molecules are bound in the SAM-binding pockets of dimeric DNMT3B. Inset shows a close-up view of the interactions between harmine and DNMT3B. Green dotted lines indicate hydrogen bonds. (B) The cofactor SAM-binding pocket in the DNMT3B-3L–SAH complex (PDB code 6KDP). SAH is bound in the SAM-binding pocket. (C) Harmine binds at the SAM-binding pocket of the DNMT3B-3L–harmine complex (this study, PDB code 7X9D). Harmine is displayed as a stick model fitted in the 2F_o – F_c omit map (contoured at 1 σ). (D) 2D schematic depicting the interactions between DNMT3B and SAH in the crystal structure of the DNMT3B-3L–SAH complex. (E) 2D schematic depicting the interactions between DNMT3B and harmine in the crystal structure of the DNMT3B-3L–harmine complex. The interactions were generated by LigPlot⁺.⁴⁹ Residues linking SAH or harmine via hydrogen bonds are shown as green dashed lines. Residues that provide van der Waals interactions with SAH or harmine are labeled with red eyelash symbols.