Structure of the menin-MLL complex. (A) Sequence of the N-terminal fragment of MLL with MBM1 and MBM2 motifs. (B) Details of the menin-MBM1 interaction. Structure of the MBM1 is shown in stick representation (green carbon atoms) and MLL residues are labeled in blue. Menin is presented as a gray ribbon and selected side chains involved in contacts with MBM1 are shown as sticks (cyan carbon atoms); hydrogen bonds are shown as dashed lines. (C) The most significant contacts between MBM1 (green carbons) and selected menin side chains (cyan carbons). (D) Probing the MBM2-binding site on menin. MBM1 (shown in sticks) occupies a negatively charged central cavity on menin. The positions of D252 and L289 that were mutated to lysines are labeled. The electrostatic potential was calculated using APBS and mapped onto menin structure.⁴¹