Figure 4.

Crystal structure of the FTO/MA complex. (A) Overall structure of the complex of MA bound to FTO (PDB code 4QKN) is presented in cartoon. The C-terminal domain (CTD) of FTO is colored in light blue, the N-terminal domain (NTD) in gray, the inhibitor MA in cyan, Mn²⁺ in orange, oxygen atom in red and nitrogen in blue. The part of the NRL consists of two antiparallel β-sheets: β3i and β4i. (B) The Fo-Fc OMIT density contoured to 2.5 sigma (left) and 2Fo-Fc density contoured to 1.0 sigma (right) confirm that MA is indeed bound. (C) Interaction networks between the FTO protein and MA inhibitor in the presence of cofactor and ion in the active pocket. The environmental residues involved in interactions are shown as sticks. Dark dotted lines indicate the coordination of Mn²⁺ by ligands and hydrogen bondings. (D) Superimposition of ALKBH5 (PDB code 4O7X) to CTD of FTO illustrates why MA cannot inhibit ALKBH5 demethylation. ALKBH5 is colored in magenta. The part of the NRL is indicated.