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. 2020 Sep 28;117(41):25284–25292. doi: 10.1073/pnas.2007349117

Fig. 3.

Fig. 3.

Structural analysis of FTO and ALKBH5 provides insight into m6A demethylation biochemistry. (A) Nucleobase recognition region of FTO:m6dA cocrystal structure (PDB ID code 5ZMD, purple). Key residues which facilitate understanding of the FTO m6A demethylation mechanism are in yellow sticks. (B) Superimposition of ALKBH5 (PDB ID code 4NRP, pale orange) with FTO:m6dA cocrystal structure, with FTO removed for clarity. Key residues which facilitate understanding of the unique m6A demethylation mechanism of ALKBH5 are in pink sticks. (C) A graphical illustration of the FTO nucleobase recognition region interacting with hm6A. An additional hydrogen bond with E234 should disfavor Schiff base formation and explains why hm6A is the major product of FTO. (D) A graphical illustration of how K132 and Y139 of ALKBH5 in the nucleobase recognition region facilitate formation of a covalent intermediate via elimination of water.