Figure 3: Simulated binding mode of m6A and hm6A in FTO after 10 ns of MD simulations.
From: FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA
(a) Binding model of FTO-m6A. (b) Binding model of FTO-hm6A. m6A and hm6A is highlighted in dashed blue and red circles. (c) Binding model comparison of m6A overlay with m3T. (d) Binding model comparison of hm6A overlay with m3T. Positions of the targeting methyl in m6A and hm6A are highlighted in dashed blue and red circles, respectively; the targeting methyl in m3T is highlighted in dashed magenta circles. Protein structure is shown in cartoon and active-site residues in sticks. Left panels use the m3T coordinate as in the FTO crystal structure (PDB ID: 3LFM) to prepare the initial location of the base in the FTO simulation through the following steps: fix the sugar ring position in 3LFM and mutate m3T to m3C, m6A, and hm6A, respectively. Right panels use the base coordinates from aligned AlkB crystal structures (PDB ID: 3O1P for εA, and 3O1O for m3T): align FTO and AlkB, take the aligned positions of m3T and εA as the starting point and mutate εA to m6A and hm6A, respectively.
