Figure 1

Computational analysis of the FTO family. Top. Multiple sequence alignment of the FTO family with known members of the non-heme dioxygenase superfamily. Red triangles above the alignment mark the conserved residues involved in iron and 2-oxoglutarate (2OG) binding with numbers indicating their position in AlkB. The numbers within the red box represent sequence insertions that we did not include in the alignment. X-Ray determined secondary structure of AlkB (PDB code 2fdi) [5] and hABH3 (PDB code 2iuw) [4] are shown below their sequences. PHD secondary structure prediction [26] for the FTO family is included below the human FTO sequence. The alignment was produced using a combination of T-COFFEE [17] and profile-to-profile alignment [24], using the structure-based superposition hABH3/AlkB alignment [28] as reference. Finally, the alignment was slightly refined manually. It was represented with the program Belvu [18] with a coloring scheme indicating average BLOSUM62 score (correlated to amino acid conservation) in each alignment column: dark red (greater than 3), violet (between 3 and 1) and light yellow (between 1 and 0.3). The sequences are named with their SwissProt or SpTrembl identifiers. Species abbreviations: Azovi, Azotobacter vinelandii; Caucr, Caulobacter crescentus; Comte, Comamonas testosteroni; Ecoli, Escherichia coli; Human, Homo sapiens; Jansp, Jannaschia sp.; Metfl, Methylobacillus flagellatus; Mouse, Mus musculus; Ocesp, Oceanospirillum sp.; Oryla, Oryzia latipes; Ostlu, Ostreococcus lucimarinus; Ostta, Ostreococcus tauri; Shewo, Shewanella woodyi; Synsp, Synechococcus sp.; Thaps, Thalassiosira pseudonana; Xenla, Xenopus laevis. Additional details about some lanes and FTO close homologous sequences can be found in Table 1. Complementary information, sequences, and alignments are accessible at [29]. Bottom. Structure of AlkB (PDB code 2fdi) indicating with sticks the invariant side chains in non-heme dioxygenases which are also conserved in the FTO family.