Fig. 1. Postulated Alkbh5 activation pathway.

(A) Postulated paths for formation of the catalytically competent oxyferryl species. (B) Close-up view of the active site from the crystal structure of Alkbh5 in complex with Mn²⁺ (orange sphere) and off-line αKG (cyan and red sticks) [Protein Data Bank (PDB) code: 4NRO]. The side chains forming the 2-His-1-carboxylate facial-triad are shown as sticks (carbon, nitrogen, and oxygen atoms are colored gray, blue, and red, respectively). The in-line αKG configuration (purple and red sticks) was modeled in the active site based on the x-ray structure of Alkbh2 in complex with the primary and secondary substrate (PDB code: 3RZJ). An m⁶A-containing oligonucleotide was modeled in the active site (orange, blue, and green cartoon) based on the x-ray structure of AlkB in complex with the primary and secondary substrate (PDB code: 4NID).