Crystal structure of the RNA demethylase ALKBH5 from zebrafish

ALKBH5, a member of AlkB family proteins, has been reported as a mammalian N6-methyladenosine (m6A) RNA demethylase. Here we report the crystal structure of zebrafish ALKBH5 (fALKBH5) with the resolution of 1.65 Å. Structural superimposition shows that fALKBH5 is comprised of a conserved jelly-roll motif. However, it possesses a loop that interferes potential binding of a duplex nucleic acid substrate, suggesting an important role in substrate selection. In addition, several active site residues are different between the two known m6A RNA demethylases, ALKBH5 and FTO, which may result in their slightly different pathways of m6A demethylation.