National Center for
4NII: Crystal Structure Of Alkb D135i Mutant Protein With Cofactors Bound To Dsdna Containing M6a/a
Switching demethylation activities between AlkB family RNA/DNA demethylases through exchange of active-site residues
Angew. Chem. Int. Ed. Engl. (2014) 53 p.3659-3662
The AlkB family demethylases AlkB, FTO, and ALKBH5 recognize differentially methylated RNA/DNA substrates, which results in their distinct biological roles. Here we identify key active-site residues that contribute to their substrate specificity. Swapping such active-site residues between the demethylases leads to partially switched demethylation activities. Combined evidence from X-ray structures and enzyme kinetics suggests a role of the active-site residues in substrate recognition. Such a divergent active-site sequence may aid the design of selective inhibitors that can discriminate these homologue RNA/DNA demethylases.