4o61 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
N6-Methyladenosine (m6A) is the most prevalent internal RNA modification in eukaryotes. ALKBH5 belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m6A in single stranded RNA. Here we report crystal structures of ALKBH5 in the presence of either its cofactors or the ALKBH5 inhibitor citrate. Catalytic assays demonstrate that the ALKBH5 catalytic domain can demethylate both ssRNA and ssDNA. We identify the tricarboxylic acid (TCA) cycle intermediate citrate as a modest inhibitor of ALKHB5 (IC50: ~488 muM). The structural analysis reveals that a loop region of ALKBH5 is immobilized by a disulfide bond which apparently excludes the binding of dsDNA to ALKBH5. We identify the m6A binding pocket of ALKBH5 and the key residues involved in m6A recognition using mutagenesis and ITC binding experiments.
Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single stranded m6A RNA demethylation.,Xu C, Liu K, Tempel W, Demetriades M, Aik W, Schofield CJ, Min J J Biol Chem. 2014 Apr 28. PMID:24778178[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑ Xu C, Liu K, Tempel W, Demetriades M, Aik W, Schofield CJ, Min J. Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single stranded m6A RNA demethylation. J Biol Chem. 2014 Apr 28. PMID:24778178 doi:http://dx.doi.org/10.1074/jbc.M114.550350
