title: Crystal structure of the RNA demethylase ALKBH5 from zebrafish.
abstract: ALKBH5, a member of AlkB family proteins, has been reported as a mammalian N(6)-methyladenosine (m(6)A) RNA demethylase. Here we report the crystal structure of zebrafish ALKBH5 (fALKBH5) with the resolution of 1.65Å. 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 m(6)A RNA demethylases, ALKBH5 and FTO, which may result in their slightly different pathways of m(6)A demethylation.
authors.affiliation: Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230026, China; Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA; Coordination Chemistry Institute and the State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Quanjiang
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA.
authors.forename: Fange
authors.initials: F
authors.lastname: Liu
authors.affiliation: Coordination Chemistry Institute and the State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA. Electronic address: chuanhe@uchicago.edu.
authors.forename: Chuan
authors.initials: C
authors.lastname: He
mesh_terms: D000071502:AlkB Homolog 5, RNA Demethylase; D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D056831:Coordination Complexes / Q000737:chemistry; D018360:Crystallography, X-Ray; D049308:Dioxygenases / Q000737:chemistry*; D006860:Hydrogen Bonding; D008345:Manganese / Q000737:chemistry; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D008565:Membrane Proteins; D029961:Zebrafish Proteins; D008345:Manganese; D049308:Dioxygenases; C559920:ALKBH5 protein, human; C588243:ALKBH5 protein, zebrafish; D000071502:AlkB Homolog 5, RNA Demethylase
keywords: ALKBH5; Crystal structure; Demethylation; N(6)-Hydroxymethyladenosine