Crystal structure of the RNA demethylase ALKBH5 from zebrafish. Issue 6 (20th February 2014)

• Record Type: Journal Article
• Authors: Chen, Weizhong; Zhang, Liang; Zheng, Guanqun; Fu, Ye; Ji, Quanjiang; Liu, Fange; Chen, Hao; He, Chuan
• Is Part Of: FEBS letters. Volume 588:Issue 6(2014)
• Page Start: 892
• Page End: 898
• Publication Date: 2014-02-20
• Subjects: m6A -- N6-methyladenosine -- hm6A -- N6-hydroxymethyladenosine -- fm6A -- N6-formyladenosine -- A -- adenosine -- fALKBH5 -- zebrafish ALKBH5 -- α-KG -- α-ketoglutarate -- m1A -- 1-methyladenine -- m3C -- 3-methylcytosine -- ss -- single-stranded -- ds -- double-stranded -- cm5U -- 5-carboxy-methyluridine -- (S)-mchm5U -- (S)-5-methoxycarbonyl-hydroxymethyluridine -- m3T -- 3-methylthymine -- m3U -- 3-methyluracil -- ΔfALKBH5 -- truncated zebrafish ALKBH5 -- IPTG -- isopropyl β-D-1-thiogalactopyranoside -- SIN -- succinate acid -- hALKBH3 -- human ALKBH3 -- hALKBH8 -- human ALKBH8 -- hALKBH2 -- human ALKBH2 -- rmsd -- root-mean-square deviation -- ALKBH5 -- Crystal structure -- Demethylation -- N6-Hydroxymethyladenosine; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2014.02.021
• Languages: English
• ISSNs: 0014-5793

Abstract

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 1.65 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 m 6 A RNA demethylases, ALKBH5 and FTO, which may result in their slightly different pathways of m 6 A demethylation. Abstract : The crystal structure of ALKBH5 from zebrafish. fALKBH5 is comprised of a conserved jelly‐roll motif. fALKBH5 possesses a loop discriminating against duplex nucleic acids. Several active site residues are different between fALKBH5 and FTO. The structure may help understand the RNA demethylation mechanism.