Crystal structure of the RNA demethylase ALKBH5 from zebrafish |
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| Authors: | Weizhong Chen Liang Zhang Guanqun Zheng Ye Fu Quanjiang Ji Fange Liu Hao Chen Chuan He |
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| Affiliation: | 1. Department of Chemical Physics, University of Science and Technology of China, Hefei, Anhui 230026, China;2. Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, 929 E. 57th Street, Chicago, IL 60637, USA;3. Coordination Chemistry Institute and the State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China |
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| Abstract: | 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. |
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| Keywords: | 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 |
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