Literature DB >> 24561204

Crystal structure of the RNA demethylase ALKBH5 from zebrafish.

Weizhong Chen1, Liang Zhang2, Guanqun Zheng2, Ye Fu2, Quanjiang Ji2, Fange Liu2, Hao Chen3, Chuan He4.   

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.
Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Entities:  

Keywords:  ALKBH5; Crystal structure; Demethylation; N(6)-Hydroxymethyladenosine

Mesh:

Substances:

Year:  2014        PMID: 24561204      PMCID: PMC3982313          DOI: 10.1016/j.febslet.2014.02.021

Source DB:  PubMed          Journal:  FEBS Lett        ISSN: 0014-5793            Impact factor:   4.124


  33 in total

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Journal:  Mol Cell       Date:  2012-11-21       Impact factor: 17.970

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7.  Variation in FTO contributes to childhood obesity and severe adult obesity.

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Journal:  PLoS Genet       Date:  2007-07       Impact factor: 5.917

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  21 in total

Review 1.  Gene expression regulation mediated through reversible m⁶A RNA methylation.

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Journal:  Nat Rev Genet       Date:  2014-03-25       Impact factor: 53.242

Review 2.  Multi-substrate selectivity based on key loops and non-homologous domains: new insight into ALKBH family.

Authors:  Baofang Xu; Dongyang Liu; Zerong Wang; Ruixia Tian; Yongchun Zuo
Journal:  Cell Mol Life Sci       Date:  2020-07-08       Impact factor: 9.261

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Review 4.  Novel positioning from obesity to cancer: FTO, an m6A RNA demethylase, regulates tumour progression.

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5.  Complementary Steric Engineering at the Protein-Ligand Interface for Analogue-Sensitive TET Oxygenases.

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Review 7.  N6-Adenosine Methylation (m6A) RNA Modification: an Emerging Role in Cardiovascular Diseases.

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8.  Mechanisms of substrate recognition and N6-methyladenosine demethylation revealed by crystal structures of ALKBH5-RNA complexes.

Authors:  Simranjeet Kaur; Nok Yin Tam; Michael A McDonough; Christopher J Schofield; Wei Shen Aik
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9.  Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5.

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Journal:  Nucleic Acids Res       Date:  2014-12-01       Impact factor: 16.971

Review 10.  Structure and function of dioxygenases in histone demethylation and DNA/RNA demethylation.

Authors:  Cheng Dong; Heng Zhang; Chao Xu; Cheryl H Arrowsmith; Jinrong Min
Journal:  IUCrJ       Date:  2014-10-28       Impact factor: 4.769

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