Crystal structure of the RNA demethylase ALKBH5 from zebrafish

被引：61
作者：
Chen, Weizhong [1 ,2 ,3 ,4 ,5 ]
Zhang, Liang [2 ,3 ]
Zheng, Guanqun [2 ,3 ]
Fu, Ye [2 ,3 ]
Ji, Quanjiang [2 ,3 ]
Liu, Fange [2 ,3 ]
Chen, Hao [4 ,5 ]
He, Chuan [2 ,3 ]
机构：
[1] Univ Sci & Technol China, Dept Chem Phys, Hefei 230026, Anhui, Peoples R China
[2] Univ Chicago, Dept Chem, Chicago, IL 60637 USA
[3] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA
[4] Nanjing Univ, Sch Chem & Chem Engn, Inst Coordinat Chem, Nanjing 210093, Jiangsu, Peoples R China
[5] Nanjing Univ, Sch Chem & Chem Engn, State Key Lab Coordinat Chem, Nanjing 210093, Jiangsu, Peoples R China
来源：
FEBS LETTERS | 2014年 / 588卷 / 06期
基金：
美国国家卫生研究院;
关键词：
ALKBH5; Crystal structure; Demethylation; N-6-Hydroxymethyladenosine; OXIDATIVE DEMETHYLATION; MESSENGER-RNA; FTO GENE; DNA; OBESITY; N6-METHYLADENOSINE; PURIFICATION; RECOGNITION; METHYLATION; NUCLEOSIDES;
D O I：
10.1016/j.febslet.2014.02.021
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 angstrom. 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. Structured summary of protein interactions: ALKBH5 and ALKBH5 bind by x-ray crystallography (View interaction) (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码：892 / 898
页数：7
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