Meclofenamic acid selectively inhibits FTO demethylation of m(6)A over   ALKBH5

doi:10.1093/nar/gku1276

CORC > 北京大学 > 化学与分子工程学院

	Meclofenamic acid selectively inhibits FTO demethylation of m(6)A over ALKBH5
	Huang, Yue ; Yan, Jingli ; Li, Qi ; Li, Jiafei ; Gong, Shouzhe ; Zhou, Hu ; Gan, Jianhua ; Jiang, Hualiang ; Jia, Gui-Fang ; Luo, Cheng ; Yang, Cai-Guang
刊名	核酸研究
	2015
关键词	PROMOTE PROTEIN STABILITY OBESITY-ASSOCIATED FTO OXIDATIVE DEMETHYLATION CRYSTAL-STRUCTURES RNA DEMETHYLASE ALKYLATION DAMAGE ESCHERICHIA-COLI MESSENGER-RNA HISTONE DEMETHYLASES MAXIMUM-LIKELIHOOD
DOI	10.1093/nar/gku1276
英文摘要	Two human demethylases, the fat mass and obesity-associated (FTO) enzyme and ALKBH5, oxidatively demethylate abundant N-6-methyladenosine (m(6)A) residues in mRNA. Achieving a method for selective inhibition of FTO over ALKBH5 remains a challenge, however. Here, we have identified meclofenamic acid (MA) as a highly selective inhibitor of FTO. MA is a non-steroidal, anti-inflammatory drug that mechanistic studies indicate competes with FTO binding for the m(6)A-containing nucleic acid. The structure of FTO/MA has revealed much about the inhibitory function of FTO. Our newfound understanding, revealed herein, of the part of the nucleotide recognition lid (NRL) in FTO, for example, has helped elucidate the principles behind the selectivity of FTO over ALKBH5. Treatment of HeLa cells with the ethyl ester form of MA (MA2) has led to elevated levels of m(6)A modification in mRNA. Our collective results highlight the development of functional probes of the FTO enzyme that will (i) enable future biological studies and (ii) pave the way for the rational design of potent and specific inhibitors of FTO for use in medicine.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000350207100037&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Biochemistry & Molecular Biology; SCI(E); 8; ARTICLE; guifangjia@pku.edu.cn; cluo@simm.ac.cn; yangcg@simm.ac.cn; 1; 373-384; 43
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/386693]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Huang, Yue,Yan, Jingli,Li, Qi,et al. Meclofenamic acid selectively inhibits FTO demethylation of m(6)A over ALKBH5[J]. 核酸研究,2015.
APA	Huang, Yue.,Yan, Jingli.,Li, Qi.,Li, Jiafei.,Gong, Shouzhe.,...&Yang, Cai-Guang.(2015).Meclofenamic acid selectively inhibits FTO demethylation of m(6)A over ALKBH5.核酸研究.
MLA	Huang, Yue,et al."Meclofenamic acid selectively inhibits FTO demethylation of m(6)A over ALKBH5".核酸研究 (2015).