热门
Meclofenamic acid selectively inhibits FTO demethylation of m(6)A over ALKBH5
文献类型：期刊论文
| 作者 | Huang, Yue1; Yan, Jingli2; Li, Qi1; Li, Jiafei1; Gong, Shouzhe1; Zhou, Hu1 ; Gan, Jianhua3; Jiang, Hualiang4; Jia, Gui-Fang2; Luo, Cheng4
|
| 刊名 | NUCLEIC ACIDS RESEARCH
 |
| 出版日期 | 2015-01 |
| 卷号 | 43期号:1页码:373-384 |
| ISSN号 | 0305-1048 |
| DOI | 10.1093/nar/gku1276 |
| 文献子类 | Article |
| 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. |
| WOS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 |
| 资助项目 | National Natural Science Foundation of China[91313303] ; National Natural Science Foundation of China[21372237] ; National Natural Science Foundation of China[21372022] ; National Natural Science Foundation of China[21210003] ; National Basic Research Program[2015CB910603] ; Hi-Tech Research and Development Program of China[2012AA020302] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000350207100037 |
| 出版者 | OXFORD UNIV PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276752]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第三研究室 |
| 通讯作者 | Yang, Cai-Guang |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China; 2.Peking Univ, Synthet & Funct Biomol Ctr, Key Lab Bioorgan Chem & Mol Engn, Beijing Natl Lab Mol Sci,Minist Educ,Coll Chem &, Beijing 100871, Peoples R China; 3.Fudan Univ, Sch Life Sci, Shanghai 200433, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 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]. NUCLEIC ACIDS RESEARCH,2015,43(1):373-384. |
| 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.NUCLEIC ACIDS RESEARCH,43(1),373-384. |
| MLA | Huang, Yue,et al."Meclofenamic acid selectively inhibits FTO demethylation of m(6)A over ALKBH5".NUCLEIC ACIDS RESEARCH 43.1(2015):373-384. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。