Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase
文献类型：期刊论文
| 作者 | Yi, Chengqi2,5; Jia, Guifang2,5; Hou, Guanhua3,4; Dai, Qing1; Zhang, Wen2,5; Zheng, Guanqun2,5; Jian, Xing2,5; Yang, Cai-Guang2,5,6 ; Cui, Qiang3,4; He, Chuan2,5
|
| 刊名 | NATURE
 |
| 出版日期 | 2010-11-11 |
| 卷号 | 468期号:7321页码:330-U223 |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature09497 |
| 文献子类 | Article |
| 英文摘要 | Mononuclear iron-containing oxygenases conduct a diverse variety of oxidationfunctions in biology(1,2), includingthe oxidative demethylation of methylated nucleic acids and histones(3,4). Escherichia coli AlkB is the first such enzyme that was discovered to repair methylated nucleic acids(5,6), which are otherwise cytotoxic and/or mutagenic. AlkB human homologues are known to play pivotal roles in various processes(7-11). Here we present structural characterization of oxidation intermediates for these demethylases. Using a chemical cross-linking strategy(12,13), complexes of AlkB-double stranded DNA (dsDNA) containing 1,N-6-etheno adenine (epsilon A), N-3-methyl thymine (3-meT) and N-3-methyl cytosine (3-meC) are stabilized and crystallized, respectively. Exposing these crystals, grown under anaerobic conditions containing iron(II) and alpha-ketoglutarate (alpha KG), to dioxygen initiates oxidation in crystallo. Glycol (from epsilon A) and hemiaminal (from 3-meT) intermediates are captured; a zwitterionic intermediate (from 3-meC) is also proposed, based on crystallographic observations and computational analysis. The observation of these unprecedented intermediates provides direct support for the oxidative demethylation mechanism for these demethylases. This study also depicts a general mechanistic view of how a methyl group is oxidatively removed from different biological substrates. |
| WOS关键词 | BASE-EXCISION-REPAIR ; ESCHERICHIA-COLI ; CRYSTAL-STRUCTURES ; ALKB PROTEINS ; ENZYME ALKB ; FTO GENE ; DEMETHYLATION ; DAMAGE ; 3-METHYLTHYMINE ; RECOGNITION |
| 资助项目 | National Institutes of Health[GM071440] ; National Institutes of Health[GM084028] ; Advanced Photon Source at Argonne National Laboratory[00000000] ; United States Department of Energy[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000284051000056 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278721]  |
| 专题 | 药理学第三研究室 |
| 通讯作者 | He, Chuan |
| 作者单位 | 1.Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA; 2.Univ Chicago, Dept Chem, Chicago, IL 60637 USA; 3.Univ Wisconsin, Inst Theoret Chem, Madison, WI 53706 USA; 4.Univ Wisconsin, Dept Chem, Madison, WI 53706 USA; 5.Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA; 6.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yi, Chengqi,Jia, Guifang,Hou, Guanhua,et al. Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase[J]. NATURE,2010,468(7321):330-U223. |
| APA | Yi, Chengqi.,Jia, Guifang.,Hou, Guanhua.,Dai, Qing.,Zhang, Wen.,...&He, Chuan.(2010).Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase.NATURE,468(7321),330-U223. |
| MLA | Yi, Chengqi,et al."Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase".NATURE 468.7321(2010):330-U223. |
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。