...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >RNA methylation by Radical SAM enzymes RImN and Cfr proceeds via methylene transfer and hydride shift
【24h】

RNA methylation by Radical SAM enzymes RImN and Cfr proceeds via methylene transfer and hydride shift

机译：自由基SAM酶RImN和Cfr的RNA甲基化通过亚甲基转移和氢化物转移进行

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

RlmN and Cfr are Radical SAM enzymes that modify a single ade-nosine nucleotide-A2503-in 23S ribosomal RNA. This nucleotide is positioned within the peptidyl transferase center of the ribo-some, which is a target of numerous antibiotics. An unusual feature of these enzymes is their ability to carry out methylation of amidine carbons of the adenosine substrate. To gain insight into the mechanism of methylation catalyzed by RImN and Cfr, deuterium labeling experiments were carried out. These experiments demonstrate that the newly introduced methyl group is assembled from an S-adenosyl-L-methionine (SAM)-derived methylene fragment and a hydrogen atom that had migrated from the substrate amidine carbon. Rather than activating the adenosine nucleotide of the substrate by hydrogen atom abstraction from an amidine carbon, the 5 -deoxyadenosyl radical abstracts hydrogen from the second equivalent of SAM to form the SAM-derived radical cation. This species, or its corresponding sulfur ylide, subsequently adds into the substrate, initiating hydride shift and 5-adenosylho-mocysteine elimination to complete the formation of the methyl group. These findings indicate that rather than acting as methyl-transferases, RlmN and Cfr are methyl synthases. Together with the previously described 5-deoxyadenosyl and 3-amino-3-carboxypropyl radicals, these findings demonstrate that all three carbon atoms attached to the sulfonium center in SAM can serve as precursors to carbon-derived radicals in enzymatic reactions.
机译：RlmN和Cfr是自由基SAM酶，可修饰23S核糖体RNA中的单个腺苷核苷酸A2503-。该核苷酸位于核糖体的肽基转移酶中心，核糖体是众多抗生素的靶标。这些酶的一个不寻常的特征是它们使腺苷底物的am碳进行甲基化的能力。为了深入了解RImN和Cfr催化甲基化的机理，进行了氘标记实验。这些实验表明，新引入的甲基由S-腺苷-L-蛋氨酸（SAM）衍生的亚甲基片段和已从底物am碳迁移的氢原子组装而成。 5-脱氧腺苷基团不是通过从carbon碳中夺取氢原子来活化底物的腺苷核苷酸，而是从第二当量的SAM中提取氢以形成SAM衍生的自由基阳离子。该物质或其相应的硫叶立德随后加入底物中，开始氢化物转移和5-腺苷-高半胱氨酸消除，从而完成了甲基的形成。这些发现表明，RlmN和Cfr不是甲基转移酶，而是甲基合酶。这些发现与前述的5-脱氧腺苷基和3-氨基-3-羧丙基基团一起证明，在SAM中连接到to中心的所有三个碳原子都可以用作酶促反应中碳衍生基团的前体。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号