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Structure and mechanism of a methyltransferase ribozyme
Nature Chemical Biology ( IF 14.8 ) Pub Date : 2022-03-17 , DOI: 10.1038/s41589-022-00982-z
Jie Deng 1, 2 , Timothy J Wilson 3 , Jia Wang 4 , Xuemei Peng 1, 2 , Mengxiao Li 1, 2 , Xiaowei Lin 1, 5 , Wenjian Liao 1, 5 , David M J Lilley 3 , Lin Huang 1, 2
Affiliation  

Known ribozymes in contemporary biology perform a limited range of chemical catalysis, but in vitro selection has generated species that catalyze a broader range of chemistry; yet, there have been few structural and mechanistic studies of selected ribozymes. A ribozyme has recently been selected that can catalyze a site-specific methyl transfer reaction. We have solved the crystal structure of this ribozyme at a resolution of 2.3 Å, showing how the RNA folds to generate a very specific binding site for the methyl donor substrate. The structure immediately suggests a catalytic mechanism involving a combination of proximity and orientation and nucleobase-mediated general acid catalysis. The mechanism is supported by the pH dependence of the rate of catalysis. A selected methyltransferase ribozyme can thus use a relatively sophisticated catalytic mechanism, broadening the range of known RNA-catalyzed chemistry.



中文翻译:

甲基转移酶核酶的结构和机制

当代生物学中已知的核酶进行有限范围的化学催化,但体外选择产生了催化更广泛化学范围的物种;然而,对选定核酶的结构和机制研究很少。最近选择了一种可以催化位点特异性甲基转移反应的核酶。我们已经以 2.3 Å 的分辨率解析了这种核酶的晶体结构,显示了 RNA 如何折叠以生成甲基供体底物的非常特异性的结合位点。该结构立即表明了一种催化机制,涉及接近和定向以及核碱基介导的一般酸催化的组合。该机制由催化速率的 pH 依赖性支持。

更新日期:2022-03-17
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