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锤头状核酶中的单个突变有利于在使用锰而非镁的情况下进行切割活性。

Single Mutation in Hammerhead Ribozyme Favors Cleavage Activity with Manganese over Magnesium.

作者信息

Naghdi Mohammad Reza, Boutet Emilie, Mucha Clarisse, Ouellet Jonathan, Perreault Jonathan

机构信息

Institut National de la Recherche Scientifique (INRS), Centre Armand Frappier Santé Biotechnologie, 531 boul. des Prairies, Laval, QB H7V 1B7, Canada.

Department of Chemistry and Physics, Monmouth University, 400 Cedar Avenue, West Long Branch, NJ 07764, USA.

出版信息

Noncoding RNA. 2020 Mar 20;6(1):14. doi: 10.3390/ncrna6010014.

DOI:10.3390/ncrna6010014
PMID:32245091
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7151607/
Abstract

Hammerhead ribozymes are one of the most studied classes of ribozymes so far, from both the structural and biochemical point of views. The activity of most hammerhead ribozymes is cation-dependent. Mg is one of the most abundant divalent cations in the cell and therefore plays a major role in cleavage activity for most hammerhead ribozymes. Besides Mg, cleavage can also occur in the presence of other cations such as Mn. The catalytic core of hammerhead ribozymes is highly conserved, which could contribute to a preference of hammerhead ribozymes toward certain cations. Here, we show a naturally occurring variation in the catalytic core of hammerhead ribozymes, A6C, that can favor one metallic ion, Mn, over several other cations.

摘要

从结构和生化角度来看,锤头状核酶是迄今为止研究最多的核酶类别之一。大多数锤头状核酶的活性依赖于阳离子。镁是细胞中最丰富的二价阳离子之一,因此在大多数锤头状核酶的切割活性中起主要作用。除了镁之外,在其他阳离子(如锰)存在的情况下也会发生切割。锤头状核酶的催化核心高度保守,这可能导致锤头状核酶对某些阳离子有偏好。在这里,我们展示了锤头状核酶催化核心中一种天然存在的变异,即A6C,它相比于其他几种阳离子,更倾向于一种金属离子——锰。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/3f95c8c4b3ce/ncrna-06-00014-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/6b7f3063c799/ncrna-06-00014-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/1856980ceda7/ncrna-06-00014-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/9fa9f56797f5/ncrna-06-00014-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/3f95c8c4b3ce/ncrna-06-00014-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/6b7f3063c799/ncrna-06-00014-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/1856980ceda7/ncrna-06-00014-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/9fa9f56797f5/ncrna-06-00014-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d9eb/7151607/3f95c8c4b3ce/ncrna-06-00014-g004.jpg

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本文引用的文献

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Bulky cations greatly increase the turnover of a native hammerhead ribozyme.体积较大的阳离子极大地提高了天然锤头状核酶的周转率。
RSC Adv. 2019 Nov 4;9(61):35820-35824. doi: 10.1039/c9ra06797c. eCollection 2019 Oct 31.
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Novel ribozymes: discovery, catalytic mechanisms, and the quest to understand biological function.新型核酶:发现、催化机制以及对生物功能理解的探索。
Nucleic Acids Res. 2019 Oct 10;47(18):9480-9494. doi: 10.1093/nar/gkz737.
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Convergent Use of Heptacoordination for Cation Selectivity by RNA and Protein Metalloregulators.
RNA 和蛋白质金属调节因子通过七配位实现阳离子选择性。
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The Hammerhead Ribozyme: A Long History for a Short RNA.锤头状核酶:一种短RNA的漫长历史
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A divalent cation-dependent variant of the ribozyme with stringent Ca selectivity co-opts a preexisting nonspecific metal ion-binding site.具有严格钙选择性的核酶的二价阳离子依赖性变体利用了一个预先存在的非特异性金属离子结合位点。
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Two Active Site Divalent Ions in the Crystal Structure of the Hammerhead Ribozyme Bound to a Transition State Analogue.与过渡态类似物结合的锤头状核酶晶体结构中的两个活性位点二价离子。
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Two Divalent Metal Ions and Conformational Changes Play Roles in the Hammerhead Ribozyme Cleavage Reaction.两个二价金属离子和构象变化在锤头状核酶切割反应中发挥作用。
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