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发夹状核酶:从晶体结构到功能

The hairpin ribozyme: from crystal structure to function.

作者信息

Ferré-D'amaré A R, Rupert P B

机构信息

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109-1024, USA.

出版信息

Biochem Soc Trans. 2002 Nov;30(Pt 6):1105-9. doi: 10.1042/bst0301105.

DOI:10.1042/bst0301105
PMID:12440983
Abstract

The hairpin ribozyme is one of four known natural catalytic RNAs that carry out sequence-specific cleavage of RNA. It is of particular biochemical interest because, unlike 'classic' ribozymes, such as the group I intron, it appears not to employ metal ions as catalytic cofactors. We have determined the crystal structure of a hairpin-ribozyme-inhibitor complex at a resolution of 2.4 A. The active site of the ribozyme results from docking of two irregular double helices. Docking results in major structural rearrangements of the helices, including a distortion of the substrate strand that brings it into a reactive conformation. It remains to be established whether this RNA enzyme relies exclusively on binding energy to carry out catalysis, or whether some other mechanism, such as general acid-base catalysis, is being employed.

摘要

发夹状核酶是已知的四种天然催化RNA之一,可对RNA进行序列特异性切割。它具有特殊的生化意义,因为与“经典”核酶(如I类内含子)不同,它似乎不使用金属离子作为催化辅因子。我们已确定了一种发夹状核酶-抑制剂复合物的晶体结构,分辨率为2.4埃。核酶的活性位点由两个不规则双螺旋对接形成。对接导致螺旋发生重大结构重排,包括底物链的扭曲,使其进入反应构象。这种RNA酶是仅依靠结合能进行催化,还是采用了其他机制(如一般酸碱催化),仍有待确定。

相似文献

1
The hairpin ribozyme: from crystal structure to function.发夹状核酶:从晶体结构到功能
Biochem Soc Trans. 2002 Nov;30(Pt 6):1105-9. doi: 10.1042/bst0301105.
2
Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis.具有催化作用意义的发夹状核酶 - 抑制剂复合物的晶体结构
Nature. 2001 Apr 12;410(6830):780-6. doi: 10.1038/35071009.
3
Kinetics and thermodynamics of intermolecular catalysis by hairpin ribozymes.发夹状核酶分子间催化作用的动力学与热力学
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The catalytic mechanism of the hairpin ribozyme.发夹状核酶的催化机制。
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Extensive molecular dynamics simulations showing that canonical G8 and protonated A38H+ forms are most consistent with crystal structures of hairpin ribozyme.广泛的分子动力学模拟表明,规范的 G8 和质子化的 A38H+形式与发夹核酶晶体结构最一致。
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An unusual pH-independent and metal-ion-independent mechanism for hairpin ribozyme catalysis.锤头状核酶催化的一种不寻常的与pH和金属离子无关的机制。
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Inter-domain cross-linking and molecular modelling of the hairpin ribozyme.发夹状核酶的结构域间交联与分子建模
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The antisense sequence of the HIV-1 TAR stem-loop structure covalently linked to the hairpin ribozyme enhances its catalytic activity against two artificial substrates.与发夹状核酶共价连接的HIV-1 TAR茎环结构的反义序列增强了其对两种人工底物的催化活性。
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Intermolecular domain docking in the hairpin ribozyme: metal dependence, binding kinetics and catalysis.发夹状核酶中的分子间结构域对接:金属依赖性、结合动力学和催化作用。
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