Structure-based mechanistic insights into catalysis by small self-cleaving ribozymes.

Structure-based mechanistic insights into catalysis by small self-cleaving ribozymes.
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基于结构的小型自裂解核酶催化机制的见解

DOI:
10.1016/j.cbpa.2017.09.017
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发表时间:
2017-12
影响因子:
7.8
通讯作者:
Patel DJ
Patel DJ
中科院分区:
生物学2区
文献类型:
--
作者:
Ren A;Micura R;Patel DJ

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小的自切割核酶广泛分布于自然界,对卫星rna和致病rna的滚环复制至关重要。早期对锤头、发夹、glmS、丁型肝炎病毒和Varkud卫星核酶的结构-功能研究已经提供了对它们的总体结构、催化活性位点组织以及附近核碱基和水合二价阳离子在促进一般酸碱和静电介导催化中的作用的见解。本文综述了Rzb锤头核酶的活性位点比对和催化机制,以及新发现的手枪核酶、twister核酶和twister-sister核酶的结构功能研究进展。与对Rzb锤头核酶和手枪核酶的自裂解机制的一致理解相反,对涡旋核酶和涡旋核酶所采用的裂解位点定位和催化机制存在分歧。解决这一难题的一种方法是将结构研究从目前可用的预催化构象扩展到两种核酶的过渡态模拟钒酸盐对应物。
Small self-cleaving ribozymes are widely distributed in nature and are essential for rolling-circle-based replication of satellite and pathogenic RNAs. Earlier structure-function studies on the hammerhead, hairpin, glmS, hepatitis delta virus and Varkud satellite ribozymes have provided insights into their overall architecture, their catalytic active site organization, and the role of nearby nucleobases and hydrated divalent cations in facilitating general acid-base and electrostatic-mediated catalysis. This review focuses on recent structure-function research on active site alignments and catalytic mechanisms of the Rzb hammerhead ribozyme, as well as newly-identified pistol, twister and twister-sister ribozymes. In contrast to an agreed upon mechanistic understanding of self-cleavage by Rzb hammerhead and pistol ribozymes, there exists a divergence of views as to the cleavage site alignments and catalytic mechanisms adopted by twister and twister-sister ribozymes. One approach to resolving this conundrum would be to extend the structural studies from currently available pre-catalytic conformations to their transition state mimic vanadate counterparts for both ribozymes.
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