Structure and Function Converge To Identify a Hydrogen Bond in a Group I Ribozyme Active Site
Structure and Function Converge To Identify a Hydrogen Bond in a Group I Ribozyme Active Site
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DOI：
10.1002/anie.200903006
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发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Herschlag, Daniel
中科院分区：
文献类型：
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作者：
Forconi, Marcello;Sengupta, Raghuvir N.;Herschlag, Daniel
要确定酶如何实现其催化能力，需要了解结构基序是如何用来在活性部位定位酶和底物的功能基团的。最近RNA晶体结构的爆炸为深入研究核酶结构和功能之间的关系提供了一个非同寻常的机会。四膜虫组核酶因其丰富的结构信息，为此类研究提供了一个极具吸引力的系统，在过去的五年中解决了I族内含子的10个晶体结构，[1-5]和广泛的功能信息，使深入分析催化剂的能量成为可能。四膜虫I族核酶催化磷酸转移反应，模拟I族内含子自剪接的第一步(方案1)。[6，7]这个反应涉及两个底物，一个寡核苷酸(S)和一个外源鸟苷分子。S首先通过碱基配对[8]与核酶结合，形成方案1中的“开放复合体”“o”，然后对接到核酶的活性部位[9，10]，形成方案1中“闭合复合体”“c”中的三级相互作用。鸟苷还以高度保守的专属位点与核酶结合，底物可以
The determination of how enzymes achieve their catalytic power requires an understanding of how structural motifs are used to position functional groups of enzymes and substrates within active sites. The recent explosion of RNA crystal structures provides an extraordinary opportunity to delve deeply into the relationship between ribozyme structure and function. The Tetrahymena groupI ribozyme provides an attractive system for such studies because of the wealth of structural information, with ten crystal structures of group I introns solved in the past five years,[1–5] and extensive functional information [6] that enables incisive analysis of the energetics of catalysis.The Tetrahymena group I ribozyme catalyzes a phosphoryl-transfer reaction that mimics the first step of self-splicing of group I introns (Scheme 1).[6, 7] This reaction involves two substrates, an oligonucleotide (S) and an exogenous guanosine molecule. S binds to the ribozyme first by base pairing [8] to form the “open complex”“o” in Scheme 1, and then docks into the active site of the ribozyme [9, 10] to form tertiary interactions in the “closed complex”“c” in Scheme1. Guanosine also binds to the ribozyme in a dedicated, highly conserved site,[1–3, 11] and the substrates can