Adaptive ligand binding by the purine riboswitch in the recognition of guanine and adenine analogs.
Adaptive ligand binding by the purine riboswitch in the recognition of guanine and adenine analogs.
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DOI：
10.1016/j.str.2009.04.009
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发表时间：
2009-06-10
期刊：
影响因子：
--
通讯作者：
Batey RT
中科院分区：
文献类型：
--
作者：
Gilbert SD;Reyes FE;Edwards AL;Batey RT
嘌呤核糖开关基于一个与配体形成沃森 - 克里克碱基对的单一嘧啶（Y74）的特性，对鸟嘌呤和腺嘌呤的区分能力至少达到10000倍。为了解这种对密切相关化合物的高度特异性是如何通过简单的碱基配对实现的，我们研究了它们与在2位和6位具有不同官能团且有可能改变与Y74相互作用的嘌呤类似物的相互作用。通过结合晶体学和量热学方法，我们发现这些嘌呤的结合通常是通过RNA的微小结构变化或配体的互变异构变化来促进的。这项工作还表明，除了碱基配对，Y74的构象限制对核碱基选择性有显著贡献。这些结果揭示，利用核糖开关结合口袋内固有的局部灵活性的化合物能够改变其配体特异性。
Purine riboswitches discriminate between guanine and adenine by at least 10,000-fold based on the identity of a single pyrimidine (Y74) that forms a Watson-Crick base pair with the ligand. To understand how this high degree of specificity for closely related compounds is achieved through simple pairing, we investigated their interaction with purine analogs with varying functional groups at the 2- and 6-positions that have the potential to alter interactions with Y74. Using a combination of crystallographic and calorimetric approaches, we find that binding these purines is often facilitated by either small structural changes in the RNA or tautomeric changes in the ligand. This work also reveals that, along with base pairing, conformational restriction of Y74 significantly contributes to nucleobase selectivity. These results reveal that compounds that exploit the inherent local flexibility within riboswitch binding pockets can alter their ligand specificity.
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影响因子：
64.5
作者：
Johnson, SJ;Beese, LS
通讯作者：
Beese, LS
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
影响因子：
5.7
作者：
Edwards, Thomas E.;Ferre-D'Amare, Adrian R.
通讯作者：
Ferre-D'Amare, Adrian R.
影响因子：
5.6
作者：
Guilbert, Christophe;James, Thomas L.
通讯作者：
James, Thomas L.
DOI：
10.1073/pnas.0407607101
发表时间：
2004-11-30
影响因子：
11.1
作者：
Auffinger, P;Hays, FA;Ho, PS
通讯作者：
Ho, PS