Altering molecular recognition of RNA aptamers by allosteric selection
Altering molecular recognition of RNA aptamers by allosteric selection
复制标题
DOI：
10.1006/jmbi.2000.3704
复制
发表时间：
2000-05-12
影响因子：
5.6
通讯作者：
Breaker, RR
中科院分区：
文献类型：
--
作者：
Soukup, GA;Emilsson, GAM;Breaker, RR
在不断努力探索RNA催化的结构和功能动力学，我们已经创建了一系列的变构锤头状核酶，茶碱激活。代表性的核酶表现出大于3000倍的激活后效应结合和切割的最大速率常数，相当于未修饰的锤头状核酶。此外，我们已经进化出一种变体变构核酶，其表现出从茶碱到S-甲基黄嘌呤的效应特异性变化。这两个效应分子之间的歧视似乎是介导的微妙的构象差异，源自附近的效应结合口袋的磷酸二酯骨架的位移。这些发现揭示了核酸分子识别的深奥方面的重要性，这些方面很可能是目前理性设计方法所无法达到的。(C)北京大学出版社.
In a continuing effort to explore structural and functional dynamics in RNA catalysis, we have created a series of allosteric hammerhead ribozymes that are activated by theophylline. Representative ribozymes exhibit greater than 3000-fold activation upon effector-binding and cleave with maximum rate constants that are equivalent to the unmodified hammerhead ribozyme. In addition, we have evolved a variant allosteric ribozyme that exhibits an effector specificity change from theophylline to S-methylxanthine. Molecular discrimination between the two effecters appears to be mediated by subtle conformational differences that originate from displacement of the phosphodiester backbone near the effector binding pocket. These findings reveal the importance of abstruse aspects of molecular recognition by nucleic acids that are likely to be unapproachable by current methods of rational design. (C) 2000 Academic Press.