The glmS ribozyme cofactor is a general acid-base catalyst.
The glmS ribozyme cofactor is a general acid-base catalyst.
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DOI：
10.1021/ja307021f
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发表时间：
2012-11-21
影响因子：
15
通讯作者：
Fedor MJ
中科院分区：
文献类型：
--
作者：
Viladoms J;Fedor MJ
glmS核酶是已知的第一个需要辅因子的天然自裂核酶。d -氨基葡萄糖-6-磷酸（GlcN6P）辅助因子被认为是一种通用酸，但其在催化机制中的作用尚未确定。我们研究了glcn6p样分子支持glmS核酶自裂解的能力，发现裂解反应的pH依赖性与辅因子的内在酸度之间存在很强的相关性。对于结合亲和力较低的辅因子，对速率提高的贡献与其固有酸度成正比。辅助因子效率与酸解离常数之间的线性自由能关系与辅助因子作为一般酸碱催化剂直接参与反应的机理一致。高Brønsted系数（β ~ 0.7）表明在过渡态已经发生了大量的质子转移。glmS核酶是第一个使用外源性酸碱催化剂的自切割RNA。
The glmS ribozyme is the first natural self-cleaving ribozyme known to require a cofactor. The D-glucosamine-6-phosphate (GlcN6P) cofactor has been proposed to serve as a general acid, but its role in the catalytic mechanism has not been established conclusively. We surveyed GlcN6P-like molecules for their ability to support self-cleavage of the glmS ribozyme and found a strong correlation between the pH dependence of the cleavage reaction and the intrinsic acidity of the cofactors. For cofactors with low binding affinities the contribution to rate enhancement was proportional to their intrinsic acidity. This linear free-energy relationship between cofactor efficiency and acid dissociation constants is consistent with a mechanism in which the cofactors participate directly in the reaction as general acid-base catalysts. A high value for the Brønsted coefficient (β ~ 0.7) indicates that a significant amount of proton transfer has already occurred in the transition state. The glmS ribozyme is the first self-cleaving RNA to use an exogenous acid-base catalyst.
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DOI：
10.1073/pnas.98.4.1489
发表时间：
2001-02-13
影响因子：
11.1
作者：
Shih, I;Been, MD
通讯作者：
Been, MD
影响因子：
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影响因子：
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影响因子：
56.9
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