Nature:核糖体的催化活性

核糖体的催化中心完全由RNA组成。这意味着,它没有在能够帮助催化的蛋白中所见的不同侧基,所以过去人们认为它的功能仅仅是将mRNA和带电的tRNA带到附近。但事实并不是这样的。对 “肽基转移RNA”的反应中心内5个位置上的动态同位素效应的分析显示,核糖体通过修饰限速过渡状态来增强对肽键形成的催化。这一发现对于有关生命起源以及关于生命从RNA世界的过渡的研究有参考意义。

 

英文摘要

A two-step chemical mechanism for ribosome-catalysed peptide bond formation

The chemical step of natural protein synthesis, peptide bond formation, is catalysed by the large subunit of the ribosome. Crystal structures have shown that the active site for peptide bond formation is composed entirely of RNA. Recent work has focused on how an RNA active site is able to catalyse this fundamental biological reaction at a suitable rate for protein synthesis. On the basis of the absence of important ribosomal functional groups, lack of a dependence on pH, and the dominant contribution of entropy to catalysis, it has been suggested that the role of the ribosome is limited to bringing the substrates into close proximity. Alternatively, the importance of the 2′-hydroxyl of the peptidyl-transfer RNA and a Brønsted coefficient near zero have been taken as evidence that the ribosome coordinates a proton-transfer network. Here we report the transition state of peptide bond formation, based on analysis of the kinetic isotope effect at five positions within the reaction centre of a peptidyl-transfer RNA mimic. Our results indicate that in contrast to the uncatalysed reaction, formation of the tetrahedral intermediate and proton transfer from the nucleophilic nitrogen both occur in the rate-limiting step. Unlike in previous proposals, the reaction is not fully concerted; instead, breakdown of the tetrahedral intermediate occurs in a separate fast step. This suggests that in addition to substrate positioning, the ribosome is contributing to chemical catalysis by changing the rate-limiting transition state.

 

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