院士大讲堂
报告题目：The extent of RNA catalysis – are there any limits?
报告时间：2023-06-13 15:00
报告人： Prof. David Lilley
University of Dundee, Dundee, UK
报告地点：思明校区台湾研究院5楼学术报告厅
转播：翔安校区能源材料大楼3号楼会议室5，漳州校区生化主楼307教室
报告摘要：
The RNA world hypothesis for the early development of life on the planet requires that RNA molecules (ribozymes) could have catalysed a wide variety of chemical reactions. Known ribozymes in contemporary biology carry out a limited range of chemical catalysis, mostly involving phosphoryl transfer, but in vitro selection has generated species catalysing a broader range of chemistry. To gauge the feasibility of an RNA world it is useful to explore if ribozymes can exploit sophisticated catalytic strategies. A ribozyme has recently been selected that can catalyse a methyl transfer reaction using O6-methylguanine as donor. We have solved the crystal structure of this ribozyme at a resolution of 2.3 Å, showing how the RNA folds to generate a very specific binding site for the methyl donor substrate. The structure immediately suggests a catalytic mechanism, involving a combination of proximity and orientation, and nucleobase-mediated general acid catalysis. The mechanism is supported by the pH dependence of the rate of catalysis, and by quantum mechanical calculation. This small chemical machine employs a relatively sophisticated catalytic mechanism, broadening the range of known RNA-catalysed chemistry. This lends new support to the RNA world hypothesis Going still further, how could RNA overcome its relative chemical simplicity and expand its catalytic repertoire? The RNA world would have required a much broader range of RNA catalyzed chemistry, including “difficult” reactions like making C-C bonds. Modern protein enzymes achieve this by using co-enzymes, and perhaps RNA could do the same. RNA is a superb receptor for small molecules, as exemplified by the riboswitches. A significant number of these bind coenzymes, including SAM, TPP, NAD+ and FMN, and it’s not a big leap to imagine that the riboswitch might have evolved from an ancient ribozyme, or might be converted into a novel ribozyme.
报告人简介：
David Lilley教授，英国皇家学会院士，在核酸的结构及功能研究方面具有很深的造诣，已在Science，Nature, J. Am. Chem. Soc. Cell, PNAS, Structure 等国际一流期刊发表文章380余篇，并获得很多荣誉，其中包括英国皇家化学学会交叉学科奖，RNA and Ribozyme Chemistry Award of The Royal Society of Chemistry， The Prelog Medal in Stereochemistry, Zurich, Switzerland，The Gold Medal of G. Mendel of the Czech Academy of Sciences 等国际知名奖项。2015年获得RNA学会终身成就奖，2016年荣获皇家化学学会霍拉纳奖（Awarded the Royal Society of Chemistry Khorana Prize）。
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