A new twist revealed for ribozyme catalysis | Chemical & Engineering News
Volume 94 Issue 12 | p. 12 | Concentrates
Issue Date: March 21, 2016

A new twist revealed for ribozyme catalysis

Computational simulations suggest mechanism by which twister ribozymes cleave themselves
Department: Science & Technology
News Channels: Biological SCENE, JACS In C&EN
Keywords: biochemistry, ribozyme, RNA catalysis, twister
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In the proposed mechanism for twister ribozyme self-cleavage (red), a guanine N1 hydrogen-bonds (blue) to the uracil 2’-OH, promoting it as a nucleophile. The protonated adenine N3 hydrogen-bonds to its own 5’-O (green), promoting it as a leaving group.
Structures showing twister ribozyme guanine, uracil, and adenine interactions.
 
In the proposed mechanism for twister ribozyme self-cleavage (red), a guanine N1 hydrogen-bonds (blue) to the uracil 2’-OH, promoting it as a nucleophile. The protonated adenine N3 hydrogen-bonds to its own 5’-O (green), promoting it as a leaving group.

RNAs called ribozymes can catalyze chemical reactions and often play a role in regulating gene expression. Twister ribozymes, which get their name because their overall structure resembles an ancient Egyptian hieroglyph representing twisted flax, are widespread in bacteria and eukaryotes and cut their own phosphodiester backbone. They may accomplish that cleavage through a novel acid catalysis mechanism, according to computational simulations presented at the meeting by Darrin M. York of Rutgers University. Twister ribozymes crystallize in an inactive conformation, which has made it difficult to determine how they self-cleave between adjacent uracil and adenine residues. York and graduate student Colin S. Gaines simulated both the crystalline and solution forms of a twister ribozyme (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.5b12061). The chemists found that in solution the uracil can adopt an active conformation in which it stacks with a nearby guanine. The guanine N1 may then hydrogen-bond to the uracil 2’-OH, promoting it as a nucleophile to attack a neighboring phosphate. Meanwhile, the adenine N3 is protonated and can hydrogen-bond to its own 5’-O, promoting it as a leaving group. Although the N1 of adenine residues has been implicated in catalysis by other ribozymes, such a role has not previously been suggested for N3.

 
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