Chemical Feasibility of the General Acid/Base Mechanism of glmS Ribozyme Self-Cleavage

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F15%3A33156432" target="_blank" >RIV/61989592:15310/15:33156432 - isvavai.cz</a>

Alternative codes found

RIV/68081707:_____/15:00447582 RIV/00216224:14740/15:00083966

Result on the web

<a href="http://onlinelibrary.wiley.com/enhanced/doi/10.1002/bip.22657/" target="_blank" >http://onlinelibrary.wiley.com/enhanced/doi/10.1002/bip.22657/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/bip.22657" target="_blank" >10.1002/bip.22657</a>

Result language

angličtina

Original language name

Chemical Feasibility of the General Acid/Base Mechanism of glmS Ribozyme Self-Cleavage

Original language description

In numerous Gram-positive bacteria, the glmS ribozyme or catalytic riboswitch regulates the expression of glucosamine-6-phosphate (GlcN6P) synthase via site-specific cleavage of its sugar-phosphate backbone in response to GlcN6P ligand binding. Biochemical data have suggested a crucial catalytic role for an active site guanine (G40 in Thermoanaerobacter tengcongensis, G33 in Bacillus anthracis). We used hybrid quantum chemical/molecular mechanical (QM/MM) calculations to probe the mechanism where G40 is deprotonated and acts as a general base. The calculations suggest that the deprotonated guanine G40(-) is sufficiently reactive to overcome the thermodynamic penalty arising from its rare protonation state, and thus is able to activate the A-1(2-OH) group toward nucleophilic attack on the adjacent backbone. Furthermore, deprotonation of A-1(2-OH) and nucleophilic attack are predicted to occur as separate steps, where activation of A-1(2-OH) precedes nucleophilic attack. Conversely, the transition state associated with the rate-determining step corresponds to concurrent nucleophilic attack and protonation of the G1(O5) leaving group by the ammonium moiety of the GlcN6P cofactor. Overall, our calculations help to explain the crucial roles of G40 (as a general base) and GlcN6P (as a general acid) during glmS ribozyme self-cleavage. In addition, we show that the QM/MM description of the glmS ribozyme self-cleavage reaction is significantly more sensitive to the size of the QM region and the quality of the QM-MM coupling than that of other small ribozymes. (c) 2015 Wiley Periodicals, Inc.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biopolymers

ISSN

0006-3525

e-ISSN

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Volume of the periodical

103

Issue of the periodical within the volume

10

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

550-562

UT code for WoS article

000358620900002

EID of the result in the Scopus database

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