Mapping the Chemical Space of the RNA Cleavage and Its Implications for Ribozyme Catalysis

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F17%3A73584572" target="_blank" >RIV/61989592:15310/17:73584572 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/17:00486054

Výsledek na webu

<a href="http://pubs.acs.org/doi/10.1021/acs.jpcb.7b09129" target="_blank" >http://pubs.acs.org/doi/10.1021/acs.jpcb.7b09129</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jpcb.7b09129" target="_blank" >10.1021/acs.jpcb.7b09129</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mapping the Chemical Space of the RNA Cleavage and Its Implications for Ribozyme Catalysis

Popis výsledku v původním jazyce

Ribozymes utilize diverse catalytic strategies. We report systematic quantum chemical calculations mapping the catalytic space of RNA cleavage by comparing all chemically feasible reaction mechanisms of RNA self-cleavage, using appropriate model systems including those chemical groups that may directly participate in ribozyme catalysis. We calculated the kinetics of uncatalyzed cleavage reactions proceeding via both monoanionic and dianionic pathways, and explicitly probed effects of various groups acting as general bases (GBs) and/or general acids (GAs), or electrostatic transition state stabilizers. In total, we explored 115 different mechanisms. The dianionic scenarios are generally preferred to monoanionic scenarios, although they may compete with one-another under some conditions. Direct GA catalysis seems to exert the dominant catalytic effect, while GB catalysis electrostatic stabilization are less efficient. Our results indirectly suggest that the dominant part of the catalytic effect might be explained by the shift of the reaction mechanism from the mechanism of uncatalyzed cleavage to the mechanism occurring in ribozymes. This would contrast typical protein enzymes, primarily achieving catalysis by overall electrostatic effects in their catalytic center.

Název v anglickém jazyce

Mapping the Chemical Space of the RNA Cleavage and Its Implications for Ribozyme Catalysis

Popis výsledku anglicky

Ribozymes utilize diverse catalytic strategies. We report systematic quantum chemical calculations mapping the catalytic space of RNA cleavage by comparing all chemically feasible reaction mechanisms of RNA self-cleavage, using appropriate model systems including those chemical groups that may directly participate in ribozyme catalysis. We calculated the kinetics of uncatalyzed cleavage reactions proceeding via both monoanionic and dianionic pathways, and explicitly probed effects of various groups acting as general bases (GBs) and/or general acids (GAs), or electrostatic transition state stabilizers. In total, we explored 115 different mechanisms. The dianionic scenarios are generally preferred to monoanionic scenarios, although they may compete with one-another under some conditions. Direct GA catalysis seems to exert the dominant catalytic effect, while GB catalysis electrostatic stabilization are less efficient. Our results indirectly suggest that the dominant part of the catalytic effect might be explained by the shift of the reaction mechanism from the mechanism of uncatalyzed cleavage to the mechanism occurring in ribozymes. This would contrast typical protein enzymes, primarily achieving catalysis by overall electrostatic effects in their catalytic center.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Journal of Physical Chemistry B

ISSN

1520-6106

e-ISSN

—

Svazek periodika

121

Číslo periodika v rámci svazku

48

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

10828-10840

Kód UT WoS článku

000417672200010

EID výsledku v databázi Scopus

2-s2.0-85037727204