The role of an active site Mg2+ in HDV ribozyme self-cleavage: insights from QM/MM calculations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F15%3A00442423" target="_blank" >RIV/68081707:_____/15:00442423 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/15:33156519 RIV/00216224:14740/15:00082202

Výsledek na webu

<a href="http://dx.doi.org/10.1039/c4cp03857f" target="_blank" >http://dx.doi.org/10.1039/c4cp03857f</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c4cp03857f" target="_blank" >10.1039/c4cp03857f</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The role of an active site Mg2+ in HDV ribozyme self-cleavage: insights from QM/MM calculations

Popis výsledku v původním jazyce

The hepatitis delta virus (HDV) ribozyme is a catalytic RNA motif embedded in the human pathogenic HDV RNA. It catalyzes self-cleavage of its sugar-phosphate backbone with direct participation of the active site cytosine C75. Biochemical and structural data support a general acid role of C75. Here, we used hybrid quantum mechanical/molecular mechanical (QM/MM) calculations to probe the reaction mechanism and changes in Gibbs energy along the ribozyme's reaction pathway with an N3-protonated C75H(+) in the active site, which acts as the general acid, and a partially hydrated Mg2+ ion with one deprotonated, inner-shell coordinated water molecule that acts as the general base. We followed eight reaction paths with a distinct position and coordination of the catalytically important active site Mg2+ ion. For six of them, we observed feasible activation barriers ranging from 14.2 to 21.9 kcal mol(-1), indicating that the specific position of the Mg2+ ion in the active site is predicted to st

Název v anglickém jazyce

The role of an active site Mg2+ in HDV ribozyme self-cleavage: insights from QM/MM calculations

Popis výsledku anglicky

The hepatitis delta virus (HDV) ribozyme is a catalytic RNA motif embedded in the human pathogenic HDV RNA. It catalyzes self-cleavage of its sugar-phosphate backbone with direct participation of the active site cytosine C75. Biochemical and structural data support a general acid role of C75. Here, we used hybrid quantum mechanical/molecular mechanical (QM/MM) calculations to probe the reaction mechanism and changes in Gibbs energy along the ribozyme's reaction pathway with an N3-protonated C75H(+) in the active site, which acts as the general acid, and a partially hydrated Mg2+ ion with one deprotonated, inner-shell coordinated water molecule that acts as the general base. We followed eight reaction paths with a distinct position and coordination of the catalytically important active site Mg2+ ion. For six of them, we observed feasible activation barriers ranging from 14.2 to 21.9 kcal mol(-1), indicating that the specific position of the Mg2+ ion in the active site is predicted to st

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

BO - Biofyzika

OECD FORD obor

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Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Physical Chemistry Chemical Physics

ISSN

1463-9076

e-ISSN

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Svazek periodika

17

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

670-679

Kód UT WoS článku

000346235600071

EID výsledku v databázi Scopus

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