Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F15%3A33156896" target="_blank" >RIV/61989592:15310/15:33156896 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/15:00457647 RIV/00216224:14740/15:00082900
Result on the web
<a href="http://pubs.rsc.org/en/content/articlehtml/2015/cp/c4cp05083e" target="_blank" >http://pubs.rsc.org/en/content/articlehtml/2015/cp/c4cp05083e</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1039/c4cp05083e" target="_blank" >10.1039/c4cp05083e</a>

Result language
angličtina
Original language name
Wobble pairs of the HDV ribozyme play specific roles in stabilization of active site dynamics
Original language description
The hepatitis delta virus (HDV) is the only known human pathogen whose genome contains a catalytic RNA motif (ribozyme). The overall architecture of the HDV ribozyme is that of a double-nested pseudoknot, with two GU pairs flanking the active site. Although extensive studies have shown that mutation of either wobble results in decreased catalytic activity, little work has focused on linking these mutations to specific structural effects on catalytic fitness. Here we use molecular dynamics simulations based on an activated structure to probe the active site dynamics as a result of wobble pair mutations. In both wild-type and mutant ribozymes, the in-line fitness of the active site (as a measure of catalytic proficiency) strongly depends on the presenceof a C75(N3H3+)N1(O5') hydrogen bond, which positions C75 as the general acid for the reaction. Our mutational analyses show that each GU wobble supports catalytically fit conformations in distinct ways; the reverse G25U20 wobble promotes
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CF - Physical chemistry and theoretical chemistry
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)

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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