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@ARTICLE{Borggrfe:904599,
author = {Borggräfe, Jan and Victor, Julian and Rosenbach, Hannah
and Viegas, Aldino and Gertzen, Christoph G. W. and Wuebben,
Christine and Kovacs, Helena and Gopalswamy, Mohanraj and
Riesner, Detlev and Steger, Gerhard and Schiemann, Olav and
Gohlke, Holger and Span, Ingrid and Etzkorn, Manuel},
title = {{T}ime-resolved structural analysis of an {RNA}-cleaving
{DNA} catalyst},
journal = {Nature},
volume = {601},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publ. Group},
reportid = {FZJ-2021-06169},
pages = {144-149},
year = {2022},
abstract = {The 10–23 DNAzyme is one of the most prominent
catalytically active DNA sequences1,2. Its ability to cleave
a wide range of RNA targets with high selectivity entails a
substantial therapeutic and biotechnological potential2.
However, the high expectations have not yet been met, a fact
that coincides with the lack of high-resolution and
time-resolved information about its mode of action3. Here we
provide high-resolution NMR characterization of all apparent
states of the prototypic 10–23 DNAzyme and present a
comprehensive survey of the kinetics and dynamics of its
catalytic function. The determined structure and identified
metal-ion-binding sites of the precatalytic DNAzyme–RNA
complex reveal that the basis of the DNA-mediated catalysis
is an interplay among three factors: an unexpected, yet
exciting molecular architecture; distinct conformational
plasticity; and dynamic modulation by metal ions. We further
identify previously hidden rate-limiting transient
intermediate states in the DNA-mediated catalytic process
via real-time NMR measurements. Using a rationally selected
single-atom replacement, we could considerably enhance the
performance of the DNAzyme, demonstrating that the acquired
knowledge of the molecular structure, its plasticity and the
occurrence of long-lived intermediate states constitutes a
valuable starting point for the rational design of
next-generation DNAzymes.},
cin = {JSC / NIC / IBI-7 / IBG-4},
ddc = {500},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
I:(DE-Juel1)IBI-7-20200312 / I:(DE-Juel1)IBG-4-20200403},
pnm = {5111 - Domain-Specific Simulation $\&$ Data Life Cycle Labs
(SDLs) and Research Groups (POF4-511) / 2171 - Biological
and environmental resources for sustainable use (POF4-217) /
2172 - Utilization of renewable carbon and energy sources
and engineering of ecosystem functions (POF4-217) / 5244 -
Information Processing in Neuronal Networks (POF4-524) /
Forschergruppe Gohlke $(hkf7_20200501)$},
pid = {G:(DE-HGF)POF4-5111 / G:(DE-HGF)POF4-2171 /
G:(DE-HGF)POF4-2172 / G:(DE-HGF)POF4-5244 /
$G:(DE-Juel1)hkf7_20200501$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34949858},
UT = {WOS:000734154500001},
doi = {10.1038/s41586-021-04225-4},
url = {https://juser.fz-juelich.de/record/904599},
}