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prism.endingPage: 234
citation_title: Crystal structure of a DNA catalyst
WT.cg_s: Letter
access: Yes
keywords: X-ray crystallography, Nucleic acids
emanating: 134X76X223X157
citation_publisher: Nature Research
citation_journal_title: Nature
description: Catalysis in biology is restricted to RNA (ribozymes) and protein enzymes, but synthetic biomolecular catalysts can also be made of DNA (deoxyribozymes) or synthetic genetic polymers. In vitro selection from synthetic random DNA libraries identified DNA catalysts for various chemical reactions beyond RNA backbone cleavage. DNA-catalysed reactions include RNA and DNA ligation in various topologies, hydrolytic cleavage and photorepair of DNA, as well as reactions of peptides and small molecules. In spite of comprehensive biochemical studies of DNA catalysts for two decades, fundamental mechanistic understanding of their function is lacking in the absence of three-dimensional models at atomic resolution. Early attempts to solve the crystal structure of an RNA-cleaving deoxyribozyme resulted in a catalytically irrelevant nucleic acid fold. Here we report the crystal structure of the RNA-ligating deoxyribozyme 9DB1 (ref. 14) at 2.8?Å resolution. The structure captures the ligation reaction in the post-catalytic state, revealing a compact folding unit stabilized by numerous tertiary interactions, and an unanticipated organization of the catalytic centre. Structure-guided mutagenesis provided insights into the basis for regioselectivity of the ligation reaction and allowed remarkable manipulation of substrate recognition and reaction rate. Moreover, the structure highlights how the specific properties of deoxyribose are reflected in the backbone conformation of the DNA catalyst, in support of its intricate three-dimensional organization. The structural principles underlying the catalytic ability of DNA elucidate differences and similarities in DNA versus RNA catalysts, which is relevant for comprehending the privileged position of folded RNA in the prebiotic world and in current organisms.
WT.site_id: 18696
citation_date: 2016-01-14
title: Influence of 2?-modifications on mutant acceptor RNA U-1. : Crystal structure of a DNA catalyst : Nature : Nature Research
DC.title: Crystal structure of a DNA catalyst
DC.date: 2016-01-06
prism.issn: 0028-0836
DC.publisher: Nature Research
citation_online_date: 2016-01-06
WT.cg_n: Nature
DC.creator: Almudena Ponce-Salvatierra
prism.issue: 7585
DC.identifier: doi:10.1038/nature16471
dc:title: Influence of 2?-modifications on mutant acceptor RNA U-1. : Crystal structure of a DNA catalyst : Nature : Nature Research
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prism.publicationDate: 2016-01-06
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DC.rights: © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
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prism.rightsAgent: permissions@nature.com
citation_author: Almudena Ponce-Salvatierra
citation_issue: 7585
prism.eIssn: 1476-4687
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DC.language: en
prism.volume: 529
citation_firstpage: 231
prism.startingPage: 231
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prism.publicationName: Nature
citation_doi: doi:10.1038/nature16471
prism.section: Letter
citation_volume: 529
WT.site_id_name: Max Planck Inst for Biophysical Chemistry (Karl Friedrich Bonhoeffer Inst)
Content-Language: en
prism.copyright: © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.