Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation

Abstract Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA-cleaving 10-23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the re...

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Main Authors: Evan R. Cramer, Sarah A. Starcovic, Rebekah M. Avey, Ali I. Kaya, Aaron R. Robart
Format: Article
Language:English
Published: Nature Portfolio 2023-06-01
Series:Communications Chemistry
Online Access:https://doi.org/10.1038/s42004-023-00924-3
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author Evan R. Cramer
Sarah A. Starcovic
Rebekah M. Avey
Ali I. Kaya
Aaron R. Robart
author_facet Evan R. Cramer
Sarah A. Starcovic
Rebekah M. Avey
Ali I. Kaya
Aaron R. Robart
author_sort Evan R. Cramer
collection DOAJ
description Abstract Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA-cleaving 10-23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the recruitment of other components to cleave RNA and can turnover, thus they have a distinct advantage over other knockdown methods (siRNA, CRISPR, morpholinos). Despite this, a lack of structural and mechanistic information has hindered the optimization and application of the 10-23 DNAzyme. Here, we report a 2.7 Å crystal structure of the RNA-cleaving 10-23 DNAzyme in a homodimer conformation. Although proper coordination of the DNAzyme to substrate is observed along with intriguing patterns of bound magnesium ions, the dimer conformation likely does not capture the true catalytic form of the 10-23 DNAzyme.
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spelling doaj.art-580d77483d534dbcbed32b06bc3ea6b92023-06-11T11:07:43ZengNature PortfolioCommunications Chemistry2399-36692023-06-01611610.1038/s42004-023-00924-3Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformationEvan R. Cramer0Sarah A. Starcovic1Rebekah M. Avey2Ali I. Kaya3Aaron R. Robart4Department of Biochemistry and Molecular Medicine, West Virginia UniversityDepartment of Biochemistry and Molecular Medicine, West Virginia UniversityDepartment of Biochemistry and Molecular Medicine, West Virginia UniversityNE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Argonne National LaboratoryDepartment of Biochemistry and Molecular Medicine, West Virginia UniversityAbstract Deoxyribozymes (DNAzymes) are in vitro evolved DNA sequences capable of catalyzing chemical reactions. The RNA-cleaving 10-23 DNAzyme was the first DNAzyme to be evolved and possesses clinical and biotechnical applications as a biosensor and a knockdown agent. DNAzymes do not require the recruitment of other components to cleave RNA and can turnover, thus they have a distinct advantage over other knockdown methods (siRNA, CRISPR, morpholinos). Despite this, a lack of structural and mechanistic information has hindered the optimization and application of the 10-23 DNAzyme. Here, we report a 2.7 Å crystal structure of the RNA-cleaving 10-23 DNAzyme in a homodimer conformation. Although proper coordination of the DNAzyme to substrate is observed along with intriguing patterns of bound magnesium ions, the dimer conformation likely does not capture the true catalytic form of the 10-23 DNAzyme.https://doi.org/10.1038/s42004-023-00924-3
spellingShingle Evan R. Cramer
Sarah A. Starcovic
Rebekah M. Avey
Ali I. Kaya
Aaron R. Robart
Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation
Communications Chemistry
title Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation
title_full Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation
title_fullStr Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation
title_full_unstemmed Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation
title_short Structure of a 10-23 deoxyribozyme exhibiting a homodimer conformation
title_sort structure of a 10 23 deoxyribozyme exhibiting a homodimer conformation
url https://doi.org/10.1038/s42004-023-00924-3
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