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Structure of a 10–23 Deoxyribozyme Exhibiting a Homodimer Conformation

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...

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Autores principales: Cramer, Evan, Starcovic, Sarah, Avey, Rebekah, Kaya, Ali, Robart, Aaron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Journal Experts 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312968/
https://www.ncbi.nlm.nih.gov/pubmed/37398199
http://dx.doi.org/10.21203/rs.3.rs-2252941/v1
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author Cramer, Evan
Starcovic, Sarah
Avey, Rebekah
Kaya, Ali
Robart, Aaron
author_facet Cramer, Evan
Starcovic, Sarah
Avey, Rebekah
Kaya, Ali
Robart, Aaron
author_sort Cramer, Evan
collection PubMed
description 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 pubmed-103129682023-07-01 Structure of a 10–23 Deoxyribozyme Exhibiting a Homodimer Conformation Cramer, Evan Starcovic, Sarah Avey, Rebekah Kaya, Ali Robart, Aaron Res Sq Article 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. American Journal Experts 2023-05-31 /pmc/articles/PMC10312968/ /pubmed/37398199 http://dx.doi.org/10.21203/rs.3.rs-2252941/v1 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Cramer, Evan
Starcovic, Sarah
Avey, Rebekah
Kaya, Ali
Robart, Aaron
Structure of a 10–23 Deoxyribozyme Exhibiting a Homodimer Conformation
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312968/
https://www.ncbi.nlm.nih.gov/pubmed/37398199
http://dx.doi.org/10.21203/rs.3.rs-2252941/v1
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