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Design of a colicin E7 based chimeric zinc-finger nuclease
Colicin E7 is a natural bacterial toxin. Its nuclease domain (NColE7) enters the target cell and kills it by digesting the nucleic acids. The HNH-motif as the catalytic centre of NColE7 at the C-terminus requires the positively charged N-terminal loop for the nuclease activity—offering opportunities...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104000/ https://www.ncbi.nlm.nih.gov/pubmed/24952471 http://dx.doi.org/10.1007/s10822-014-9765-8 |
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author | Németh, Eszter Schilli, Gabriella K. Nagy, Gábor Hasenhindl, Christoph Gyurcsik, Béla Oostenbrink, Chris |
author_facet | Németh, Eszter Schilli, Gabriella K. Nagy, Gábor Hasenhindl, Christoph Gyurcsik, Béla Oostenbrink, Chris |
author_sort | Németh, Eszter |
collection | PubMed |
description | Colicin E7 is a natural bacterial toxin. Its nuclease domain (NColE7) enters the target cell and kills it by digesting the nucleic acids. The HNH-motif as the catalytic centre of NColE7 at the C-terminus requires the positively charged N-terminal loop for the nuclease activity—offering opportunities for allosteric control in a NColE7-based artificial nuclease. Accordingly, four novel zinc finger nucleases were designed by computational methods exploiting the special structural features of NColE7. The constructed models were subjected to MD simulations. The comparison of structural stability and functional aspects showed that these models may function as safely controlled artificial nucleases. This study was complemented by random mutagenesis experiments identifying potentially important residues for NColE7 function outside the catalytic region. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10822-014-9765-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4104000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-41040002014-07-21 Design of a colicin E7 based chimeric zinc-finger nuclease Németh, Eszter Schilli, Gabriella K. Nagy, Gábor Hasenhindl, Christoph Gyurcsik, Béla Oostenbrink, Chris J Comput Aided Mol Des Article Colicin E7 is a natural bacterial toxin. Its nuclease domain (NColE7) enters the target cell and kills it by digesting the nucleic acids. The HNH-motif as the catalytic centre of NColE7 at the C-terminus requires the positively charged N-terminal loop for the nuclease activity—offering opportunities for allosteric control in a NColE7-based artificial nuclease. Accordingly, four novel zinc finger nucleases were designed by computational methods exploiting the special structural features of NColE7. The constructed models were subjected to MD simulations. The comparison of structural stability and functional aspects showed that these models may function as safely controlled artificial nucleases. This study was complemented by random mutagenesis experiments identifying potentially important residues for NColE7 function outside the catalytic region. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10822-014-9765-8) contains supplementary material, which is available to authorized users. Springer International Publishing 2014-06-22 2014 /pmc/articles/PMC4104000/ /pubmed/24952471 http://dx.doi.org/10.1007/s10822-014-9765-8 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Article Németh, Eszter Schilli, Gabriella K. Nagy, Gábor Hasenhindl, Christoph Gyurcsik, Béla Oostenbrink, Chris Design of a colicin E7 based chimeric zinc-finger nuclease |
title | Design of a colicin E7 based chimeric zinc-finger nuclease |
title_full | Design of a colicin E7 based chimeric zinc-finger nuclease |
title_fullStr | Design of a colicin E7 based chimeric zinc-finger nuclease |
title_full_unstemmed | Design of a colicin E7 based chimeric zinc-finger nuclease |
title_short | Design of a colicin E7 based chimeric zinc-finger nuclease |
title_sort | design of a colicin e7 based chimeric zinc-finger nuclease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104000/ https://www.ncbi.nlm.nih.gov/pubmed/24952471 http://dx.doi.org/10.1007/s10822-014-9765-8 |
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