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Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis
Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C–C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are ca...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162201/ https://www.ncbi.nlm.nih.gov/pubmed/30266969 http://dx.doi.org/10.1038/s41467-018-06325-8 |
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author | Driller, Ronja Janke, Sophie Fuchs, Monika Warner, Evelyn Mhashal, Anil R. Major, Dan Thomas Christmann, Mathias Brück, Thomas Loll, Bernhard |
author_facet | Driller, Ronja Janke, Sophie Fuchs, Monika Warner, Evelyn Mhashal, Anil R. Major, Dan Thomas Christmann, Mathias Brück, Thomas Loll, Bernhard |
author_sort | Driller, Ronja |
collection | PubMed |
description | Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C–C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins’ structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2’s catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis. |
format | Online Article Text |
id | pubmed-6162201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61622012018-10-01 Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis Driller, Ronja Janke, Sophie Fuchs, Monika Warner, Evelyn Mhashal, Anil R. Major, Dan Thomas Christmann, Mathias Brück, Thomas Loll, Bernhard Nat Commun Article Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C–C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins’ structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2’s catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis. Nature Publishing Group UK 2018-09-28 /pmc/articles/PMC6162201/ /pubmed/30266969 http://dx.doi.org/10.1038/s41467-018-06325-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Driller, Ronja Janke, Sophie Fuchs, Monika Warner, Evelyn Mhashal, Anil R. Major, Dan Thomas Christmann, Mathias Brück, Thomas Loll, Bernhard Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis |
title | Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis |
title_full | Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis |
title_fullStr | Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis |
title_full_unstemmed | Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis |
title_short | Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis |
title_sort | towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162201/ https://www.ncbi.nlm.nih.gov/pubmed/30266969 http://dx.doi.org/10.1038/s41467-018-06325-8 |
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