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Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship

A model of the trichodiene synthase (TRI5) of the wheat fungal pathogen and type-B trichothecene producer Fusarium culmorum was developed based on homology modelling with the crystallized protein of F. sporotrichioides. Eight phenolic molecules, namely ferulic acid 1, apocynin 2, propyl gallate 3, e...

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Autores principales: Pani, Giovanna, Dessì, Alessandro, Dallocchio, Roberto, Scherm, Barbara, Azara, Emanuela, Delogu, Giovanna, Migheli, Quirico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905666/
https://www.ncbi.nlm.nih.gov/pubmed/27294666
http://dx.doi.org/10.1371/journal.pone.0157316
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author Pani, Giovanna
Dessì, Alessandro
Dallocchio, Roberto
Scherm, Barbara
Azara, Emanuela
Delogu, Giovanna
Migheli, Quirico
author_facet Pani, Giovanna
Dessì, Alessandro
Dallocchio, Roberto
Scherm, Barbara
Azara, Emanuela
Delogu, Giovanna
Migheli, Quirico
author_sort Pani, Giovanna
collection PubMed
description A model of the trichodiene synthase (TRI5) of the wheat fungal pathogen and type-B trichothecene producer Fusarium culmorum was developed based on homology modelling with the crystallized protein of F. sporotrichioides. Eight phenolic molecules, namely ferulic acid 1, apocynin 2, propyl gallate 3, eugenol 4, Me-dehydrozingerone 5, eugenol dimer 6, magnolol 7, and ellagic acid 8, were selected for their ability to inhibit trichothecene production and/or fungal vegetative growth in F. culmorum. The chemical structures of phenols were constructed and partially optimised based on Molecular Mechanics (MM) studies and energy minimisation by Density Functional Theory (DFT). Docking analysis of the phenolic molecules was run on the 3D model of F. culmorum TRI5. Experimental biological activity, molecular descriptors and interacting-structures obtained from computational analysis were compared. Besides the catalytic domain, three privileged sites in the interaction with the inhibitory molecules were identified on the protein surface. The TRI5-ligand interactions highlighted in this study represent a powerful tool to the identification of new Fusarium-targeted molecules with potential as trichothecene inhibitors.
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spelling pubmed-49056662016-06-28 Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship Pani, Giovanna Dessì, Alessandro Dallocchio, Roberto Scherm, Barbara Azara, Emanuela Delogu, Giovanna Migheli, Quirico PLoS One Research Article A model of the trichodiene synthase (TRI5) of the wheat fungal pathogen and type-B trichothecene producer Fusarium culmorum was developed based on homology modelling with the crystallized protein of F. sporotrichioides. Eight phenolic molecules, namely ferulic acid 1, apocynin 2, propyl gallate 3, eugenol 4, Me-dehydrozingerone 5, eugenol dimer 6, magnolol 7, and ellagic acid 8, were selected for their ability to inhibit trichothecene production and/or fungal vegetative growth in F. culmorum. The chemical structures of phenols were constructed and partially optimised based on Molecular Mechanics (MM) studies and energy minimisation by Density Functional Theory (DFT). Docking analysis of the phenolic molecules was run on the 3D model of F. culmorum TRI5. Experimental biological activity, molecular descriptors and interacting-structures obtained from computational analysis were compared. Besides the catalytic domain, three privileged sites in the interaction with the inhibitory molecules were identified on the protein surface. The TRI5-ligand interactions highlighted in this study represent a powerful tool to the identification of new Fusarium-targeted molecules with potential as trichothecene inhibitors. Public Library of Science 2016-06-13 /pmc/articles/PMC4905666/ /pubmed/27294666 http://dx.doi.org/10.1371/journal.pone.0157316 Text en © 2016 Pani et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Pani, Giovanna
Dessì, Alessandro
Dallocchio, Roberto
Scherm, Barbara
Azara, Emanuela
Delogu, Giovanna
Migheli, Quirico
Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship
title Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship
title_full Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship
title_fullStr Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship
title_full_unstemmed Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship
title_short Natural Phenolic Inhibitors of Trichothecene Biosynthesis by the Wheat Fungal Pathogen Fusarium culmorum: A Computational Insight into the Structure-Activity Relationship
title_sort natural phenolic inhibitors of trichothecene biosynthesis by the wheat fungal pathogen fusarium culmorum: a computational insight into the structure-activity relationship
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905666/
https://www.ncbi.nlm.nih.gov/pubmed/27294666
http://dx.doi.org/10.1371/journal.pone.0157316
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