Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782437291981012992 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4905666 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT panigiovanna naturalphenolicinhibitorsoftrichothecenebiosynthesisbythewheatfungalpathogenfusariumculmorumacomputationalinsightintothestructureactivityrelationship AT dessialessandro naturalphenolicinhibitorsoftrichothecenebiosynthesisbythewheatfungalpathogenfusariumculmorumacomputationalinsightintothestructureactivityrelationship AT dallocchioroberto naturalphenolicinhibitorsoftrichothecenebiosynthesisbythewheatfungalpathogenfusariumculmorumacomputationalinsightintothestructureactivityrelationship AT schermbarbara naturalphenolicinhibitorsoftrichothecenebiosynthesisbythewheatfungalpathogenfusariumculmorumacomputationalinsightintothestructureactivityrelationship AT azaraemanuela naturalphenolicinhibitorsoftrichothecenebiosynthesisbythewheatfungalpathogenfusariumculmorumacomputationalinsightintothestructureactivityrelationship AT delogugiovanna naturalphenolicinhibitorsoftrichothecenebiosynthesisbythewheatfungalpathogenfusariumculmorumacomputationalinsightintothestructureactivityrelationship AT migheliquirico naturalphenolicinhibitorsoftrichothecenebiosynthesisbythewheatfungalpathogenfusariumculmorumacomputationalinsightintothestructureactivityrelationship |