A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches

In a previous work, it was shown that punicalagin, an active ingredient of pomegranate, is able to bind to PDIA3 and inhibit its disulfide reductase activity. Here we provide evidence that punicalagin can also bind to PDIA1, the main expressed form of protein disulfide isomerase (PDI). In this compa...

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Autores principales:	Giuliano Paglia, Lorenzo Antonini, Laura Cervoni, Rino Ragno, Manuela Sabatino, Marco Minacori, Elisabetta Rubini, Fabio Altieri
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	protein disulfide isomerase PDIA3/ERp57 inhibitor punicalagin molecular docking molecular dynamics Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/30b42938319c4b4d99f6cd2368178aca
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spelling	oai:doaj.org-article:30b42938319c4b4d99f6cd2368178aca2021-11-25T16:48:40ZA Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches10.3390/biomedicines91115332227-9059https://doaj.org/article/30b42938319c4b4d99f6cd2368178aca2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1533https://doaj.org/toc/2227-9059In a previous work, it was shown that punicalagin, an active ingredient of pomegranate, is able to bind to PDIA3 and inhibit its disulfide reductase activity. Here we provide evidence that punicalagin can also bind to PDIA1, the main expressed form of protein disulfide isomerase (PDI). In this comparative study, the affinity and the effect of punicalagin binding on each protein were evaluated, and a computational approach was used to identify putative binding sites. Punicalagin binds to either PDIA1 or PDIA3 with a similar affinity, but the inhibition efficacy on protein reductase activity is higher for PDIA3. Additionally, punicalagin differently affects the thermal denaturation profile of both proteins. Molecular docking and molecular dynamics simulations led to propose a punicalagin binding mode on PDIA1 and PDIA3, identifying the binding sites at the redox domains <i>a’</i> in two different pockets, suggesting different effects of punicalagin on proteins’ structure. This study provides insights to develop punicalagin-based ligands, to set up a rational design for PDIA3 selective inhibitors, and to dissect the molecular determinant to modulate the protein activity.Giuliano PagliaLorenzo AntoniniLaura CervoniRino RagnoManuela SabatinoMarco MinacoriElisabetta RubiniFabio AltieriMDPI AGarticleprotein disulfide isomerasePDIA3/ERp57inhibitorpunicalaginmolecular dockingmolecular dynamicsBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1533, p 1533 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	protein disulfide isomerase PDIA3/ERp57 inhibitor punicalagin molecular docking molecular dynamics Biology (General) QH301-705.5
spellingShingle	protein disulfide isomerase PDIA3/ERp57 inhibitor punicalagin molecular docking molecular dynamics Biology (General) QH301-705.5 Giuliano Paglia Lorenzo Antonini Laura Cervoni Rino Ragno Manuela Sabatino Marco Minacori Elisabetta Rubini Fabio Altieri A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches
description	In a previous work, it was shown that punicalagin, an active ingredient of pomegranate, is able to bind to PDIA3 and inhibit its disulfide reductase activity. Here we provide evidence that punicalagin can also bind to PDIA1, the main expressed form of protein disulfide isomerase (PDI). In this comparative study, the affinity and the effect of punicalagin binding on each protein were evaluated, and a computational approach was used to identify putative binding sites. Punicalagin binds to either PDIA1 or PDIA3 with a similar affinity, but the inhibition efficacy on protein reductase activity is higher for PDIA3. Additionally, punicalagin differently affects the thermal denaturation profile of both proteins. Molecular docking and molecular dynamics simulations led to propose a punicalagin binding mode on PDIA1 and PDIA3, identifying the binding sites at the redox domains <i>a’</i> in two different pockets, suggesting different effects of punicalagin on proteins’ structure. This study provides insights to develop punicalagin-based ligands, to set up a rational design for PDIA3 selective inhibitors, and to dissect the molecular determinant to modulate the protein activity.
format	article
author	Giuliano Paglia Lorenzo Antonini Laura Cervoni Rino Ragno Manuela Sabatino Marco Minacori Elisabetta Rubini Fabio Altieri
author_facet	Giuliano Paglia Lorenzo Antonini Laura Cervoni Rino Ragno Manuela Sabatino Marco Minacori Elisabetta Rubini Fabio Altieri
author_sort	Giuliano Paglia
title	A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches
title_short	A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches
title_full	A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches
title_fullStr	A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches
title_full_unstemmed	A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches
title_sort	comparative analysis of punicalagin interaction with pdia1 and pdia3 by biochemical and computational approaches
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/30b42938319c4b4d99f6cd2368178aca
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A Comparative Analysis of Punicalagin Interaction with PDIA1 and PDIA3 by Biochemical and Computational Approaches

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