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Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin

It has been reported that Paulistine in the venom of the wasp Polybia paulista co-exists as two different forms: an oxidized form presenting a compact structure due to the presence of a disulfide bridge, which causes inflammation through an apparent interaction with receptors in the 5-lipoxygenase p...

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Autores principales: Arcuri, Helen Andrade, Gomes, Paulo Cesar, de Souza, Bibiana Monson, Dias, Nathalia Baptista, Brigatte, Patrícia, Stabeli, Rodrigo Guerino, Palma, Mario Sergio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810206/
https://www.ncbi.nlm.nih.gov/pubmed/26938560
http://dx.doi.org/10.3390/toxins8030061
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author Arcuri, Helen Andrade
Gomes, Paulo Cesar
de Souza, Bibiana Monson
Dias, Nathalia Baptista
Brigatte, Patrícia
Stabeli, Rodrigo Guerino
Palma, Mario Sergio
author_facet Arcuri, Helen Andrade
Gomes, Paulo Cesar
de Souza, Bibiana Monson
Dias, Nathalia Baptista
Brigatte, Patrícia
Stabeli, Rodrigo Guerino
Palma, Mario Sergio
author_sort Arcuri, Helen Andrade
collection PubMed
description It has been reported that Paulistine in the venom of the wasp Polybia paulista co-exists as two different forms: an oxidized form presenting a compact structure due to the presence of a disulfide bridge, which causes inflammation through an apparent interaction with receptors in the 5-lipoxygenase pathway, and a naturally reduced form (without the disulfide bridge) that exists in a linear conformation and which also causes hyperalgesia and acts in the cyclooxygenase type II pathway. The reduced peptide was acetamidomethylated (Acm-Paulistine) to stabilize this form, and it still maintained its typical inflammatory activity. Oxidized Paulistine docks onto PGHS2 (COX-2) molecules, blocking the access of oxygen to the heme group and inhibiting the inflammatory activity of Acm-Paulistine in the cyclooxygenase type II pathway. Docking simulations revealed that the site of the docking of Paulistine within the PGHS2 molecule is unusual among commercial inhibitors of the enzyme, with an affinity potentially much higher than those observed for traditional anti-inflammatory drugs. Therefore, Paulistine causes inflammatory activity at the level of the 5-lipooxygenase pathway and, in parallel, it competes with its reduced form in relation to the activation of the cyclooxygenase pathway. Thus, while the reduced Paulistine causes inflammation, its oxidized form is a potent inhibitor of this activity.
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spelling pubmed-48102062016-04-04 Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin Arcuri, Helen Andrade Gomes, Paulo Cesar de Souza, Bibiana Monson Dias, Nathalia Baptista Brigatte, Patrícia Stabeli, Rodrigo Guerino Palma, Mario Sergio Toxins (Basel) Article It has been reported that Paulistine in the venom of the wasp Polybia paulista co-exists as two different forms: an oxidized form presenting a compact structure due to the presence of a disulfide bridge, which causes inflammation through an apparent interaction with receptors in the 5-lipoxygenase pathway, and a naturally reduced form (without the disulfide bridge) that exists in a linear conformation and which also causes hyperalgesia and acts in the cyclooxygenase type II pathway. The reduced peptide was acetamidomethylated (Acm-Paulistine) to stabilize this form, and it still maintained its typical inflammatory activity. Oxidized Paulistine docks onto PGHS2 (COX-2) molecules, blocking the access of oxygen to the heme group and inhibiting the inflammatory activity of Acm-Paulistine in the cyclooxygenase type II pathway. Docking simulations revealed that the site of the docking of Paulistine within the PGHS2 molecule is unusual among commercial inhibitors of the enzyme, with an affinity potentially much higher than those observed for traditional anti-inflammatory drugs. Therefore, Paulistine causes inflammatory activity at the level of the 5-lipooxygenase pathway and, in parallel, it competes with its reduced form in relation to the activation of the cyclooxygenase pathway. Thus, while the reduced Paulistine causes inflammation, its oxidized form is a potent inhibitor of this activity. MDPI 2016-02-29 /pmc/articles/PMC4810206/ /pubmed/26938560 http://dx.doi.org/10.3390/toxins8030061 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arcuri, Helen Andrade
Gomes, Paulo Cesar
de Souza, Bibiana Monson
Dias, Nathalia Baptista
Brigatte, Patrícia
Stabeli, Rodrigo Guerino
Palma, Mario Sergio
Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin
title Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin
title_full Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin
title_fullStr Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin
title_full_unstemmed Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin
title_short Paulistine—The Functional Duality of a Wasp Venom Peptide Toxin
title_sort paulistine—the functional duality of a wasp venom peptide toxin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810206/
https://www.ncbi.nlm.nih.gov/pubmed/26938560
http://dx.doi.org/10.3390/toxins8030061
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