Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study

We have previously demonstrated that BaSpIIRP4 (an acidic PLA2 from Bothrops alternatus venom), enhance the endothelial cells (EC) detachment effect of a snake venom metalloproteinase. Considering that the binding of cells to their ligands depends on the interaction between extracellular matrix and...

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Autores principales: Angelina, Emilio Luis, Bustillo, Soledad, Bogado, María Lucrecia, García Denegri, María Emilia, Peruchena, Nélida María, Leiva, Laura Cristina Ana
Formato: Artículo
Lenguaje:Inglés
Publicado: Elsevier 2025
Materias:
Venom
Acidic
Snake
Acceso en línea:http://repositorio.unne.edu.ar/handle/123456789/56544
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RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE) de Universidad Nacional del Nordeste
id I48-R184-123456789-56544
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spelling I48-R184-123456789-565442025-04-28T13:32:36Z Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study Angelina, Emilio Luis Bustillo, Soledad Bogado, María Lucrecia García Denegri, María Emilia Peruchena, Nélida María Leiva, Laura Cristina Ana Venom Acidic Snake We have previously demonstrated that BaSpIIRP4 (an acidic PLA2 from Bothrops alternatus venom), enhance the endothelial cells (EC) detachment effect of a snake venom metalloproteinase. Considering that the binding of cells to their ligands depends on the interaction between extracellular matrix and integral membrane proteins, this effect may be due to interactions between PLA2 and EC integrins. The integrin alpha-v beta-3 (avb3) is commonly expressed in endothelial cells. It has been reported that human PLA2-IIA binds to this integrin with high affinity. Moreover, it was demonstrated that arginine residues R74 and R100 are critical for this binding. In addition, the interaction svPLA2-avb3 integrin was also described. Considering these previous findings about the interaction of human and snake venom PLA2-IIA with integrin avb3, in this work we use an in silico approach to predict whether BaSpIIRP4 would also bind to the same integrin, thus supporting the hypothesis that EC detachment could be a receptor-mediated effect. Since structure of BaSpIIRP4 PLA2 has not yet been elucidated, an enzyme homology model was built with the Modeller software. PLA2 from Bothrops jararacussu was selected as tem-plate structure. To identify putative sites on the surface of the PLA2 model with capacity to interact with the RGD site on the headpiece of the avb3 integrin, the protein-protein docking server ClusPro was employed. The stability of the identified anchoring points was evaluated by Molecular Dynamic simulations with Amber16 and binding free energy calculations with MM-PBSA protocol. Three interaction sites were found, one of them showing a strong resemblance with the previously identified site on hu- man PLA2-IIA. These results suggest that integrin avb3 may serve as receptor for PLA2 from B. alternatus venom, and this interaction could be a novel therapeutic target. 2025-04-25T14:12:01Z 2025-04-25T14:12:01Z 2020 Artículo Angelina, Emilio Luis, et al., 2020. Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study. Toxicon. San Diego: Elsevier, vol. 177, p. 52-52. E-ISSN 1879-3150. 0041-0101 http://repositorio.unne.edu.ar/handle/123456789/56544 eng https://www.sciencedirect.com/journal/toxicon closedAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ application/pdf p. 52-52 application/pdf Elsevier Toxicon, 2020, vol. 177, p. 52-52.
institution Universidad Nacional del Nordeste
institution_str I-48
repository_str R-184
collection RIUNNE - Repositorio Institucional de la Universidad Nacional del Nordeste (UNNE)
language Inglés
topic Venom
Acidic
Snake
spellingShingle Venom
Acidic
Snake
Angelina, Emilio Luis
Bustillo, Soledad
Bogado, María Lucrecia
García Denegri, María Emilia
Peruchena, Nélida María
Leiva, Laura Cristina Ana
Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study
topic_facet Venom
Acidic
Snake
description We have previously demonstrated that BaSpIIRP4 (an acidic PLA2 from Bothrops alternatus venom), enhance the endothelial cells (EC) detachment effect of a snake venom metalloproteinase. Considering that the binding of cells to their ligands depends on the interaction between extracellular matrix and integral membrane proteins, this effect may be due to interactions between PLA2 and EC integrins. The integrin alpha-v beta-3 (avb3) is commonly expressed in endothelial cells. It has been reported that human PLA2-IIA binds to this integrin with high affinity. Moreover, it was demonstrated that arginine residues R74 and R100 are critical for this binding. In addition, the interaction svPLA2-avb3 integrin was also described. Considering these previous findings about the interaction of human and snake venom PLA2-IIA with integrin avb3, in this work we use an in silico approach to predict whether BaSpIIRP4 would also bind to the same integrin, thus supporting the hypothesis that EC detachment could be a receptor-mediated effect. Since structure of BaSpIIRP4 PLA2 has not yet been elucidated, an enzyme homology model was built with the Modeller software. PLA2 from Bothrops jararacussu was selected as tem-plate structure. To identify putative sites on the surface of the PLA2 model with capacity to interact with the RGD site on the headpiece of the avb3 integrin, the protein-protein docking server ClusPro was employed. The stability of the identified anchoring points was evaluated by Molecular Dynamic simulations with Amber16 and binding free energy calculations with MM-PBSA protocol. Three interaction sites were found, one of them showing a strong resemblance with the previously identified site on hu- man PLA2-IIA. These results suggest that integrin avb3 may serve as receptor for PLA2 from B. alternatus venom, and this interaction could be a novel therapeutic target.
format Artículo
author Angelina, Emilio Luis
Bustillo, Soledad
Bogado, María Lucrecia
García Denegri, María Emilia
Peruchena, Nélida María
Leiva, Laura Cristina Ana
author_facet Angelina, Emilio Luis
Bustillo, Soledad
Bogado, María Lucrecia
García Denegri, María Emilia
Peruchena, Nélida María
Leiva, Laura Cristina Ana
author_sort Angelina, Emilio Luis
title Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study
title_short Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study
title_full Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study
title_fullStr Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study
title_full_unstemmed Binding of acidic PLA2 Ba SPII RP4 from Bothrops Alternatus snake venom to integrin avb3 : an in silico study
title_sort binding of acidic pla2 ba spii rp4 from bothrops alternatus snake venom to integrin avb3 : an in silico study
publisher Elsevier
publishDate 2025
url http://repositorio.unne.edu.ar/handle/123456789/56544
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