Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates

Detalhes bibliográficos
Autor(a) principal: Chaves-Moreira, Daniele
Data de Publicação: 2023
Outros Autores: Gremski, Luiza Helena, de Moraes, Fábio Rogério [UNESP], Vuitika, Larissa, Wille, Ana Carolina Martins, Hernández González, Jorge Enrique [UNESP], Chaim, Olga Meiri, Senff-Ribeiro, Andrea, Arni, Raghuvir Krishnaswamy [UNESP], Veiga, Silvio Sanches
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3390/toxins15020109
http://hdl.handle.net/11449/249715
Resumo: Brown spider envenomation results in dermonecrosis, characterized by an intense inflammatory reaction. The principal toxins of brown spider venoms are phospholipase-D isoforms, which interact with different cellular membrane components, degrade phospholipids, and generate bioactive mediators leading to harmful effects. The Loxosceles intermedia phospholipase D, LiRecDT1, possesses a loop that modulates the accessibility to the active site and plays a crucial role in substrate. In vitro and in silico analyses were performed to determine aspects of this enzyme’s substrate preference. Sphingomyelin d18:1/6:0 was the preferred substrate of LiRecDT1 compared to other Sphingomyelins. Lysophosphatidylcholine 16:0/0:0 was preferred among other lysophosphatidylcholines, but much less than Sphingomyelin d18:1/6:0. In contrast, phosphatidylcholine d18:1/16:0 was not cleaved. Thus, the number of carbon atoms in the substrate plays a vital role in determining the optimal activity of this phospholipase-D. The presence of an amide group at C2 plays a key role in recognition and activity. In silico analyses indicated that a subsite containing the aromatic residues Y228 and W230 appears essential for choline recognition by cation-π interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms.
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spelling Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substratesbrown spiderLoxosceles intermediaphospholipase-D substratephospholipidsrecombinant toxinvenomBrown spider envenomation results in dermonecrosis, characterized by an intense inflammatory reaction. The principal toxins of brown spider venoms are phospholipase-D isoforms, which interact with different cellular membrane components, degrade phospholipids, and generate bioactive mediators leading to harmful effects. The Loxosceles intermedia phospholipase D, LiRecDT1, possesses a loop that modulates the accessibility to the active site and plays a crucial role in substrate. In vitro and in silico analyses were performed to determine aspects of this enzyme’s substrate preference. Sphingomyelin d18:1/6:0 was the preferred substrate of LiRecDT1 compared to other Sphingomyelins. Lysophosphatidylcholine 16:0/0:0 was preferred among other lysophosphatidylcholines, but much less than Sphingomyelin d18:1/6:0. In contrast, phosphatidylcholine d18:1/16:0 was not cleaved. Thus, the number of carbon atoms in the substrate plays a vital role in determining the optimal activity of this phospholipase-D. The presence of an amide group at C2 plays a key role in recognition and activity. In silico analyses indicated that a subsite containing the aromatic residues Y228 and W230 appears essential for choline recognition by cation-π interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms.Department of Cell Biology Federal University of Paraná (UFPR)Department of Physics Multi-User Center for Biomolecular Innovation State University of São Paulo (UNESP)Department of Structural and Molecular Biology State University of Ponta Grossa (UEPG)Department of Pharmacology University of California San Diego, La JollaDepartment of Physics Multi-User Center for Biomolecular Innovation State University of São Paulo (UNESP)Universidade Federal do Paraná (UFPR)Universidade Estadual Paulista (UNESP)Universidade Estadual de Ponta Grossa (UEPG)University of California San DiegoChaves-Moreira, DanieleGremski, Luiza Helenade Moraes, Fábio Rogério [UNESP]Vuitika, LarissaWille, Ana Carolina MartinsHernández González, Jorge Enrique [UNESP]Chaim, Olga MeiriSenff-Ribeiro, AndreaArni, Raghuvir Krishnaswamy [UNESP]Veiga, Silvio Sanches2023-07-29T16:07:18Z2023-07-29T16:07:18Z2023-02-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/toxins15020109Toxins, v. 15, n. 2, 2023.2072-6651http://hdl.handle.net/11449/24971510.3390/toxins150201092-s2.0-85149197149Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengToxinsinfo:eu-repo/semantics/openAccess2023-07-29T16:07:18Zoai:repositorio.unesp.br:11449/249715Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:07:52.032677Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
title Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
spellingShingle Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
Chaves-Moreira, Daniele
brown spider
Loxosceles intermedia
phospholipase-D substrate
phospholipids
recombinant toxin
venom
title_short Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
title_full Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
title_fullStr Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
title_full_unstemmed Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
title_sort Brown Spider Venom Phospholipase-D Activity upon Different Lipid Substrates
author Chaves-Moreira, Daniele
author_facet Chaves-Moreira, Daniele
Gremski, Luiza Helena
de Moraes, Fábio Rogério [UNESP]
Vuitika, Larissa
Wille, Ana Carolina Martins
Hernández González, Jorge Enrique [UNESP]
Chaim, Olga Meiri
Senff-Ribeiro, Andrea
Arni, Raghuvir Krishnaswamy [UNESP]
Veiga, Silvio Sanches
author_role author
author2 Gremski, Luiza Helena
de Moraes, Fábio Rogério [UNESP]
Vuitika, Larissa
Wille, Ana Carolina Martins
Hernández González, Jorge Enrique [UNESP]
Chaim, Olga Meiri
Senff-Ribeiro, Andrea
Arni, Raghuvir Krishnaswamy [UNESP]
Veiga, Silvio Sanches
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Federal do Paraná (UFPR)
Universidade Estadual Paulista (UNESP)
Universidade Estadual de Ponta Grossa (UEPG)
University of California San Diego
dc.contributor.author.fl_str_mv Chaves-Moreira, Daniele
Gremski, Luiza Helena
de Moraes, Fábio Rogério [UNESP]
Vuitika, Larissa
Wille, Ana Carolina Martins
Hernández González, Jorge Enrique [UNESP]
Chaim, Olga Meiri
Senff-Ribeiro, Andrea
Arni, Raghuvir Krishnaswamy [UNESP]
Veiga, Silvio Sanches
dc.subject.por.fl_str_mv brown spider
Loxosceles intermedia
phospholipase-D substrate
phospholipids
recombinant toxin
venom
topic brown spider
Loxosceles intermedia
phospholipase-D substrate
phospholipids
recombinant toxin
venom
description Brown spider envenomation results in dermonecrosis, characterized by an intense inflammatory reaction. The principal toxins of brown spider venoms are phospholipase-D isoforms, which interact with different cellular membrane components, degrade phospholipids, and generate bioactive mediators leading to harmful effects. The Loxosceles intermedia phospholipase D, LiRecDT1, possesses a loop that modulates the accessibility to the active site and plays a crucial role in substrate. In vitro and in silico analyses were performed to determine aspects of this enzyme’s substrate preference. Sphingomyelin d18:1/6:0 was the preferred substrate of LiRecDT1 compared to other Sphingomyelins. Lysophosphatidylcholine 16:0/0:0 was preferred among other lysophosphatidylcholines, but much less than Sphingomyelin d18:1/6:0. In contrast, phosphatidylcholine d18:1/16:0 was not cleaved. Thus, the number of carbon atoms in the substrate plays a vital role in determining the optimal activity of this phospholipase-D. The presence of an amide group at C2 plays a key role in recognition and activity. In silico analyses indicated that a subsite containing the aromatic residues Y228 and W230 appears essential for choline recognition by cation-π interactions. These findings may help to explain why different cells, with different phospholipid fatty acid compositions exhibit distinct susceptibilities to brown spider venoms.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T16:07:18Z
2023-07-29T16:07:18Z
2023-02-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3390/toxins15020109
Toxins, v. 15, n. 2, 2023.
2072-6651
http://hdl.handle.net/11449/249715
10.3390/toxins15020109
2-s2.0-85149197149
url http://dx.doi.org/10.3390/toxins15020109
http://hdl.handle.net/11449/249715
identifier_str_mv Toxins, v. 15, n. 2, 2023.
2072-6651
10.3390/toxins15020109
2-s2.0-85149197149
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Toxins
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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