Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis

Detalhes bibliográficos
Autor(a) principal: Borges, Rafael J. [UNESP]
Data de Publicação: 2023
Outros Autores: Cardoso, Fábio F. [UNESP], de Carvalho, Cicilia [UNESP], de Marino, Ivan, Pereira, Paulo S., Soares, Andreimar M., Dal-Pai-Silva, Maeli [UNESP], Usón, Isabel, Fontes, Marcos R.M. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.biochi.2022.10.011
http://hdl.handle.net/11449/246209
Resumo: Snake envenomation is an ongoing global health problem and tropical neglected disease that afflicts millions of people each year. The only specific treatment, antivenom, has several limitations that affects its proper distribution to the victims and its efficacy against local effects, such as myonecrosis. The main responsible for this consequence are the phospholipases A2 (PLA2) and PLA2-like proteins, such as BthTX-I from Bothrops jararacussu. Folk medicine resorts to plants such as Tabernaemontana catharinensis to palliate these and other snakebite effects. Here, we evaluated the effect of its root bark extract and one of its isolated compounds, 12-methoxy-4-methyl-voachalotine (MMV), against the in vitro paralysis and muscle damage induced by BthTX-I. Secondary and quaternary structures of BthTX-I were not modified by the interaction with MMV. Instead, this compound interacted in an unprecedented way with the region inside the toxin hydrophobic channel and promoted a structural change in Val31, loop 58–71 and Membrane Disruption Site. Thus, we hypothesize that MMV inhibits PLA2-like proteins by preventing entrance of fatty acid into the hydrophobic channel. These data may explain the traditional use of T. catharinensis extract and confirm MMV as a promising candidate to complement antivenom or a structural guide to develop more effective inhibitors.
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spelling Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensisMMVMyotoxic inhibitorPLA2-Like proteinsSnake venomTabernaemontana catharinensisSnake envenomation is an ongoing global health problem and tropical neglected disease that afflicts millions of people each year. The only specific treatment, antivenom, has several limitations that affects its proper distribution to the victims and its efficacy against local effects, such as myonecrosis. The main responsible for this consequence are the phospholipases A2 (PLA2) and PLA2-like proteins, such as BthTX-I from Bothrops jararacussu. Folk medicine resorts to plants such as Tabernaemontana catharinensis to palliate these and other snakebite effects. Here, we evaluated the effect of its root bark extract and one of its isolated compounds, 12-methoxy-4-methyl-voachalotine (MMV), against the in vitro paralysis and muscle damage induced by BthTX-I. Secondary and quaternary structures of BthTX-I were not modified by the interaction with MMV. Instead, this compound interacted in an unprecedented way with the region inside the toxin hydrophobic channel and promoted a structural change in Val31, loop 58–71 and Membrane Disruption Site. Thus, we hypothesize that MMV inhibits PLA2-like proteins by preventing entrance of fatty acid into the hydrophobic channel. These data may explain the traditional use of T. catharinensis extract and confirm MMV as a promising candidate to complement antivenom or a structural guide to develop more effective inhibitors.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Federación Española de Enfermedades RarasMinisterio de Ciencia e InnovaciónUniversity of the EastFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Pennsylvania Game CommissionDepartamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP), São PauloCrystallographic Methods Institute of Molecular Biology of Barcelona (IBMB-CSIC)Instituto Federal de Goiás (IF-GO), GoiásLaboratório de Biotecnologia de Proteínas e Compostos Bioativos Aplicados à Saúde Fundação Oswaldo Cruz (FIOCRUZ) Unidade Rondônia, RODepartamento de Biologia Estrutural e Funcional Instituto de Biociências Universidade Estadual Paulista (UNESP), São PauloICREA Institució Catalana de Recerca i Estudis Avançats Passeig Lluís Companys, 23, Barcelona, E-08003, SpainDepartamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP), São PauloDepartamento de Biologia Estrutural e Funcional Instituto de Biociências Universidade Estadual Paulista (UNESP), São PauloFAPESP: 2016/24191-8FAPESP: 2019/05958-4FAPESP: 2020/10143-7FAPESP: 2021/01463-0CNPq: 302643/2021-4Pennsylvania Game Commission: PGC2018-101370-BI00Universidade Estadual Paulista (UNESP)Institute of Molecular Biology of Barcelona (IBMB-CSIC)Instituto Federal de Goiás (IF-GO)Unidade RondôniaPasseig Lluís CompanysBorges, Rafael J. [UNESP]Cardoso, Fábio F. [UNESP]de Carvalho, Cicilia [UNESP]de Marino, IvanPereira, Paulo S.Soares, Andreimar M.Dal-Pai-Silva, Maeli [UNESP]Usón, IsabelFontes, Marcos R.M. [UNESP]2023-07-29T12:34:41Z2023-07-29T12:34:41Z2023-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article105-115http://dx.doi.org/10.1016/j.biochi.2022.10.011Biochimie, v. 206, p. 105-115.6183-16380300-9084http://hdl.handle.net/11449/24620910.1016/j.biochi.2022.10.0112-s2.0-85140977960Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBiochimieinfo:eu-repo/semantics/openAccess2023-07-29T12:34:41Zoai:repositorio.unesp.br:11449/246209Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T15:16:32.566846Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
title Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
spellingShingle Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
Borges, Rafael J. [UNESP]
MMV
Myotoxic inhibitor
PLA2-Like proteins
Snake venom
Tabernaemontana catharinensis
title_short Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
title_full Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
title_fullStr Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
title_full_unstemmed Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
title_sort Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
author Borges, Rafael J. [UNESP]
author_facet Borges, Rafael J. [UNESP]
Cardoso, Fábio F. [UNESP]
de Carvalho, Cicilia [UNESP]
de Marino, Ivan
Pereira, Paulo S.
Soares, Andreimar M.
Dal-Pai-Silva, Maeli [UNESP]
Usón, Isabel
Fontes, Marcos R.M. [UNESP]
author_role author
author2 Cardoso, Fábio F. [UNESP]
de Carvalho, Cicilia [UNESP]
de Marino, Ivan
Pereira, Paulo S.
Soares, Andreimar M.
Dal-Pai-Silva, Maeli [UNESP]
Usón, Isabel
Fontes, Marcos R.M. [UNESP]
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Institute of Molecular Biology of Barcelona (IBMB-CSIC)
Instituto Federal de Goiás (IF-GO)
Unidade Rondônia
Passeig Lluís Companys
dc.contributor.author.fl_str_mv Borges, Rafael J. [UNESP]
Cardoso, Fábio F. [UNESP]
de Carvalho, Cicilia [UNESP]
de Marino, Ivan
Pereira, Paulo S.
Soares, Andreimar M.
Dal-Pai-Silva, Maeli [UNESP]
Usón, Isabel
Fontes, Marcos R.M. [UNESP]
dc.subject.por.fl_str_mv MMV
Myotoxic inhibitor
PLA2-Like proteins
Snake venom
Tabernaemontana catharinensis
topic MMV
Myotoxic inhibitor
PLA2-Like proteins
Snake venom
Tabernaemontana catharinensis
description Snake envenomation is an ongoing global health problem and tropical neglected disease that afflicts millions of people each year. The only specific treatment, antivenom, has several limitations that affects its proper distribution to the victims and its efficacy against local effects, such as myonecrosis. The main responsible for this consequence are the phospholipases A2 (PLA2) and PLA2-like proteins, such as BthTX-I from Bothrops jararacussu. Folk medicine resorts to plants such as Tabernaemontana catharinensis to palliate these and other snakebite effects. Here, we evaluated the effect of its root bark extract and one of its isolated compounds, 12-methoxy-4-methyl-voachalotine (MMV), against the in vitro paralysis and muscle damage induced by BthTX-I. Secondary and quaternary structures of BthTX-I were not modified by the interaction with MMV. Instead, this compound interacted in an unprecedented way with the region inside the toxin hydrophobic channel and promoted a structural change in Val31, loop 58–71 and Membrane Disruption Site. Thus, we hypothesize that MMV inhibits PLA2-like proteins by preventing entrance of fatty acid into the hydrophobic channel. These data may explain the traditional use of T. catharinensis extract and confirm MMV as a promising candidate to complement antivenom or a structural guide to develop more effective inhibitors.
publishDate 2023
dc.date.none.fl_str_mv 2023-07-29T12:34:41Z
2023-07-29T12:34:41Z
2023-03-01
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/10.1016/j.biochi.2022.10.011
Biochimie, v. 206, p. 105-115.
6183-1638
0300-9084
http://hdl.handle.net/11449/246209
10.1016/j.biochi.2022.10.011
2-s2.0-85140977960
url http://dx.doi.org/10.1016/j.biochi.2022.10.011
http://hdl.handle.net/11449/246209
identifier_str_mv Biochimie, v. 206, p. 105-115.
6183-1638
0300-9084
10.1016/j.biochi.2022.10.011
2-s2.0-85140977960
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biochimie
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 105-115
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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