Structural and functional studies of a snake venom phospholipase A2-like protein complexed to an inhibitor from Tabernaemontana catharinensis
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , |
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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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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1808128492698599424 |