New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2

Detalhes bibliográficos
Autor(a) principal: Moraes, Jeane do Nascimento
Data de Publicação: 2022
Outros Autores: Francisco, Aleff Ferreira [UNESP], Dill, Leandro Moreira, Diniz, Rafaela Souza, de Oliveira, Claudia Siqueira, da Silva, Tainara Maiane Rodrigues, Caldeira, Cleópatra Alves da Silva, Corrêa, Edailson de Alcântara, Coutinho-Neto, Antônio, Zanchi, Fernando Berton, Fontes, Marcos Roberto de Mattos [UNESP], Soares, Andreimar Martins, Calderon, Leonardo de Azevedo
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1590/1678-9199-JVATITD-2022-0002
http://hdl.handle.net/11449/248030
Resumo: Background: Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme. Methods: An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A2 (svPLA2), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA2. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA2 was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques. Conclusion: The present study suggests the versatility of human CatD and svPLA2, showing that these enzymes can form a fully functional new enzymatic complex.
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spelling New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2Cathepsin DEnzyme complexPhospholipases A2Snake venomBackground: Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme. Methods: An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A2 (svPLA2), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA2. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA2 was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques. Conclusion: The present study suggests the versatility of human CatD and svPLA2, showing that these enzymes can form a fully functional new enzymatic complex.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Center for the Study of Biomolecules Applied to Health (CEBio) Oswaldo Cruz Foundation (FIOCRUZ), ROGraduate Program in Experimental Biology (PGBIOEXP) Department of Medicine (DEPMED) Federal University of Rondônia (UNIR), RODepartment of Biophysics and Pharmacology Botucatu Biosciences Institute (IBB) São Paulo State University (UNESP), SPLaboratory of Biotechnology of Proteins and Bioactive Compounds (LABIOPROT) Oswaldo Cruz Foundation (FIOCRUZ), RONational Institute of Science and Technology of Epidemiology of the Western Amazon INCT-EPIAMO, ROSmart Active Ingredients Lab (SAIL), ROFaculty of Medicine University of Buenos Aires (UBA)Federal Institute of Education Science and Technology of Rondonia (IFRO), ROBioinformatics and Medicinal Chemistry Laboratory (LABIOQUIM) Oswaldo Cruz Foundation (FIOCRUZ), ROSão Lucas University Center (UniSL), ROAparicio Carvalho University Center (FIMCA), RODepartment of Biophysics and Pharmacology Botucatu Biosciences Institute (IBB) São Paulo State University (UNESP), SPOswaldo Cruz Foundation (FIOCRUZ)Federal University of Rondônia (UNIR)Universidade Estadual Paulista (UNESP)INCT-EPIAMOSmart Active Ingredients Lab (SAIL)University of Buenos Aires (UBA)Science and Technology of Rondonia (IFRO)São Lucas University Center (UniSL)Aparicio Carvalho University Center (FIMCA)Moraes, Jeane do NascimentoFrancisco, Aleff Ferreira [UNESP]Dill, Leandro MoreiraDiniz, Rafaela Souzade Oliveira, Claudia Siqueirada Silva, Tainara Maiane RodriguesCaldeira, Cleópatra Alves da SilvaCorrêa, Edailson de AlcântaraCoutinho-Neto, AntônioZanchi, Fernando BertonFontes, Marcos Roberto de Mattos [UNESP]Soares, Andreimar MartinsCalderon, Leonardo de Azevedo2023-07-29T13:32:34Z2023-07-29T13:32:34Z2022-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1590/1678-9199-JVATITD-2022-0002Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 28.1678-91991678-9180http://hdl.handle.net/11449/24803010.1590/1678-9199-JVATITD-2022-00022-s2.0-85143912454Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Venomous Animals and Toxins Including Tropical Diseasesinfo:eu-repo/semantics/openAccess2023-07-29T13:32:34Zoai:repositorio.unesp.br:11449/248030Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:35:24.776663Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
title New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
spellingShingle New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
Moraes, Jeane do Nascimento
Cathepsin D
Enzyme complex
Phospholipases A2
Snake venom
title_short New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
title_full New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
title_fullStr New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
title_full_unstemmed New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
title_sort New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
author Moraes, Jeane do Nascimento
author_facet Moraes, Jeane do Nascimento
Francisco, Aleff Ferreira [UNESP]
Dill, Leandro Moreira
Diniz, Rafaela Souza
de Oliveira, Claudia Siqueira
da Silva, Tainara Maiane Rodrigues
Caldeira, Cleópatra Alves da Silva
Corrêa, Edailson de Alcântara
Coutinho-Neto, Antônio
Zanchi, Fernando Berton
Fontes, Marcos Roberto de Mattos [UNESP]
Soares, Andreimar Martins
Calderon, Leonardo de Azevedo
author_role author
author2 Francisco, Aleff Ferreira [UNESP]
Dill, Leandro Moreira
Diniz, Rafaela Souza
de Oliveira, Claudia Siqueira
da Silva, Tainara Maiane Rodrigues
Caldeira, Cleópatra Alves da Silva
Corrêa, Edailson de Alcântara
Coutinho-Neto, Antônio
Zanchi, Fernando Berton
Fontes, Marcos Roberto de Mattos [UNESP]
Soares, Andreimar Martins
Calderon, Leonardo de Azevedo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Oswaldo Cruz Foundation (FIOCRUZ)
Federal University of Rondônia (UNIR)
Universidade Estadual Paulista (UNESP)
INCT-EPIAMO
Smart Active Ingredients Lab (SAIL)
University of Buenos Aires (UBA)
Science and Technology of Rondonia (IFRO)
São Lucas University Center (UniSL)
Aparicio Carvalho University Center (FIMCA)
dc.contributor.author.fl_str_mv Moraes, Jeane do Nascimento
Francisco, Aleff Ferreira [UNESP]
Dill, Leandro Moreira
Diniz, Rafaela Souza
de Oliveira, Claudia Siqueira
da Silva, Tainara Maiane Rodrigues
Caldeira, Cleópatra Alves da Silva
Corrêa, Edailson de Alcântara
Coutinho-Neto, Antônio
Zanchi, Fernando Berton
Fontes, Marcos Roberto de Mattos [UNESP]
Soares, Andreimar Martins
Calderon, Leonardo de Azevedo
dc.subject.por.fl_str_mv Cathepsin D
Enzyme complex
Phospholipases A2
Snake venom
topic Cathepsin D
Enzyme complex
Phospholipases A2
Snake venom
description Background: Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme. Methods: An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A2 (svPLA2), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA2. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA2 was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques. Conclusion: The present study suggests the versatility of human CatD and svPLA2, showing that these enzymes can form a fully functional new enzymatic complex.
publishDate 2022
dc.date.none.fl_str_mv 2022-01-01
2023-07-29T13:32:34Z
2023-07-29T13:32:34Z
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/10.1590/1678-9199-JVATITD-2022-0002
Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 28.
1678-9199
1678-9180
http://hdl.handle.net/11449/248030
10.1590/1678-9199-JVATITD-2022-0002
2-s2.0-85143912454
url http://dx.doi.org/10.1590/1678-9199-JVATITD-2022-0002
http://hdl.handle.net/11449/248030
identifier_str_mv Journal of Venomous Animals and Toxins Including Tropical Diseases, v. 28.
1678-9199
1678-9180
10.1590/1678-9199-JVATITD-2022-0002
2-s2.0-85143912454
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Venomous Animals and Toxins Including Tropical Diseases
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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