New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , |
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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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 |
|
_version_ |
1808129440995082240 |