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

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dc.contributor.authorMoraes, Jeane do Nascimento
dc.contributor.authorFrancisco, Aleff Ferreira [UNESP]
dc.contributor.authorDill, Leandro Moreira
dc.contributor.authorDiniz, Rafaela Souza
dc.contributor.authorde Oliveira, Claudia Siqueira
dc.contributor.authorda Silva, Tainara Maiane Rodrigues
dc.contributor.authorCaldeira, Cleópatra Alves da Silva
dc.contributor.authorCorrêa, Edailson de Alcântara
dc.contributor.authorCoutinho-Neto, Antônio
dc.contributor.authorZanchi, Fernando Berton
dc.contributor.authorFontes, Marcos Roberto de Mattos [UNESP]
dc.contributor.authorSoares, Andreimar Martins
dc.contributor.authorCalderon, Leonardo de Azevedo
dc.contributor.institutionOswaldo Cruz Foundation (FIOCRUZ)
dc.contributor.institutionFederal University of Rondônia (UNIR)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionINCT-EPIAMO
dc.contributor.institutionSmart Active Ingredients Lab (SAIL)
dc.contributor.institutionUniversity of Buenos Aires (UBA)
dc.contributor.institutionScience and Technology of Rondonia (IFRO)
dc.contributor.institutionSão Lucas University Center (UniSL)
dc.contributor.institutionAparicio Carvalho University Center (FIMCA)
dc.date.accessioned2023-07-29T13:32:34Z
dc.date.available2023-07-29T13:32:34Z
dc.date.issued2022-01-01
dc.description.abstractBackground: 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.en
dc.description.affiliationCenter for the Study of Biomolecules Applied to Health (CEBio) Oswaldo Cruz Foundation (FIOCRUZ), RO
dc.description.affiliationGraduate Program in Experimental Biology (PGBIOEXP) Department of Medicine (DEPMED) Federal University of Rondônia (UNIR), RO
dc.description.affiliationDepartment of Biophysics and Pharmacology Botucatu Biosciences Institute (IBB) São Paulo State University (UNESP), SP
dc.description.affiliationLaboratory of Biotechnology of Proteins and Bioactive Compounds (LABIOPROT) Oswaldo Cruz Foundation (FIOCRUZ), RO
dc.description.affiliationNational Institute of Science and Technology of Epidemiology of the Western Amazon INCT-EPIAMO, RO
dc.description.affiliationSmart Active Ingredients Lab (SAIL), RO
dc.description.affiliationFaculty of Medicine University of Buenos Aires (UBA)
dc.description.affiliationFederal Institute of Education Science and Technology of Rondonia (IFRO), RO
dc.description.affiliationBioinformatics and Medicinal Chemistry Laboratory (LABIOQUIM) Oswaldo Cruz Foundation (FIOCRUZ), RO
dc.description.affiliationSão Lucas University Center (UniSL), RO
dc.description.affiliationAparicio Carvalho University Center (FIMCA), RO
dc.description.affiliationUnespDepartment of Biophysics and Pharmacology Botucatu Biosciences Institute (IBB) São Paulo State University (UNESP), SP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.identifierhttp://dx.doi.org/10.1590/1678-9199-JVATITD-2022-0002
dc.identifier.citationJournal of Venomous Animals and Toxins Including Tropical Diseases, v. 28.
dc.identifier.doi10.1590/1678-9199-JVATITD-2022-0002
dc.identifier.issn1678-9199
dc.identifier.issn1678-9180
dc.identifier.scopus2-s2.0-85143912454
dc.identifier.urihttp://hdl.handle.net/11449/248030
dc.language.isoeng
dc.relation.ispartofJournal of Venomous Animals and Toxins Including Tropical Diseases
dc.sourceScopus
dc.subjectCathepsin D
dc.subjectEnzyme complex
dc.subjectPhospholipases A2
dc.subjectSnake venom
dc.titleNew multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2en
dc.typeArtigo

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