The allosteric activation mechanism of a phospholipase A2-like toxin from Bothrops jararacussu venom: a dynamic description

Página do item simplificado
dc.contributor.authorGomes, Antoniel A. S. [UNESP]
dc.contributor.authorCardoso, Fabio F. [UNESP]
dc.contributor.authorSouza, Maximilia F.
dc.contributor.authorOliveira, Cristiano L. P.
dc.contributor.authorPerahia, David
dc.contributor.authorMagro, Angelo J. [UNESP]
dc.contributor.authorFontes, Marcos R. M. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionCNRS
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2021-06-25T10:12:08Z
dc.date.available2021-06-25T10:12:08Z
dc.date.issued2020-12-01
dc.description.abstractThe activation process of phospholipase A2-like (PLA2-like) toxins is a key step in their molecular mechanism, which involves oligomeric changes leading to the exposure of specific sites. Few studies have focused on the characterization of allosteric activators and the features that distinguish them from inhibitors. Herein, a comprehensive study with the BthTX-I toxin from Bothrops jararacussu venom bound or unbound to α-tocopherol (αT) was carried out. The oligomerization state of BthTX-I bound or unbound to αT in solution was studied and indicated that the toxin is predominantly monomeric but tends to oligomerize when complexed with αT. In silico molecular simulations showed the toxin presents higher conformational changes in the absence of αT,which suggests that it is important to stabilize the structure of the toxin. The transition between the two states (active/inactive) was also studied, showing that only the unbound BthTX-I system could migrate to the inactive state. In contrast, the presence of αT induces the toxin to leave the inactive state, guiding it towards the active state, with more regions exposed to the solvent, particularly its active site. Finally, the structural determinants necessary for a molecule to be an inhibitor or activator were analyzed in light of the obtained results.en
dc.description.affiliationDepartamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP)
dc.description.affiliationLaboratoire de Biologie et de Pharmacologie Appliquée École Normale Supérieure Paris Saclay UMR 8113 CNRS, 4 Avenue des Sciences
dc.description.affiliationDepartamento de Física Experimental Instituto de Física Universidade de São Paulo (USP)
dc.description.affiliationDepartamento de Biotecnologia e Bioprocessos Faculdade de Ciências Agronômicas Universidade Estadual Paulista (UNESP)
dc.description.affiliationInstituto de Biotecnologia Universidade Estadual Paulista (UNESP)
dc.description.affiliationUnespDepartamento de Biofísica e Farmacologia Instituto de Biociências Universidade Estadual Paulista (UNESP)
dc.description.affiliationUnespDepartamento de Biotecnologia e Bioprocessos Faculdade de Ciências Agronômicas Universidade Estadual Paulista (UNESP)
dc.description.affiliationUnespInstituto de Biotecnologia Universidade Estadual Paulista (UNESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdCNPq: 302883/2017-7
dc.description.sponsorshipIdCNPq: 401190/2017-0
dc.description.sponsorshipIdCAPES: 88881.134154/2016-01
dc.description.sponsorshipIdCAPES: 88882.183567/2007-01
dc.identifierhttp://dx.doi.org/10.1038/s41598-020-73134-9
dc.identifier.citationScientific Reports, v. 10, n. 1, 2020.
dc.identifier.doi10.1038/s41598-020-73134-9
dc.identifier.issn2045-2322
dc.identifier.scopus2-s2.0-85091788159
dc.identifier.urihttp://hdl.handle.net/11449/205238
dc.language.isoeng
dc.relation.ispartofScientific Reports
dc.sourceScopus
dc.titleThe allosteric activation mechanism of a phospholipase A2-like toxin from Bothrops jararacussu venom: a dynamic descriptionen
dc.typeArtigo

Arquivos

Coleções

Artigos