Structural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanism

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dc.contributor.authorSalvador, Guilherme H. M. [UNESP]
dc.contributor.authorDreyer, Thiago R. [UNESP]
dc.contributor.authorGomes, Antoniel A. S. [UNESP]
dc.contributor.authorCavalcante, Walter L. G. [UNESP]
dc.contributor.authorDos Santos, Juliana I. [UNESP]
dc.contributor.authorGandin, César A. [UNESP]
dc.contributor.authorDe Oliveira Neto, Mário [UNESP]
dc.contributor.authorGallacci, Márcia [UNESP]
dc.contributor.authorFontes, Marcos R. M. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.date.accessioned2018-12-11T17:37:43Z
dc.date.available2018-12-11T17:37:43Z
dc.date.issued2018-12-01
dc.description.abstractLocal myonecrosis is the main event resulting from snakebite envenomation by the Bothrops genus and, frequently, it is not efficiently neutralized by antivenom administration. Proteases, phospholipases A2 (PLA2) and PLA2-like toxins are found in venom related to muscle damage. Functional sites responsible for PLA2-like toxins activity have been proposed recently; they consist of a membrane docking-site and a membrane rupture-site. Herein, a combination of functional, biophysical and crystallographic techniques was used to characterize the interaction between suramin and MjTX-I (a PLA2-like toxin from Bothrops moojeni venom). Functional in vitro neuromuscular assays were performed to study the biological effects of the protein-ligand interaction, demonstrating that suramin neutralizes the myotoxic effect of MjTX-I. Calorimetric assays showed two different binding events: (i) inhibitor-protein interactions and (ii) toxin oligomerization processes. These hypotheses were also corroborated with dynamic light and small angle X-ray scattering assays. The crystal structure of the MjTX-I/suramin showed a totally different interaction mode compared to other PLA2-like/suramin complexes. Thus, we suggested a novel myotoxic mechanism for MjTX-I that may be inhibited by suramin. These results can further contribute to the search for inhibitors that will efficiently counteract local myonecrosis in order to be used as an adjuvant of conventional serum therapy.en
dc.description.affiliationUniversidade Estadual Paulista (UNESP) Instituto de Biociências Dep. de Física e Biofísica
dc.description.affiliationUniversidade Federal de Minas Gerais (UFMG) Instituto de Ciências Biológicas Dep. de Farmacologia
dc.description.affiliationUniversidade Estadual Paulista (UNESP) Instituto de Biociências Dep. de Farmacologia
dc.description.affiliationUnespUniversidade Estadual Paulista (UNESP) Instituto de Biociências Dep. de Física e Biofísica
dc.description.affiliationUnespUniversidade Estadual Paulista (UNESP) Instituto de Biociências Dep. de Farmacologia
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.identifierhttp://dx.doi.org/10.1038/s41598-018-28584-7
dc.identifier.citationScientific Reports, v. 8, n. 1, 2018.
dc.identifier.doi10.1038/s41598-018-28584-7
dc.identifier.file2-s2.0-85049855558.pdf
dc.identifier.issn2045-2322
dc.identifier.lattes9353490382598257
dc.identifier.scopus2-s2.0-85049855558
dc.identifier.urihttp://hdl.handle.net/11449/180026
dc.language.isoeng
dc.relation.ispartofScientific Reports
dc.relation.ispartofsjr1,533
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.titleStructural and functional characterization of suramin-bound MjTX-I from Bothrops moojeni suggests a particular myotoxic mechanismen
dc.typeArtigo
unesp.author.lattes9353490382598257
unesp.author.orcid0000-0002-4634-6221[9]

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Artigos - Farmacologia - IBB