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Structural and binding studies of a C-type galactose-binding lectin from Bothrops jararacussu snake venom.
Sartim, Marco A; Pinheiro, Matheus P; de Pádua, Ricardo A P; Sampaio, Suely V; Nonato, M Cristina.
Afiliação
  • Sartim MA; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Laboratório de Toxinologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, 14040-903, Ribeirão Preto, S.P., Brazil.
  • Pinheiro MP; Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, 14040-903, Ribeirão Preto, S.P., Brazil.
  • de Pádua RAP; Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, 14040-903, Ribeirão Preto, S.P., Brazil.
  • Sampaio SV; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Laboratório de Toxinologia, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, 14040-903, Ribeirão Preto, S.P., Brazil.
  • Nonato MC; Laboratório de Cristalografia de Proteínas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, 14040-903, Ribeirão Preto, S.P., Brazil. Electronic address: cristy@fcfrp.usp.br.
Toxicon ; 126: 59-69, 2017 Feb.
Article em En | MEDLINE | ID: mdl-28003128
BJcuL is a snake venom galactoside-binding lectin (SVgalL) isolated from Bothrops jararacussu and is involved in a wide variety of biological activities including triggering of pro-inflammatory response, disruption of microbial biofilm structure and induction of apoptosis. In the present work, we determined the crystallographic structure of BJcuL, the first holo structure of a SVgalL, and introduced the fluorescence-based thermal stability assay (Thermofluor) as a tool for screening and characterization of the binding mechanism of SVgalL ligands. BJcuL structure revealed the existence of a porous and flexible decameric arrangement composed of disulfide-linked dimers related by a five-fold symmetry. Each monomer contains the canonical carbohydrate recognition domain, a calcium ion required for BJcuL lectinic activity and a sodium ion required for protein stabilization. BJcuL thermostability was found to be induced by calcium ion and galactoside sugars which exhibit hyperbolic saturation profiles dependent on ligand concentration. Serendipitously, the gentamicin group of aminoglycoside antibiotics (gAGAs) was also identified as BJcuL ligands. On contrast, gAGAs exhibited a sigmoidal saturation profile compatible with a cooperative mechanism of binding. Thermofluor, hemagglutination inhibition assay and molecular docking strategies were used to identify a distinct binding site in BJcuL localized at the dimeric interface near the fully conserved intermolecular Cys86-Cys86 disulfide bond. The hybrid approach used in the present work provided novel insights into structural behavior and functional diversification of SVgaLs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Venenos de Crotalídeos / Proteínas de Répteis / Lectinas Tipo C Limite: Animals Idioma: En Revista: Toxicon Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Venenos de Crotalídeos / Proteínas de Répteis / Lectinas Tipo C Limite: Animals Idioma: En Revista: Toxicon Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Reino Unido