Structural basis for both pro- and anti-inflammatory response induced by mannose-specific legume lectin from Cymbosema roseum

• Autor(a) principal: Rocha, Bruno Anderson Matias da
• Data de Publicação: 2011
• Outros Autores: Delatorre, Plínio, Oliveira, Taianá Maia, Benevides, R. G., Pires, Alana de Freitas, Sousa, Albertina A.S., Souza, Luis A.G., Assreuy, Ana Maria Sampaio, Debray, Henri, Azevedo, Walter Filgueira de, Sampaio, Alexandre Holanda, Cavada, B. S.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional do INPA
• Texto Completo: https://repositorio.inpa.gov.br/handle/1/16225
• topic: 2 Aminobutyric Acid; Antiinflammatory Agent; Calcium; Carbohydrate; Carrageenan; Cymbosema Roseum Lectin 1; Lectin; Manganese; Unclassified Drug; Animals Experiment; Animals Model; Antiinflammatory Activity; Binding Affinity; Binding Site; Controlled Study; Crystal Structure; Cymbosema Roseum; Drug Effect; Drug Screening; Drug Structure; Edema; Lectin Binding; Legume; Male; Molecular Docking; Nonhuman; Rat; Sequence Analysis; Tandem Mass Spectrometry; X Ray Crystallography; Cymbosema Roseum

Legume lectins, despite high sequence homology, express diverse biological activities that vary in potency and efficacy. In studies reported here, the mannose-specific lectin from Cymbosema roseum (CRLI), which binds N-glycoproteins, shows both pro-inflammatory effects when administered by local injection and anti-inflammatory effects when by systemic injection. Protein sequencing was obtained by Tandem Mass Spectrometry and the crystal structure was solved by X-ray crystallography using a Synchrotron radiation source. Molecular replacement and refinement were performed using CCP4 and the carbohydrate binding properties were described by affinity assays and computational docking. Biological assays were performed in order to evaluate the lectin edematogenic activity. The crystal structure of CRLI was established to a 1.8 Å resolution in order to determine a structural basis for these differing activities. The structure of CRLI is closely homologous to those of other legume lectins at the monomer level and assembles into tetramers as do many of its homologues. The CRLI carbohydrate binding site was predicted by docking with a specific inhibitory trisaccharide. CRLI possesses a hydrophobic pocket for the binding of α-aminobutyric acid and that pocket is occupied in this structure as are the binding sites for calcium and manganese cations characteristic of legume lectins. CRLI route-dependent effects for acute inflammation are related to its carbohydrate binding domain (due to inhibition caused by the presence of α-methyl-mannoside), and are based on comparative analysis with ConA crystal structure. This may be due to carbohydrate binding site design, which differs at Tyr12 and Glu205 position. © 2011 Elsevier Masson SAS. All rights reserved.