Structural analysis of ConBr reveals molecular correlation between the carbohydrate recognition domain and endothelial NO synthase activation

• Published in: Biochemical and biophysical research communications Vol. 408; no. 4; pp. 566 - 570
• Main Authors: Bezerra, Eduardo Henrique Salviano, Rocha, Bruno Anderson Matias, Nagano, Celso Shiniti, Bezerra, Gustavo de Arruda, Moura, Tales Rocha de, Bezerra, Maria Júlia Barbosa, Benevides, Raquel Guimarães, Sampaio, Alexandre Holanda, Assreuy, Ana Maria Sampaio, Delatorre, Plínio, Cavada, Benildo Sousa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.05.2011
• Subjects: Canavalia - metabolism; Canavalia brasiliensis; Carbohydrate recognition domain; Carbohydrates; Crystallography, X-Ray; Endothelial NO synthase; Enzyme Activation; Lectin; Nitric Oxide Synthase Type III - chemistry; Plant Lectins - chemistry; Protein Conformation; Smooth muscle; Lectin; Smooth muscle; Canavalia brasiliensis; Endothelial NO synthase; Carbohydrate recognition domain
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.04.061

► Canavalia brasiliensis seed lectin crystal structure and the prediction of dimannoside biding by docking were used to structure/function analysis. ► The relation between the carbohydrate binding domain and the induction to product NO can be demonstrated by CRD design. ► ConBr presents similar distances to ConM, but the reduction of biological activity is explained by the smaller CRD volume. Diocleinae lectins are highly homologous in their primary structure which features metal binding sites and a carbohydrate recognition domain (CRD). Differences in the biological activity of legume lectins have been widely investigated using hemagglutination inhibition assays, isothermal titration microcalorimetry and co-crystallization with mono- and oligosaccharides. Here we report a new lectin crystal structure (ConBr) extracted from seeds of Canavalia brasiliensis, predict dimannoside binding by docking, identify the α-aminobutyric acid (Abu) binding pocket and compare the CRD of ConBr to that of homologous lectins. Based on the hypothesis that the carbohydrate affinity of lectins depends on CRD configuration, the relationship between tridimensional structure and endothelial NO synthase activation was used to clarify differences in biological activity. Our study established a correlation between the position of CRD amino acid side chains and the stimulation of NO release from endothelium.