Crystal structure of DlyL, a mannose-specific lectin from Dioclea lasiophylla Mart. Ex Benth seeds that display cytotoxic effects against C6 glioma cells

• Published in: International journal of biological macromolecules Vol. 114; pp. 64 - 76
• Main Authors: Leal, Rodrigo Bainy, Pinto-Junior, Vanir Reis, Osterne, Vinicius Jose Silva, Wolin, Ingrid Alessandra Victoria, Nascimento, Ana Paula Machado, Neco, Antonio Hadson Bastos, Araripe, David Alencar, Welter, Priscilla Gomes, Neto, Corneville Correia, Correia, Jorge Luis Almeida, Rocha, Cintia Renata Costa, Nascimento, Kyria Santiago, Cavada, Benildo Sousa
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.07.2018
• Subjects: Animals; Apoptosis - drug effects; Binding Sites; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Crystal structure; Crystallization; Dioclea - chemistry; DlyL; Glioma; Mannose-Binding Lectins - chemistry; Mannose-Binding Lectins - isolation & purification; Mannose-Binding Lectins - pharmacology; Molecular Docking Simulation; Plant Lectins - chemistry; Plant Lectins - isolation & purification; Plant Lectins - pharmacology; Protein Binding; Protein Conformation; Rats; Seeds - chemistry; Glioma; DlyL; Crystal structure
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2018.03.080

Lectins are a class of carbohydrate-binding proteins or glycoproteins with diverse specificities and functions. The determination and characterization of the three-dimensional structures of these proteins are keys to understanding their biological effects. Recent studies have explored the anticancer potential of Diocleinae lectins (from Leguminoseae family), evaluating their antiproliferative effect and their ability to induce glioma cell death via apoptosis and autophagy. In this work, the three-dimensional structure of Dioclea lasiophylla seed lectin (DlyL) complexed with Xman (5-bromo-6-chloro-3-indolyl-α-d-mannopyranoside) was determined by X-ray crystallography. Moreover, interactions with relevant N-glycans were evaluated by molecular docking. DlyL presented the jellyroll motif, and both metal binding site (MBS) and carbohydrate-recognition domain (CRD) were determined and characterized. Molecular docking simulations indicated that DlyL interacts favorably with N-glycans, especially those of the complex and hybrid types, unlike previously studied Diocleinae lectins. DlyL also showed antitumor potential against rat C6 glioma cells impairing cell migration, inducing autophagy and cell death via activation of caspase 3. These results indicate that small structural differences among Diocleinae lectins can, in turn, result in differential modulation of autophagy and cell apoptosis processes. •We present the crystal structure Dioclea lasiophylla Mart. Ex Benth seed lectin (DlyL).•Molecular docking of DlyL with N-glycans was performed.•The antiglioma effect of DlyL was determined in vitro.