Análise estrutural da lectina de Dioclea lasiocarpa: uma proteína indutora de apoptose em células de glioma da linhagem C6

Abstract

Lectins are multidomain proteins with the ability to recognize carbohydrates in a specific way, in addition to interacting with molecules from other classes, such as hydrophobic compounds or secondary metabolites. Structural characterization of these molecules is crucial to understanding their function and activity in organisms and systems. An area with high potential of application for lectins is cancerology since most cancer cells exhibit alterations in glycosylation patterns and lectins may be able to recognize these alterations. In this work, the lectin isolated from the seed of Dioclea lasiocarpa, DLL, had its crystallographic structure determined and characterized, and it was also evaluated for the possibility of interaction with different carbohydrates by molecular docking. Lectin antiglioma potential was evaluated against C6 lineage glioma cells. The results obtained evidenced a high degree of similarity of DLL with other lectins isolated from legumes of the same subtribe, presenting a jellyroll-type binding motif (β-sandwich) and a metal binding site stabilizing the carbohydrate recognition domain. DLL demonstrated differential interactions with carbohydrates, varying according to the type of glycosidic bond present in the ligands. The elucidated molecule presented, as biological activity, a reduction in cell viability in cancer cells of the C6 lineage and showed strong antiglioma activity by mechanisms involving the activation of caspases 3. It was possible to conclude that the target molecule of this work recognizes carbohydrates present in cells of glioma and presents itself as a promising candidate to proceed in diagnostic tests and alternative therapy to mitigate resistance to glioma, a tumor well known to be resistant to cell death induction.