Análise estrutural de uma lectina de Bauhinia ungulata por ferramentas de bioinformática

Abstract

Carbohydrates are multifunctional molecules involved in the storage information. The role of coding biological information is mainly played by the carbohydrates present in the plasma membrane, which constitute the glycocalyx of a cell. These surface glycans are involved in many functions, like cell recognition, cell adhesion, blood clothing, immune response, cell migration, parasite-host interaction, metastasis etc. Changes in the pattern of cell surface glycosylation may indicate abnormalities, as happens in many cancers. Among these changes, one that deserves attention is the overexpression of the Tn antigen, whose early detection in these diseases is extremely importante for its diagnosis. Such detection can be performed using lectins. Lectins are proteins or glycoproteins that recognize carbohydrates in a specific manner without altering their structure. Plant lectins, mainly from leguminous plants (Fabaceae family) are the most studied ones. Within the legumes, lectins belonging to the Caesalpinioideae subfamily still have few data regarding their structure-function relationship. In this subfamily, one of the best known genera is Bauhinia, whose representatives are popularly called "cow's hoof". Several Bauhinia lectins have already been purified and have various biological activities, such as anti-inflammatory, anticoagulant, immunomodulatory, anti-tumor and cancer cell markers. In order to assess these latter activities more thoroughly and to evaluate the potential of Bauhinia lectins as tools in oncology studies, Bauhinia ungulata seed lectin (BUL) was chosen as the object of study to conduct a structural analysis through bioinformatics tools. This work aimed to determine the three-dimensional structure of BUL by homology modeling and to evaluate its interaction with different ligands through molecular docking. The results obtained from the modeling were satisfactory, according to the validation parameters. It was observed that the BUL monomer is composed of a β-sandwich fold or jellyroll motif, which is a characteristic of legume lectins. The docking results showed that BUL interacts favorably with N-acetyl-D-galactosamine (GalNAc), α-lactose, Tn antigen, Tn antigen-derived peptides and two forms of a trisaccharide, one containing fucose and one containing GalNAc on its terminal portion. From these results, it can be inferred that this lectin may be a potential marker in cell lines which overexpress Tn antigen and fucose on its surface. However, more advanced structural studies, such as molecular dynamics simulations, as well as in vitro and in vivo tests, are needed to confirm these potential applications of BUL.