Crystallographic Structure and Antiglioma Potential of <i>Centrolobium microchaete</i> Seed Lectin

The genus <i>Centrolobium</i> comprises species of Neotropical trees with seeds that possess medicinal and bioactive applications. Lectins from this genus exhibit anti-inflammatory and immunomodulatory effects, influencing the activation of the immune system. This study focuses on characterizing the structure and carbohydrate-binding properties of the lectin from <i>Centrolobium microchaete</i> (CML) and evaluating its potential against gliomas. The structure of the lectin in complex with methyl-mannose-α1,3-mannose (MDM) was resolved using X-ray crystallography at 1.3 Å resolution, with its interactions further analyzed through molecular dynamics simulations. Structurally, CML adopts a β-sandwich motif and assembles into canonical dimers. <i>In vitro</i> assays revealed that CML reduced the viability of C6 glioma cells, although only at high concentrations, without impacting cell migration or morphology. CML activated autophagic processes, albeit with lower efficacy compared with other mannose-specific lectins. The limited antiglioma activity of CML may be linked to its inability to form tetramers and unusual specificity toward asymmetric glycans, both crucial features for interactions with cellular glycans and the activation of signaling pathways. This study represents the first investigation of the antiglioma potential of a mannose-specific lectin from the Dalbergieae tribe, highlighting both its structural characteristics and functional limitations.