8UX7

Dioclea megacarpa lectin (DmegA) complexed with X-Man

Summary for 8UX7

• Entry DOI: 10.2210/pdb8ux7/pdb
• Descriptor: Dioclea megacarpa lectin, MANGANESE (II) ION, CALCIUM ION, ... (7 entities in total)
• Functional Keywords: lectin, legume, cona-like, dioclea, sugar binding protein
• Biological source: Macropsychanthus megacarpus
• Total number of polymer chains: 2
• Total formula weight: 52263.02

Authors

Oliveira, M.V.,De Sloover, G.,Osterne, V.J.S.,Pinto-Junior, V.R.,Sacramento-Neto, J.C.,Van Damme, E.J.M.,Nascimento, K.S.,Cavada, B.S. (deposition date: 2023-11-09, release date: 2023-11-29, Last modification date: 2026-04-15)

Primary citation

Osterne, V.J.S.,Ervijn, L.,Oliveira, M.V.,Pinto-Junior, V.R.,Serna, S.,Reichardt, N.C.,Nascimento, K.S.,Van Damme, E.J.M.,Cavada, B.S.
Crystal structure, glycan specificity, and induction of cellular stress by the legume lectin DmegA.
Int.J.Biol.Macromol., 358:151795-151795, 2026

PubMed Abstract: The precise molecular mechanisms translating glycan recognition by plant lectins into cancer cell death remain incompletely understood. To address this gap, this study examines the cytotoxic response elicited by the mannose-specific legume lectin DmegA by integrating structural biology, glycan profiling, and cellular assays to map events from cell surface binding to apoptosis. The 2.4 Å crystal structure reveals a canonical ConA-like fold with conserved carbohydrate-recognition and Ca/Mn coordination sites. Glycan microarray and molecular docking analyses indicate preferential recognition of mannose-rich N-glycan motifs, including the core trimannoside of N-glycans, consistent with the interaction of the lectin with a broad range of glycoproteins. Glycan-dependent internalization of DmegA in PANC-1 cells was associated with increased EDEM transcript levels, whereas no statistically significant change in CHOP transcript levels was detected, alongside elevated ROS levels and caspase activation. The pro-apoptotic gene PUMA was upregulated, suggesting a potential connection between cellular stress responses and mitochondrial apoptosis. While the observation of EDEM induction in the absence of statistically significant CHOP upregulation represents a low-power preliminary finding, the combined data support a cellular phenotype characterized by oxidative stress, caspase activation, and ER-associated transcriptional changes. Given its broad glycan recognition and lack of tumor selectivity, DmegA is not directly suitable for therapeutic applications, but the structural and mechanistic insights provided here inform future engineering or targeting strategies aimed at improving lectin selectivity.

PubMed: 41932485
DOI: 10.1016/j.ijbiomac.2026.151795

Experimental method

X-RAY DIFFRACTION (2.2 Å)