Computational Characterization of Banana Lectins from Musa acuminata and M. balbisiana Reveals BanLec-Glycan Interactions Relevant to Hypermannosylation in Breast Cancer

Banana Lectin (BanLec) is a mannose-binding jacalin-related lectin that has attracted considerable scientific interest due to its affinity toward high-mannose-type N-glycans and its immunomodulatory and antiviral properties. It also has the potential to suppress cancer cell proliferation and stimulate macrophage activity. In this study, evolutionary relationships among BanLec sequences across the Musa genus were also examined, while the primary focus was the identification and characterization of BanLec-encoding genes from Musa acuminata subsp. malaccensis (Malaysian Dwarf Banana) and Musa balbisiana (Banana Klutuk Wulung), with emphasis on their molecular properties and potential interactions with a hypermannosylated N-glycan structure (Man8GlcNAc2) reported to be abundant in breast cancer. Seven and four high-confidence BanLec protein sequences were identified from M. acuminata subsp. malaccensis and M. balbisiana genomes, respectively, which all share conserved structural domains characteristic of BanLec with variable exon-intron organizations. Gene locations, duplications, and synteny analyses revealed lineage-specific diversification of lectin genes within each species and between the two Musa genomes. The identified BanLec proteins were modelled and then evaluated by molecular docking and molecular dynamics simulations using a hypermannosylated N-glycan structure. The computational binding analyses demonstrate that BanLec variants from different Musa genomes exhibit distinct energetic and structural preferences toward the hypermannosylated N-glycan structure. Among the tested complexes, Ma09_t10450 (M. acuminata subsp. malaccensis) showed the most stable interaction, followed by Mba09_g09930 (M. balbisiana), each demonstrating strongly favourable binding free energies (ΔG ≤ -22.43 ± 3.01 kcal mol⁻¹ and ΔG ≤ -17.87 ± 10.81 kcal mol⁻¹ respectively) and therefore considered suitable candidates for lectin binding assays conducted at neutral pH, 300 K, and physiological ionic strength. These findings strengthen BanLec's potential as a promising candidate for lectin-based biomarker development and glycan-targeted therapeutic applications.