Mechanistic insight into the inhibition of α-glucosidase by millet Prolamin K3ZAN2: An integrated experimental and molecular simulation study.

ABSTRACT: Dietary proteins with α-glucosidase inhibitory activity are gaining interest for their role in supporting glycemic control. Here, we report that millet-derived prolamin K3ZAN2 modulates α-glucosidase activity through a flexible-region-mediated mechanism. K3ZAN2 exhibited an IC₅₀ of 4.15 mg/mL, with its proteinaceous nature confirmed by UV spectroscopy and SDS-PAGE. Molecular docking showed that flexible residues Thr11, Ser18, Gln20, Gly26, and Gln64 interact with α-glucosidase active site residues via hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations (102 ns) indicated structural stability (RMSD ∼0.2 nm), compactness (Rg ∼1.9 nm), and persistent hydrogen bonding. Binding free energy (ΔG = -15,536.71 kJ/mol) supported strong affinity. Principal component and free e

SUBMITTER: Zhao L 

PROVIDER: S-EPMC12275070 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature