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

IF 6.5 1区农林科学 Q1 CHEMISTRY, APPLIED

Food Chemistry: X Pub Date : 2025-07-06 eCollection Date: 2025-07-01 DOI:10.1016/j.fochx.2025.102749

Liangxing Zhao, Ruikang Lin, Xinlai Dou, Qingyu Zhao, Chao Wang, Yong Xue, Qun Shen

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引用次数: 0

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 energy landscape analyses revealed conformational transitions and stable states, while dynamic cross-correlation analysis highlighted coordinated motions at the interface. These computational insights support a dynamic binding model, enhancing the understanding of food protein-enzyme interactions relevant to glycemic regulation.

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谷子蛋白K3ZAN2抑制α-葡萄糖苷酶的机制：实验与分子模拟相结合的研究。

具有α-葡萄糖苷酶抑制活性的膳食蛋白因其支持血糖控制的作用而受到关注。在这里，我们报道了小米衍生的蛋白K3ZAN2通过灵活区域介导的机制调节α-葡萄糖苷酶的活性。K3ZAN2的IC₅₀为4.15 mg/mL，其蛋白质性质经UV光谱和SDS-PAGE证实。分子对接表明，柔性残基Thr11、Ser18、Gln20、Gly26和Gln64通过氢键和疏水相互作用与α-葡萄糖苷酶活性位点残基相互作用。分子动力学模拟（102 ns）表明结构稳定性（RMSD ~ 0.2 nm）、致密性（Rg ~ 1.9 nm）和持久的氢键。结合自由能（ΔG = -15,536.71 kJ/mol）支持强亲和力。主成分分析和自由能分析揭示了构象转变和稳定状态，动态互相关分析揭示了界面上的协调运动。这些计算见解支持动态结合模型，增强了对与血糖调节相关的食物蛋白-酶相互作用的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Food Chemistry: X CHEMISTRY, APPLIED-

CiteScore

4.90

自引率

6.60%

发文量

315

审稿时长

55 days

期刊介绍： Food Chemistry: X, one of three Open Access companion journals to Food Chemistry, follows the same aims, scope, and peer-review process. It focuses on papers advancing food and biochemistry or analytical methods, prioritizing research novelty. Manuscript evaluation considers novelty, scientific rigor, field advancement, and reader interest. Excluded are studies on food molecular sciences or disease cure/prevention. Topics include food component chemistry, bioactives, processing effects, additives, contaminants, and analytical methods. The journal welcome Analytical Papers addressing food microbiology, sensory aspects, and more, emphasizing new methods with robust validation and applicability to diverse foods or regions.