<br>通过基于肽转运蛋白 1 (PepT1) 激活的分子对接虚拟筛选豌豆蛋白水解物中的 GLP-1 分泌肽,Journal of Agricultural and Food Chemistry

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通过基于肽转运蛋白 1 (PepT1) 激活的分子对接虚拟筛选豌豆蛋白水解物中的 GLP-1 分泌肽
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-06-07 , DOI: 10.1021/acs.jafc.4c00999
Mingkai Zhang ₁ , Ling Zhu ₁ , Hui Zhang ₁ , Xingguo Wang ₁ , Tongtong Liu ₁ , Gangcheng Wu ₁

Affiliation

膳食蛋白通过肠道蛋白感应诱导胰高血糖素样肽 1 (GLP-1) 分泌来调节葡萄糖稳态。然而，来自膳食蛋白质的GLP-1分泌肽的报道很少，并且通过传统分离和纯化方法鉴定GLP-1分泌肽的研究是费力的。在此，我们通过肽组分析和与肽转运蛋白 1 (PepT1) 的分子对接，快速虚拟筛选了豌豆蛋白水解物 (PPH) 中的两种 GLP-1 分泌肽。添加 PepT1 拮抗剂 4-氨基苯甲酸 (4-AMBA) 后，PPH 刺激的 GLP-1 分泌减少，表明 PepT1 激活参与了 NCI-H716 细胞中 PPH 诱导的 GLP-1 分泌。随后，通过肽组分析获得了PPHs中的307个三肽。其中，通过基于 PepT1 激活的分子对接鉴定出两种 GLP-1 分泌肽 FLR 和 LRW。 FLR 和 LRW (1 mg/mL) 使 GLP-1 水平分别增加至 170.20% ± 27.83% 和 272.37% ± 45.96% (p < 0.05)。更重要的是，分子对接表明肽与 PepT1 活性中心（特别是 N 袋中的 Glu595、Asn329 和 Asn171 以及 C 袋中的 Arg27）之间的相互作用对于刺激 GLP-1 分泌的肽活性至关重要。我们的研究表明，肽组学和基于 PepT1 激活的分子对接相结合是鉴定 GLP-1 分泌肽的一种有前途的方法。

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Virtual Screening of GLP-1-Secreting Peptides from Pea Protein Hydrolysates via Peptide Transporter 1 (PepT1) Activation-Based Molecular Docking

Dietary proteins regulate glucose homeostasis via intestinal protein sensing-induced glucagon-like peptide 1 (GLP-1) secretion. However, the reported GLP-1-secreting peptides derived from dietary proteins are few, and studies regarding GLP-1-secreting peptide identification by traditional separation and purification methods are laborious. Herein, we have rapidly virtual-screened two GLP-1 secreting peptides from pea protein hydrolysates (PPHs) by peptidomic analysis and molecular docking with peptide transporter 1 (PepT1). PPH-stimulated GLP-1 secretion decreased after adding the PepT1 antagonist 4-aminobenzoic acid (4-AMBA), indicating that PepT1 activation was involved in PPH-induced GLP-1 secretion in NCI-H716 cells. Subsequently, 307 tripeptides in PPHs were obtained through peptidomic analysis. Among them, two GLP-1-secreting peptides, FLR and LRW, were identified via PepT1 activation-based molecular docking. FLR and LRW (1 mg/mL) increased GLP-1 levels to 170.20% ± 27.83% and 272.37% ± 45.96%, respectively (p < 0.05). More importantly, molecular docking implied that the interactions between peptides and the active center of PepT1 (especially Glu595, Asn329, and Asn171 in the N-pocket and Arg27 in the C-pocket) were crucial for peptide activity in stimulating GLP-1 secretion. Our study suggested that the combination of peptidomics and PepT1 activation-based molecular docking is a promising approach for identification of GLP-1-secreting peptides.

更新日期：2024-06-07

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