Grifolamine A, a novel bis-γ-butyrolactone from Grifola frondosa exerted inhibitory effect on α-glucosidase and their binding interaction: Affinity and molecular dynamics simulation.
Grifolamine A, a novel bis-γ-butyrolactone from Grifola frondosa exerted inhibitory effect on α-glucosidase and their binding interaction: Affinity and molecular dynamics simulation.
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Grifolamine A，一种来自灰树花的新型双γ-丁内酯，对α-葡萄糖苷酶及其结合相互作用具有抑制作用：亲和力和分子动力学模拟
DOI：
10.1016/j.crfs.2022.10.026
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发表时间：
2022
影响因子：
6.3
通讯作者：
Wu, Qingping
中科院分区：
文献类型：
--
作者：
Chen, Shaodan;Mu, Zhenqiang;Yong, Tianqiao;Gu, Jiangyong;Zhang, Yifan;Gao, Xiong;Xie, Yizhen;Xiao, Chun;Hu, Huiping;Yang, Xiaobing;Li, Xiangmin;Cai, Manjun;Wu, Qingping
关键词：
从灰树花多糖制备的副产物中分离到一种新型γ-丁内酯grifolamine A(1)，这是自然界中首次分离到γ-丁内酯二聚体，同时还分离到3种已知的γ-丁内酯（2-4）。通过广谱分析结合量子化学计算对grifolamine A(1)的结构和立体化学性质进行了研究。提出了化合物1和2-4的生物合成来源。Grifolamine A(1)对α-葡萄糖苷酶有较强的抑制作用。通过表面等离子体共振（SPR）、分子对接、分子动力学（MD）模拟和结合自由能计算揭示了其潜在的抑制机制。SPR结果表明，grifolamine A与α-葡萄糖苷酶具有较强的亲和力，其平衡解离常数（KD）为1.178 × 10−4 m。分子对接表明，grifolamine A通过范德华力、烷基相互作用和碳氢键作用位于α-葡萄糖苷酶的活性口袋中，从而改变了α-葡萄糖苷酶的微环境结构。MD模拟表明，grifolamine A与α-葡萄糖苷酶具有较高的结合亲和力，平均自由能为−25.2±3.2 kcal/mol。自由能分解结果表明，结合袋上的PHE298、PHE308、PHE309、PHE155和ARG310等氨基酸残基对grifolamine a与α-葡萄糖苷酶的相互作用有显著的正影响。本研究结果为基于γ-丁内酯骨架的新型α-葡萄糖苷酶抑制剂的设计和开发提供了有价值的信息。Grifolamine A是首个γ-丁内酯二聚体，从食用蘑菇Grifola frondosa的副产物中分离得到。提出了grifolamine A的生物合成来源。Grifolamine A对α-葡萄糖苷酶具有较强的体外抑制活性。采用表面等离子体共振和分子动力学模拟分析了grifolamine A与α-葡萄糖苷酶的结合。Grifolamine A是一种潜在的营养品，对2型糖尿病具有高血糖作用。
A novel bis-γ-butyrolactone grifolamine A (1), the first γ-butyrolactone dimer from nature, together with three known γ-butyrolactones (2–4), was isolated from the byproduct from Grifola frondosa polysaccharides preparation process. The structure and stereochemistry of grifolamine A (1) were elucidated by extensive spectroscopic analysis combined with quantum chemical calculation. The biosynthetic origin of compound 1, as well as 2–4 was proposed. Grifolamine A (1) showed an intense inhibition against α-glucosidase in vitro. The underlying inhibitory mechanism was revealed by surface plasmon resonance (SPR), molecular docking, molecular dynamics (MD) simulation and binding free energy calculation. SPR revealed that grifolamine A exhibited a strong affinity to α-glucosidase with an equilibrium dissociation constant (KD) value of 1.178 × 10−4 M. Molecular docking manifested that grifolamine A sat at the active pocket of α-glucosidase by van der Waals force, alkyl interaction and carbon hydrogen bonds, and consequently changed the micro-environmental structure of α-glucosidase. MD simulation revealed that grifolamine A had high binding affinity to α-glucosidase with average free energy of −25.2 ± 3.2 kcal/mol. Free energy decomposition indicated amino acid residues including PHE298, PHE308, PHE309, PHE155 and ARG310 at the binding pocket played a strongly positive effect on the interaction between grifolamine A and α-glucosidase. Our findings provide valuable information for the design and development of novel α-glucosidase inhibitors based on γ-butyrolactone skeleton. Grifolamine A, the first γ-butyrolactone dimer, was isolated from the byproduct of the edible mushroom Grifola frondosa. The biosynthetic origin of grifolamine A was proposed. Grifolamine A had strong inhibitory activity against α-glucosidase in vitro. The binding of grifolamine A to α-glucosidase was analyzed by surface plasmon resonance and molecular dynamics simulation. Grifolamine A is a potential nutraceutical with hyperglycemic effect for type 2 diabetes.
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影响因子：
6.3
作者：
Suttithumsatid, Wiwit;Shah, Muhammad Ajmal;Bibi, Shabana;Panichayupakaranant, Pharkphoom
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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