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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
- Source :
- Current Research in Food Science, Vol 5, Iss , Pp 2045-2052 (2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 26659271
- Volume :
- 5
- Issue :
- 2045-2052
- Database :
- Directory of Open Access Journals
- Journal :
- Current Research in Food Science
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.b5f067173c1447f98316b956f91d313d
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.crfs.2022.10.026