Molecular docking and biochemical validation of (-)-syringaresinol-4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside binding to an allosteric site in monoamine transporters

Albizia julibrissin Durazz is one of the most common herbs used for depression and anxiety treatment, but its mechanism of action as an antidepressant or anxiolytic drug have not been fully understood. We previously isolated and identified one lignan glycoside compound from Albizia Julibrissin Duraz...

Full description

Saved in:
Bibliographic Details
Main Authors: Hanhe Liu (Author), Yingyao Wu (Author), Chan Li (Author), Qingfa Tang (Author), Yuan-Wei Zhang (Author)
Format: Book
Published: Frontiers Media S.A., 2022-10-01T00:00:00Z.
Subjects:
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!

MARC

LEADER 00000 am a22000003u 4500
001 doaj_e15cfe93989c41fc9ffc1a00c7fcbb4c
042 |a dc 
100 1 0 |a Hanhe Liu  |e author 
700 1 0 |a Yingyao Wu  |e author 
700 1 0 |a Chan Li  |e author 
700 1 0 |a Qingfa Tang  |e author 
700 1 0 |a Qingfa Tang  |e author 
700 1 0 |a Yuan-Wei Zhang  |e author 
245 0 0 |a Molecular docking and biochemical validation of (-)-syringaresinol-4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside binding to an allosteric site in monoamine transporters 
260 |b Frontiers Media S.A.,   |c 2022-10-01T00:00:00Z. 
500 |a 1663-9812 
500 |a 10.3389/fphar.2022.1018473 
520 |a Albizia julibrissin Durazz is one of the most common herbs used for depression and anxiety treatment, but its mechanism of action as an antidepressant or anxiolytic drug have not been fully understood. We previously isolated and identified one lignan glycoside compound from Albizia Julibrissin Durazz, (-)-syringaresinol-4-O-β-D-apiofuranosyl-(1→2)-β-D-glucopyranoside (SAG), that inhibited all three monoamine transporters with a mechanism of action different from that of the conventional antidepressants. In this study, we generated homology models for human dopamine transporter and human norepinephrine transporter, based on the X-ray structure of Drosophila dopamine transporter, and conducted the molecular docking of SAG to all three human monoamine transporters. Our computational results indicated that SAG binds to an allosteric site (S2) that has been demonstrated to be formed by an aromatic pocket positioned in the scaffold domain in the extracellular vestibule connected to the central site (S1) in these monoamine transporters. In addition, we demonstrated that SAG stabilizes a conformation of serotonin transporter with both the extracellular and cytoplasmic pathways closed. Furthermore, we performed mutagenesis of the residues in both the allosteric and orthosteric sites to biochemically validate SAG binding in all three monoamine transporters. Our results are consistent with the molecular docking calculation and support the association of SAG with the allosteric site. We expect that this herbal molecule could become a lead compound for the development of new therapeutic agents with a novel mechanism of action. 
546 |a EN 
690 |a Albizia julibrissin 
690 |a antidepressants 
690 |a mechanism of action 
690 |a serotonin transporter 
690 |a monoamine transporters 
690 |a molecular docking 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Frontiers in Pharmacology, Vol 13 (2022) 
787 0 |n https://www.frontiersin.org/articles/10.3389/fphar.2022.1018473/full 
787 0 |n https://doaj.org/toc/1663-9812 
856 4 1 |u https://doaj.org/article/e15cfe93989c41fc9ffc1a00c7fcbb4c  |z Connect to this object online.