Binding Site

Site1~8: Up to now, eight binding sites, which can interact with natural toxins and therapeutic drug molecules, have been identified in the structures of VGSCs, and exhibit diverse physiological functions in response to different ligands.
VSD: The VSD (voltage-sensing domain) is the important part of VGSCs, which can sense the change of external voltage and adjust the opening of channel when the membrane is depolarized. The eukaryotic VGSCs have four VSDs (VSDI~VSDIV). In recent years, the fourth VSD (VSDIV) has been determined as a new binding domain and several compounds targeting this domain have entered clinical trials.
✔ In VGSC-DB, the binding site information of compounds are supplemented according to the above domain.


Site Ligand Type Binding domain
1 Tetrodotoxin (TTX), saxitoxin (STX), μ-contoxins Extracellular pore blocker DI~DIV P-loops
2 Batrachotoxin (BTX), veratridine (VTD), grayanotoxin (GTX), aconitine (ACT) Intracellular pore gating activator (state dependent) Near DI~DIV S6 (four repeats)
3 α-scorpion toxins, sea anemone toxins Extracellular gating activator Extracellular loops of DIV S3~S4
4 β-conotoxin, δ-palutoxins, spider toxins Extracellular gating blocker Extracellular loops of DII S1~S2 and S3~S4
5 Ciguatoxins (CTX), brevetoxins (PbTxs) Intracellular pore gating activator (state dependent) Near DI-S6 and DIV-S5
6 δ-conotoxins Extracellular gating activator Near DIV-S4
7 Pyrethroids Intracellular gating activator Near DIII-S6
8 Small-molecule drugs, local anesthetics (LA) LA binding site Near DI~DIV S6
Biological Activity
✔ To help users distinguish the biological activity, the EC50 value is indicated by '*' in the upper right corner of the number.

Search
Find Compound: VGSC-DB can be queried with two general approaches: text-based (i.e., compound's PubChem CID and IUPAC Name) and structure-based search (i.e., input SMILES, draw structure, upload SDF/MOL files).


Advanced Search: VGSC-DB provides a function for advanced searches. A large number of compounds can be searched by selecting the molecular weight, SMILES length, organism, and (IC50). Users can download data in batches.


Results: The search results are displayed in the form of small cards. Users can view the brief information of compound and click the 'VGSC-DB ID' to jump to the compound page.

Data

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