Quinidine partially blocks mitochondrial voltage-dependent anion channel (VDAC).
Animals
Anions
Crystallography, X-Ray
Cysteine
/ chemistry
Female
Glutamic Acid
/ chemistry
Inhibitory Concentration 50
Male
Mitochondria
/ metabolism
Molecular Docking Simulation
Neurons
/ metabolism
Oxidative Phosphorylation
Protein Structure, Secondary
Quinidine
/ pharmacology
Rats
Rats, Wistar
Spectrometry, Fluorescence
Voltage-Dependent Anion Channel 1
/ chemistry
Voltage-Dependent Anion Channel 2
/ chemistry
Bilayer electrophysiology
Bilayer membrane (BLM)
Docking
Fluorescence spectroscopy
Quinidine
Voltage-dependent anion channel (VDAC)
Journal
European biophysics journal : EBJ
ISSN: 1432-1017
Titre abrégé: Eur Biophys J
Pays: Germany
ID NLM: 8409413
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
24
11
2019
accepted:
17
02
2020
revised:
12
02
2020
pubmed:
11
3
2020
medline:
15
12
2020
entrez:
11
3
2020
Statut:
ppublish
Résumé
Quinidine is an antiarrhythmic drug commonly used for the treatment of cardiac ailments. It affects oxidative phosphorylation, calcium uptake, and ion channels of mitochondria. We have investigated the interaction of Quinidine and mitochondrial voltage-dependent anion channel (VDAC). VDAC was purified from neuronal tissue of Wistar rats and in vitro bilayer electrophysiology experiments were performed on it. 50-mM Quinidine treatment on VDAC leads to a sudden drop in its conductance. The dose of Quinidine leading to a half-maximal current through a single-channel VDAC was calculated using Quinidine at different concentrations. In silico molecular docking studies using Autodock-4.2 software indicate interaction between Quinidine and VDAC. Docking results demonstrate the interaction of Quinidine and VDAC on its Glutamic acid residue (Glu-206 of VDAC). Fluorescence spectroscopy results on Quinidine and Glutamic acid interaction show an increase in the intensity and wavelength of Quinidine fluorescence, whereas no interaction between Quinidine and Cysteine was observed. This further supports the Glutamic acid and Quinidine interaction. In conclusion, we report Quinidine partially blocks VDAC due to the interaction of Glutamic acid and Quinidine in the channel pore.
Identifiants
pubmed: 32152682
doi: 10.1007/s00249-020-01426-z
pii: 10.1007/s00249-020-01426-z
doi:
Substances chimiques
Anions
0
Vdac1 protein, rat
0
Vdac2 protein, rat
0
Voltage-Dependent Anion Channel 2
0
Glutamic Acid
3KX376GY7L
Voltage-Dependent Anion Channel 1
EC 1.6.-
Quinidine
ITX08688JL
Cysteine
K848JZ4886
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
193-205Références
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