7YG5

Structure of human R-type voltage-gated CaV2.3-alpha2/delta1-beta1 channel complex in the topiramate-bound state

Summary for 7YG5

• Entry DOI: 10.2210/pdb7yg5/pdb
• EMDB information: 33808
• Descriptor: Voltage-dependent R-type calcium channel subunit alpha-1E, [(3aS,5aR,8aR,8bS)-2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxolo[4,5-b:4',5'-d]pyran-3a-yl]methyl sulfamate, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: voltage-gated calcium channel, cav2.3, complex, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 463732.16

Authors

Gao, Y.,Zhao, Y. (deposition date: 2022-07-11, release date: 2023-11-29, Last modification date: 2024-11-13)

Primary citation

Gao, Y.,Bai, Q.,Zhang, X.C.,Zhao, Y.
Structural insights into the allosteric effects of the antiepileptic drug topiramate on the Ca V 2.3 channel.
Biochem.Biophys.Res.Commun., 725:150271-150271, 2024

PubMed Abstract: The R-type voltage-gated calcium channel Ca2.3 is predominantly located in the presynapse and is implicated in distinct types of epileptic seizures. It has consequently emerged as a molecular target in seizure treatment. Here, we determined the cryo-EM structure of the Ca2.3-α2δ1-β1 complex in the topiramate-bound state at a 3.0 Å resolution. We provide a snapshot of the binding site of topiramate, a widely prescribed antiepileptic drug, on a voltage-gated ion channel. The binding site is located at an intracellular juxtamembrane hydrophilic cavity. Further structural analysis revealed that topiramate may allosterically facilitate channel inactivation. These findings provide fundamental insights into the mechanism underlying the inhibitory effect of topiramate on Ca and Na channels, elucidating a previously unseen modulator binding site and thus pointing toward a route for the development of new drugs.

PubMed: 38901222
DOI: 10.1016/j.bbrc.2024.150271

Experimental method

ELECTRON MICROSCOPY (3 Å)