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-Structure paper
タイトル | Structural insights into the allosteric effects of the antiepileptic drug topiramate on the Ca2.3 channel. |
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ジャーナル・号・ページ | Biochem Biophys Res Commun, Vol. 725, Page 150271, Year 2024 |
掲載日 | 2024年6月15日 |
![]() | Yiwei Gao / Qinru Bai / Xuejun Cai Zhang / Yan Zhao / ![]() |
PubMed 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 3.0 Å |
構造データ | EMDB-33808, PDB-7yg5: |
化合物 | ![]() ChemComp-Y01: ![]() ChemComp-R16: ![]() ChemComp-3PE: ![]() ChemComp-CA: ![]() ChemComp-TOR: ![]() ChemComp-NAG: |
由来 |
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![]() | MEMBRANE PROTEIN / Voltage-gated calcium channel / CaV2.3 / Complex |