Structural highlights
7yg5 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Method: | Electron Microscopy, Resolution 3Å |
| Ligands: | , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
CA2D1_HUMAN Familial short QT syndrome;Non-specific early-onset epileptic encephalopathy;Brugada syndrome. The disease is caused by variants affecting the gene represented in this entry.
Function
CA2D1_HUMAN The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (PubMed:35293990). Plays an important role in excitation-contraction coupling (By similarity).[1]
Publication Abstract from PubMed
The R-type voltage-gated calcium channel Ca(V)2.3 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 Ca(V)2.3-alpha2delta1-beta1 complex in the topiramate-bound state at a 3.0 A 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(V) and Na(V) channels, elucidating a previously unseen modulator binding site and thus pointing toward a route for the development of new drugs.
Structural insights into the allosteric effects of the antiepileptic drug topiramate on the Ca(V)2.3 channel.,Gao Y, Bai Q, Zhang XC, Zhao Y Biochem Biophys Res Commun. 2024 Jun 15;725:150271. doi: , 10.1016/j.bbrc.2024.150271. PMID:38901222[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dahimene S, von Elsner L, Holling T, Mattas LS, Pickard J, Lessel D, Pilch KS, Kadurin I, Pratt WS, Zhulin IB, Dai H, Hempel M, Ruzhnikov MRZ, Kutsche K, Dolphin AC. Biallelic CACNA2D1 loss-of-function variants cause early-onset developmental epileptic encephalopathy. Brain. 2022 Aug 27;145(8):2721-2729. PMID:35293990 doi:10.1093/brain/awac081
- ↑ Gao Y, Bai Q, Zhang XC, Zhao Y. Structural insights into the allosteric effects of the antiepileptic drug topiramate on the Ca(V)2.3 channel. Biochem Biophys Res Commun. 2024 Jun 15;725:150271. PMID:38901222 doi:10.1016/j.bbrc.2024.150271
