View source for 8we9


==Human L-type voltage-gated calcium channel Cav1.2 (Class I) in the presence of pinaverium at 3.0 Angstrom resolution==
<StructureSection load='8we9' size='340' side='right'caption='[[8we9]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8we9]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8WE9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WE9 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PT5:(1S)-2-{[(R)-HYDROXY{[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIHYDROXY-4,5-BIS(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL]OXY}-1-[(OCTADECANOYLOXY)METHYL]ETHYL+(8E,11E)-ICOSA-5,8,11,14-TETRAENOATE'>PT5</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8we9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8we9 OCA], [https://pdbe.org/8we9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8we9 RCSB], [https://www.ebi.ac.uk/pdbsum/8we9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8we9 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CA2D1_HUMAN 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 ==
[https://www.uniprot.org/uniprot/CA2D1_HUMAN 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).<ref>PMID:35293990</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ca(v)1.2 channels play crucial roles in various neuronal and physiological processes. Here, we present cryo-EM structures of human Ca(v)1.2, both in its apo form and in complex with several drugs, as well as the peptide neurotoxin calciseptine. Most structures, apo or bound to calciseptine, amlodipine, or a combination of amiodarone and sofosbuvir, exhibit a consistent inactivated conformation with a sealed gate, three up voltage-sensing domains (VSDs), and a down VSD(II). Calciseptine sits on the shoulder of the pore domain, away from the permeation path. In contrast, when pinaverium bromide, an antispasmodic drug, is inserted into a cavity reminiscent of the IFM-binding site in Na(v) channels, a series of structural changes occur, including upward movement of VSD(II) coupled with dilation of the selectivity filter and its surrounding segments in repeat III. Meanwhile, S4-5(III) merges with S5(III) to become a single helix, resulting in a widened but still non-conductive intracellular gate.

Structural basis for human Ca(v)1.2 inhibition by multiple drugs and the neurotoxin calciseptine.,Gao S, Yao X, Chen J, Huang G, Fan X, Xue L, Li Z, Wu T, Zheng Y, Huang J, Jin X, Wang Y, Wang Z, Yu Y, Liu L, Pan X, Song C, Yan N Cell. 2023 Nov 22;186(24):5363-5374.e16. doi: 10.1016/j.cell.2023.10.007. Epub , 2023 Nov 15. PMID:37972591<ref>PMID:37972591</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8we9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Fan X]]
[[Category: Gao S]]
[[Category: Yan N]]
[[Category: Yao X]]