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==Cryo-EM structure of human high-voltage activated L-type calcium channel CaV1.2 in complex with benidipine (BEN)==
<StructureSection load='8hmb' size='340' side='right'caption='[[8hmb]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8hmb]] 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=8HMB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HMB 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]] 3.3&#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=A1AC8:[3-[(4~{R})-3-methoxycarbonyl-2,6-dimethyl-5-[(3~{R})-1-(phenylmethyl)piperidin-3-yl]oxycarbonyl-1,4-dihydropyridin-4-yl]phenyl]-oxidanyl-oxidanylidene-azanium'>A1AC8</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=R16:HEXADECANE'>R16</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=8hmb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hmb OCA], [https://pdbe.org/8hmb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hmb RCSB], [https://www.ebi.ac.uk/pdbsum/8hmb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hmb ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The voltage-gated calcium channel Ca(V)1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of Ca(V)1.2 are involved in brain and heart diseases. Pharmacological inhibition of Ca(V)1.2 is therefore of therapeutic value. Here, we report cryo-EM structures of Ca(V)1.2 in the absence or presence of the antirheumatic drug tetrandrine or antihypertensive drug benidipine. Tetrandrine acts as a pore blocker in a pocket composed of S6(II), S6(III), and S6(IV) helices and forms extensive hydrophobic interactions with Ca(V)1.2. Our structure elucidates that benidipine is located in the D(III)-D(IV) fenestration site. Its hydrophobic sidechain, phenylpiperidine, is positioned at the exterior of the pore domain and cradled within a hydrophobic pocket formed by S5(DIII), S6(DIII), and S6(DIV) helices, providing additional interactions to exert inhibitory effects on both L-type and T-type voltage gated calcium channels. These findings provide the structural foundation for the rational design and optimization of therapeutic inhibitors of voltage-gated calcium channels.

Structural bases of inhibitory mechanism of Ca(V)1.2 channel inhibitors.,Wei Y, Yu Z, Wang L, Li X, Li N, Bai Q, Wang Y, Li R, Meng Y, Xu H, Wang X, Dong Y, Huang Z, Zhang XC, Zhao Y Nat Commun. 2024 Mar 30;15(1):2772. doi: 10.1038/s41467-024-47116-8. PMID:38555290<ref>PMID:38555290</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8hmb" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wei Y]]
[[Category: Yu Z]]
[[Category: Zhao Y]]