8e5b
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Human L-type voltage-gated calcium channel Cav1.3 in the presence of Amiodarone and Sofosbuvir at 3.3 Angstrom resolution== | |
| + | <StructureSection load='8e5b' size='340' side='right'caption='[[8e5b]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8e5b]] 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=8E5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E5B FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBI:(2-BUTYL-1-BENZOFURAN-3-YL){4-[2-(DIETHYLAMINO)ETHOXY]-3,5-DIIODOPHENYL}METHANONE'>BBI</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</scene>, <scene name='pdbligand=WG6:Sofosbuvir'>WG6</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=8e5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e5b OCA], [https://pdbe.org/8e5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e5b RCSB], [https://www.ebi.ac.uk/pdbsum/8e5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e5b ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CA2D1_HUMAN CA2D1_HUMAN] Familial short QT syndrome;Brugada syndrome. | ||
| + | == 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. Plays an important role in excitation-contraction coupling (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Drug-drug interaction of the antiviral sofosbuvir and the antiarrhythmics amiodarone has been reported to cause fatal heartbeat slowing. Sofosbuvir and its analog, MNI-1, were reported to potentiate the inhibition of cardiomyocyte calcium handling by amiodarone, which functions as a multi-channel antagonist, and implicate its inhibitory effect on L-type Ca(v) channels, but the molecular mechanism has remained unclear. Here we present systematic cryo-EM structural analysis of Ca(v)1.1 and Ca(v)1.3 treated with amiodarone or sofosbuvir alone, or sofosbuvir/MNI-1 combined with amiodarone. Whereas amiodarone alone occupies the dihydropyridine binding site, sofosbuvir is not found in the channel when applied on its own. In the presence of amiodarone, sofosbuvir/MNI-1 is anchored in the central cavity of the pore domain through specific interaction with amiodarone and directly obstructs the ion permeation path. Our study reveals the molecular basis for the physical, pharmacodynamic interaction of two drugs on the scaffold of Ca(v) channels. | ||
| - | + | Structural basis for the severe adverse interaction of sofosbuvir and amiodarone on L-type Ca(v) channels.,Yao X, Gao S, Wang J, Li Z, Huang J, Wang Y, Wang Z, Chen J, Fan X, Wang W, Jin X, Pan X, Yu Y, Lagrutta A, Yan N Cell. 2022 Nov 17:S0092-8674(22)01370-8. doi: 10.1016/j.cell.2022.10.024. PMID:36417914<ref>PMID:36417914</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Gao | + | <div class="pdbe-citations 8e5b" style="background-color:#fffaf0;"></div> |
| - | [[Category: Yan | + | == References == |
| - | [[Category: Yao | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Gao S]] | ||
| + | [[Category: Yan N]] | ||
| + | [[Category: Yao X]] | ||
Revision as of 08:21, 7 December 2022
Human L-type voltage-gated calcium channel Cav1.3 in the presence of Amiodarone and Sofosbuvir at 3.3 Angstrom resolution
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Categories: Homo sapiens | Large Structures | Gao S | Yan N | Yao X
