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6kzp

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calcium channel-ligand

6kzp, resolution 3.10Å

Structural highlights

6kzp is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	CACNA1G, KIAA1123 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CAC1G_HUMAN] Spinocerebellar ataxia type 42. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.

Function

[CAC1G_HUMAN] Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Among the ten subtypes of mammalian voltage-gated calcium (Cav) channels, Cav3.1-Cav3.3 constitute the T-type, or the low-voltage-activated, subfamily, the abnormal activities of which are associated with epilepsy, psychiatric disorders and pain(1-5). Here we report the cryo-electron microscopy structures of human Cav3.1 alone and in complex with a highly Cav3-selective blocker, Z944(6,7), at resolutions of 3.3 A and 3.1 A, respectively. The arch-shaped Z944 molecule reclines in the central cavity of the pore domain, with the wide end inserting into the fenestration on the interface between repeats II and III, and the narrow end hanging above the intracellular gate like a plug. The structures provide the framework for comparative investigation of the distinct channel properties of different Cav subfamilies.

Cryo-EM structures of apo and antagonist-bound human Cav3.1.,Zhao Y, Huang G, Wu Q, Wu K, Li R, Lei J, Pan X, Yan N Nature. 2019 Nov 25. pii: 10.1038/s41586-019-1801-3. doi:, 10.1038/s41586-019-1801-3. PMID:31766050^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cribbs LL, Gomora JC, Daud AN, Lee JH, Perez-Reyes E. Molecular cloning and functional expression of Ca(v)3.1c, a T-type calcium channel from human brain. FEBS Lett. 2000 Jan 21;466(1):54-8. doi: 10.1016/s0014-5793(99)01756-1. PMID:10648811 doi:http://dx.doi.org/10.1016/s0014-5793(99)01756-1
↑ Monteil A, Chemin J, Bourinet E, Mennessier G, Lory P, Nargeot J. Molecular and functional properties of the human alpha(1G) subunit that forms T-type calcium channels. J Biol Chem. 2000 Mar 3;275(9):6090-100. PMID:10692398
↑ Coutelier M, Blesneac I, Monteil A, Monin ML, Ando K, Mundwiller E, Brusco A, Le Ber I, Anheim M, Castrioto A, Duyckaerts C, Brice A, Durr A, Lory P, Stevanin G. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia. Am J Hum Genet. 2015 Nov 5;97(5):726-37. doi: 10.1016/j.ajhg.2015.09.007. Epub, 2015 Oct 8. PMID:26456284 doi:http://dx.doi.org/10.1016/j.ajhg.2015.09.007
↑ Morino H, Matsuda Y, Muguruma K, Miyamoto R, Ohsawa R, Ohtake T, Otobe R, Watanabe M, Maruyama H, Hashimoto K, Kawakami H. A mutation in the low voltage-gated calcium channel CACNA1G alters the physiological properties of the channel, causing spinocerebellar ataxia. Mol Brain. 2015 Dec 29;8:89. doi: 10.1186/s13041-015-0180-4. PMID:26715324 doi:http://dx.doi.org/10.1186/s13041-015-0180-4
↑ Chemin J, Siquier-Pernet K, Nicouleau M, Barcia G, Ahmad A, Medina-Cano D, Hanein S, Altin N, Hubert L, Bole-Feysot C, Fourage C, Nitschke P, Thevenon J, Rio M, Blanc P, Vidal C, Bahi-Buisson N, Desguerre I, Munnich A, Lyonnet S, Boddaert N, Fassi E, Shinawi M, Zimmerman H, Amiel J, Faivre L, Colleaux L, Lory P, Cantagrel V. De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene. Brain. 2018 Jul 1;141(7):1998-2013. doi: 10.1093/brain/awy145. PMID:29878067 doi:http://dx.doi.org/10.1093/brain/awy145
↑ Zhao Y, Huang G, Wu Q, Wu K, Li R, Lei J, Pan X, Yan N. Cryo-EM structures of apo and antagonist-bound human Cav3.1. Nature. 2019 Nov 25. pii: 10.1038/s41586-019-1801-3. doi:, 10.1038/s41586-019-1801-3. PMID:31766050 doi:http://dx.doi.org/10.1038/s41586-019-1801-3

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6kzp"

@@ Line 1: / Line 1: @@
 ==calcium channel-ligand==
-<StructureSection load='6kzp' size='340' side='right'caption='[[6kzp]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+<SX load='6kzp' size='340' side='right' viewer='molstar' caption='[[6kzp]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6kzp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KZP FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6kzp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KZP OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KZP FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DZR:~{N}-[[1-[2-(~{tert}-butylamino)-2-oxidanylidene-ethyl]piperidin-4-yl]methyl]-3-chloranyl-5-fluoranyl-benzamide'>DZR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
+</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=DZR:~{N}-[[1-[2-(~{tert}-butylamino)-2-oxidanylidene-ethyl]piperidin-4-yl]methyl]-3-chloranyl-5-fluoranyl-benzamide'>DZR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CACNA1G, KIAA1123 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kzp OCA], [http://pdbe.org/6kzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kzp RCSB], [http://www.ebi.ac.uk/pdbsum/6kzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kzp ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kzp OCA], [http://pdbe.org/6kzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kzp RCSB], [http://www.ebi.ac.uk/pdbsum/6kzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kzp ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 24: / Line 24: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Human]]
 [[Category: Large Structures]]

6kzp

From Proteopedia

Current revision

calcium channel-ligand

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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