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Open data
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Basic information
Entry | Database: PDB / ID: 6jp5 | |||||||||||||||||||||
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Title | Rabbit Cav1.1-Nifedipine Complex | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / Membrane protein complex modulated by FDA approved drug. | |||||||||||||||||||||
Function / homology | ![]() positive regulation of muscle contraction / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / cellular response to caffeine / calcium ion import across plasma membrane / calcium channel regulator activity / regulation of ryanodine-sensitive calcium-release channel activity / voltage-gated calcium channel activity / muscle contraction ...positive regulation of muscle contraction / high voltage-gated calcium channel activity / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / cellular response to caffeine / calcium ion import across plasma membrane / calcium channel regulator activity / regulation of ryanodine-sensitive calcium-release channel activity / voltage-gated calcium channel activity / muscle contraction / release of sequestered calcium ion into cytosol / T-tubule / calcium ion transmembrane transport / sarcolemma / transmembrane transporter binding / calmodulin binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||
![]() | Zhao, Y. / Huang, G. / Wu, J. / Yan, N. | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular Basis for Ligand Modulation of a Mammalian Voltage-Gated Ca Channel. Authors: Yanyu Zhao / Gaoxingyu Huang / Jianping Wu / Qiurong Wu / Shuai Gao / Zhen Yan / Jianlin Lei / Nieng Yan / ![]() ![]() Abstract: The L-type voltage-gated Ca (Ca) channels are modulated by various compounds exemplified by 1,4-dihydropyridines (DHP), benzothiazepines (BTZ), and phenylalkylamines (PAA), many of which have been ...The L-type voltage-gated Ca (Ca) channels are modulated by various compounds exemplified by 1,4-dihydropyridines (DHP), benzothiazepines (BTZ), and phenylalkylamines (PAA), many of which have been used for characterizing channel properties and for treatment of hypertension and other disorders. Here, we report the cryoelectron microscopy (cryo-EM) structures of Ca1.1 in complex with archetypal antagonistic drugs, nifedipine, diltiazem, and verapamil, at resolutions of 2.9 Å, 3.0 Å, and 2.7 Å, respectively, and with a DHP agonist Bay K 8644 at 2.8 Å. Diltiazem and verapamil traverse the central cavity of the pore domain, directly blocking ion permeation. Although nifedipine and Bay K 8644 occupy the same fenestration site at the interface of repeats III and IV, the coordination details support previous functional observations that Bay K 8644 is less favored in the inactivated state. These structures elucidate the modes of action of different Ca ligands and establish a framework for structure-guided drug discovery. | |||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 530.4 KB | Display | ![]() |
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PDB format | ![]() | 407.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 9866MC ![]() 9867C ![]() 9868C ![]() 9869C ![]() 6jp8C ![]() 6jpaC ![]() 6jpbC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Voltage-dependent L-type calcium channel subunit ... , 2 types, 3 molecules ABC
#1: Protein | Mass: 212240.594 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#4: Protein | Mass: 49642.430 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
-Voltage-dependent calcium channel ... , 2 types, 2 molecules EF
#2: Protein | Mass: 25082.254 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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#3: Protein | Mass: 121675.938 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
-Sugars , 3 types, 16 molecules ![](data/chem/img/NAG.gif)
#5: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose Source method: isolated from a genetically manipulated source #6: Polysaccharide | Source method: isolated from a genetically manipulated source #7: Sugar | ChemComp-NAG / |
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-Non-polymers , 5 types, 14 molecules ![](data/chem/img/CA.gif)
![](data/chem/img/3PE.gif)
![](data/chem/img/C5U.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/ETA.gif)
![](data/chem/img/3PE.gif)
![](data/chem/img/C5U.gif)
![](data/chem/img/PC1.gif)
![](data/chem/img/ETA.gif)
#8: Chemical | #9: Chemical | ChemComp-3PE / #10: Chemical | ChemComp-C5U / | #11: Chemical | ChemComp-PC1 / | #12: Chemical | ChemComp-ETA / | |
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-Details
Sequence details | As for the unusual connection between Y619-S621 of Chain F, the original amino acid for S620 is ...As for the unusual connection between Y619-S621 of Chain F, the original amino acid for S620 is Y620 and the density for this large side chain is missing from reconstruction. Authors suspect this to be a result of alternative splicing. The density in this beta strand, Y619 and S621, is very clear and allows accurate side chain assignment for this area and surrounding areas. |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component |
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Molecular weight | Units: KILODALTONS/NANOMETER / Experimental value: NO | ||||||||||||||||||
Source (natural) | Organism: ![]() ![]() | ||||||||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 48 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Quantum LS / Energyfilter slit width: 20 eV |
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Processing
CTF correction | Type: PHASE FLIPPING ONLY |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 245171 / Symmetry type: POINT |