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Yorodumi- PDB-7jpx: Rabbit Cav1.1 in the presence of 100 micromolar amlodipine in nan... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7jpx | ||||||
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Title | Rabbit Cav1.1 in the presence of 100 micromolar amlodipine in nanodiscs at 2.9 Angstrom resolution | ||||||
Components |
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Keywords | TRANSPORT PROTEIN / rCav1.1 / Channels / Calcium Ion-Selective / drugs | ||||||
Function / homology | Function and homology information positive regulation of muscle contraction / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / cellular response to caffeine / calcium channel regulator activity / calcium ion import across plasma membrane / voltage-gated calcium channel activity / release of sequestered calcium ion into cytosol / regulation of ryanodine-sensitive calcium-release channel activity / T-tubule ...positive regulation of muscle contraction / L-type voltage-gated calcium channel complex / regulation of calcium ion transmembrane transport via high voltage-gated calcium channel / cellular response to caffeine / calcium channel regulator activity / calcium ion import across plasma membrane / voltage-gated calcium channel activity / release of sequestered calcium ion into cytosol / regulation of ryanodine-sensitive calcium-release channel activity / T-tubule / muscle contraction / calcium ion transmembrane transport / sarcolemma / calcium channel activity / transmembrane transporter binding / calmodulin binding / metal ion binding / plasma membrane Similarity search - Function | ||||||
Biological species | Oryctolagus cuniculus (rabbit) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.9 Å | ||||||
Authors | Yan, N. / Gao, S. | ||||||
Funding support | United States, 1items
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Citation | Journal: Angew Chem Int Ed Engl / Year: 2021 Title: Structural Basis of the Modulation of the Voltage-Gated Calcium Ion Channel Ca 1.1 by Dihydropyridine Compounds*. Authors: Shuai Gao / Nieng Yan / Abstract: 1,4-Dihydropyridines (DHP), the most commonly used antihypertensives, function by inhibiting the L-type voltage-gated Ca (Ca ) channels. DHP compounds exhibit chirality-specific antagonistic or ...1,4-Dihydropyridines (DHP), the most commonly used antihypertensives, function by inhibiting the L-type voltage-gated Ca (Ca ) channels. DHP compounds exhibit chirality-specific antagonistic or agonistic effects. The structure of rabbit Ca 1.1 bound to an achiral drug nifedipine reveals the general binding mode for DHP drugs, but the molecular basis for chiral specificity remained elusive. Herein, we report five cryo-EM structures of nanodisc-embedded Ca 1.1 in the presence of the bestselling drug amlodipine, a DHP antagonist (R)-(+)-Bay K8644, and a titration of its agonistic enantiomer (S)-(-)-Bay K8644 at resolutions of 2.9-3.4 Å. The amlodipine-bound structure reveals the molecular basis for the high efficacy of the drug. All structures with the addition of the Bay K8644 enantiomers exhibit similar inactivated conformations, suggesting that (S)-(-)-Bay K8644, when acting as an agonist, is insufficient to lock the activated state of the channel for a prolonged duration. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7jpx.cif.gz | 435.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7jpx.ent.gz | 350 KB | Display | PDB format |
PDBx/mmJSON format | 7jpx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jp/7jpx ftp://data.pdbj.org/pub/pdb/validation_reports/jp/7jpx | HTTPS FTP |
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-Related structure data
Related structure data | 22426MC 7jpkC 7jplC 7jpvC 7jpwC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
Other databases |
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-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 1 types, 1 molecules A
#1: Protein | Mass: 212240.594 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: P07293 |
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-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) Oryctolagus cuniculus (rabbit) / References: UniProt: P19518 |
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#3: Protein | Mass: 125082.906 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Oryctolagus cuniculus (rabbit) / References: UniProt: P13806 |
-Non-polymers , 5 types, 13 molecules
#4: Chemical | ChemComp-CA / | ||||||
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#5: Chemical | ChemComp-3PE / #6: Chemical | ChemComp-PC1 / | #7: Chemical | ChemComp-POV / ( | #8: Chemical | ChemComp-6UB / | |
-Details
Has ligand of interest | Y |
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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 |
-Sample preparation
Component | Name: rCav1.1-100A / Type: COMPLEX / Entity ID: #1-#3 / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Oryctolagus cuniculus (rabbit) |
Buffer solution | pH: 8 |
Specimen | Conc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: rCav1.1-100A was in lipid nanodisc |
Specimen support | Details: unspecified |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K / Details: blot for 5 seconds before plunging |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.17rc2_3619: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 184373 / Symmetry type: POINT | ||||||||||||||||||||||||
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