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Yorodumi- PDB-6tp6: Crystal structure of the Orexin-1 receptor in complex with filorexant -
+Open data
-Basic information
Entry | Database: PDB / ID: 6tp6 | ||||||
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Title | Crystal structure of the Orexin-1 receptor in complex with filorexant | ||||||
Components | Orexin receptor type 1 | ||||||
Keywords | MEMBRANE PROTEIN / 7TM / GPCR | ||||||
Function / homology | Function and homology information orexin receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / feeding behavior / peptide hormone binding / neuropeptide signaling pathway / cellular response to hormone stimulus / regulation of cytosolic calcium ion concentration / G protein-coupled receptor activity / peptide binding / G alpha (q) signalling events ...orexin receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / feeding behavior / peptide hormone binding / neuropeptide signaling pathway / cellular response to hormone stimulus / regulation of cytosolic calcium ion concentration / G protein-coupled receptor activity / peptide binding / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of ERK1 and ERK2 cascade / synapse / plasma membrane Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.338 Å | ||||||
Authors | Rappas, M. / Ali, A. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. ...Rappas, M. / Ali, A. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. / Errey, J.C. / Jazayeri, A. / Marshall, F.H. / Mason, J.S. / Mould, R. / Patel, J.C. / Tehan, B.G. / Weir, M. / Christopher, J.A. | ||||||
Funding support | United States, 1items
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Citation | Journal: J.Med.Chem. / Year: 2020 Title: Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis. Authors: Rappas, M. / Ali, A.A.E. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. / Errey, J.C. / Jazayeri, A. / Marshall, F.H. / ...Authors: Rappas, M. / Ali, A.A.E. / Bennett, K.A. / Brown, J.D. / Bucknell, S.J. / Congreve, M. / Cooke, R.M. / Cseke, G. / de Graaf, C. / Dore, A.S. / Errey, J.C. / Jazayeri, A. / Marshall, F.H. / Mason, J.S. / Mould, R. / Patel, J.C. / Tehan, B.G. / Weir, M. / Christopher, J.A. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6tp6.cif.gz | 276.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6tp6.ent.gz | 222.6 KB | Display | PDB format |
PDBx/mmJSON format | 6tp6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6tp6_validation.pdf.gz | 2.6 MB | Display | wwPDB validaton report |
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Full document | 6tp6_full_validation.pdf.gz | 2.6 MB | Display | |
Data in XML | 6tp6_validation.xml.gz | 26 KB | Display | |
Data in CIF | 6tp6_validation.cif.gz | 34.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/tp/6tp6 ftp://data.pdbj.org/pub/pdb/validation_reports/tp/6tp6 | HTTPS FTP |
-Related structure data
Related structure data | 6to7SC 6todC 6tosC 6totC 6tp3C 6tp4C 6tpgC 6tpjC 6tpnC 6tq4C 6tq6C 6tq7C 6tq9C S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Ens-ID: 1
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-Components
-Protein / Sugars , 2 types, 11 molecules AB
#1: Protein | Mass: 41725.891 Da / Num. of mol.: 2 Mutation: E46A I85L V95A R162L N194A L198A Y211A L304V C339A C375W C376W Source method: isolated from a genetically manipulated source Details: filorexant bound in the orthosteric site / Source: (gene. exp.) Homo sapiens (human) / Gene: HCRTR1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O43613 #5: Sugar | ChemComp-SOG / |
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-Non-polymers , 6 types, 61 molecules
#2: Chemical | #3: Chemical | #4: Chemical | ChemComp-SO4 / #6: Chemical | ChemComp-CL / | #7: Chemical | #8: Water | ChemComp-HOH / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 3.87 Å3/Da / Density % sol: 68.24 % |
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Crystal grow | Temperature: 284 K / Method: vapor diffusion, sitting drop / pH: 4.3 Details: 0.1M TRISODIUM CITRATE 50mM SODIUM CHLORIDE 50mM LITHIUM SULPHATE 15-34% PEG400 PH range: 3.0-6.5 / Temp details: Stable |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.96861 Å |
Detector | Type: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jan 13, 2016 |
Radiation | Monochromator: Si (111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.96861 Å / Relative weight: 1 |
Reflection | Resolution: 2.338→34.992 Å / Num. obs: 29373 / % possible obs: 59.95 % / Redundancy: 5.2 % / CC1/2: 0.997 / Net I/σ(I): 13.5 |
Reflection shell | Resolution: 2.338→2.421 Å / Num. unique obs: 90 / CC1/2: 0.486 / % possible all: 2 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 6TO7 Resolution: 2.338→34.992 Å / SU ML: 0.3 / Cross valid method: THROUGHOUT / σ(F): 1.36 / Phase error: 35.47
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 187.14 Å2 / Biso mean: 77.3685 Å2 / Biso min: 24.66 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: final / Resolution: 2.338→34.992 Å
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Refine LS restraints NCS |
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LS refinement shell | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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