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Yorodumi- PDB-8ax6: Crystal structure of a CGRP receptor ectodomain heterodimer bound... -
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-Basic information
Entry | Database: PDB / ID: 8ax6 | ||||||
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Title | Crystal structure of a CGRP receptor ectodomain heterodimer bound to macrocyclic inhibitor HTL0029882 | ||||||
Components | Maltose/maltodextrin-binding periplasmic protein,Receptor activity-modifying protein 1,Calcitonin gene-related peptide type 1 receptor | ||||||
Keywords | MEMBRANE PROTEIN / CGRP / CGRPR / ectodomain / RAMP / macrocycle / macrocyclic | ||||||
Function / homology | Function and homology information calcitonin gene-related peptide binding / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / adrenomedullin binding / positive regulation of protein glycosylation / cellular response to sucrose stimulus / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / amylin receptor activity ...calcitonin gene-related peptide binding / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / adrenomedullin binding / positive regulation of protein glycosylation / cellular response to sucrose stimulus / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / amylin receptor activity / calcitonin receptor activity / vascular associated smooth muscle cell proliferation / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway / Calcitonin-like ligand receptors / regulation of G protein-coupled receptor signaling pathway / detection of maltose stimulus / maltose transport complex / carbohydrate transport / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / carbohydrate transmembrane transporter activity / maltose binding / maltose transport / maltodextrin transmembrane transport / coreceptor activity / ATP-binding cassette (ABC) transporter complex, substrate-binding subunit-containing / cellular response to hormone stimulus / positive regulation of vascular associated smooth muscle cell proliferation / ATP-binding cassette (ABC) transporter complex / cell chemotaxis / protein localization to plasma membrane / G protein-coupled receptor activity / intracellular protein transport / adenylate cyclase-activating G protein-coupled receptor signaling pathway / receptor internalization / calcium ion transport / protein transport / heart development / outer membrane-bounded periplasmic space / G alpha (s) signalling events / angiogenesis / periplasmic space / cell surface receptor signaling pathway / lysosome / receptor complex / endosome / G protein-coupled receptor signaling pathway / DNA damage response / cell surface / endoplasmic reticulum / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||
Biological species | Escherichia coli K-12 (bacteria) Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å | ||||||
Authors | Southall, S.M. / Watson, S.P. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: Acs Med.Chem.Lett. / Year: 2022 Title: Novel Macrocyclic Antagonists of the CGRP Receptor Part 2: Stereochemical Inversion Induces an Unprecedented Binding Mode. Authors: Southall, S.M. / Banerjee, J. / Brown, J. / Butkovic, K. / Cansfield, A.D. / Cansfield, J.E. / Congreve, M.S. / Cseke, G. / Deflorian, F. / Hunjadi, M.P. / Hutinec, A. / Inturi, T.K. / ...Authors: Southall, S.M. / Banerjee, J. / Brown, J. / Butkovic, K. / Cansfield, A.D. / Cansfield, J.E. / Congreve, M.S. / Cseke, G. / Deflorian, F. / Hunjadi, M.P. / Hutinec, A. / Inturi, T.K. / Rupcic, R. / Saxty, G. / Watson, S.P. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ax6.cif.gz | 317.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ax6.ent.gz | 209.9 KB | Display | PDB format |
PDBx/mmJSON format | 8ax6.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8ax6_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 8ax6_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 8ax6_validation.xml.gz | 27.6 KB | Display | |
Data in CIF | 8ax6_validation.cif.gz | 41.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ax/8ax6 ftp://data.pdbj.org/pub/pdb/validation_reports/ax/8ax6 | HTTPS FTP |
-Related structure data
Related structure data | 8ax5C 8ax7C 4rwgS S: Starting model for refinement C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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Unit cell |
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-Components
#1: Protein | Mass: 66288.492 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli K-12 (bacteria), (gene. exp.) Homo sapiens (human) Strain: K12 / Gene: malE, b4034, JW3994, RAMP1, CALCRL, CGRPR / Production host: Homo sapiens (human) References: UniProt: P0AEX9, UniProt: O60894, UniProt: Q16602 |
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#2: Polysaccharide | alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose |
#3: Chemical | ChemComp-OP9 / ( |
#4: Chemical | ChemComp-PG4 / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 1.98 Å3/Da / Density % sol: 37.94 % |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, sitting drop Details: 0.1 M BIS-TRIS PH 5.5, 0.1 M AMMONIUM ACETATE, 15 % PEG 10,000 |
-Data collection
Diffraction | Mean temperature: 80 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: Jun 29, 2017 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.96861 Å / Relative weight: 1 |
Reflection | Resolution: 1.9→45.85 Å / Num. obs: 41130 / % possible obs: 96.9 % / Redundancy: 4.1 % / Biso Wilson estimate: 16.52 Å2 / CC1/2: 0.962 / Rpim(I) all: 0.125 / Net I/σ(I): 4.2 |
Reflection shell | Resolution: 1.9→1.94 Å / Num. unique obs: 2554 / CC1/2: 0.536 / Rpim(I) all: 0.508 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4RWG Resolution: 1.9→29.96 Å / SU ML: 0.2322 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 23.5513 Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 28.45 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.9→29.96 Å
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Refine LS restraints |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 12.6665674404 Å / Origin y: -2.94585280184 Å / Origin z: -12.8488802129 Å
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Refinement TLS group | Selection details: all |