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Yorodumi- PDB-6zis: Crystal structure of a CGRP receptor ectodomain heterodimer with ... -
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-Basic information
Entry | Database: PDB / ID: 6zis | |||||||||||||||
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Title | Crystal structure of a CGRP receptor ectodomain heterodimer with bound high affinity inhibitor | |||||||||||||||
Components | Maltose/maltodextrin-binding periplasmic protein,Receptor activity-modifying protein 1,Calcitonin gene-related peptide type 1 receptor | |||||||||||||||
Keywords | MEMBRANE PROTEIN / GPCR / CGRP / CLR / RAMP1 / ECD / COMPLEX | |||||||||||||||
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 (E. coli) Homo sapiens (human) | |||||||||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.73 Å | |||||||||||||||
Authors | Southall, S.M. | |||||||||||||||
Citation | Journal: J.Med.Chem. / Year: 2020 Title: Structure-Based Drug Discovery ofN-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2'-oxo-1',2'- ...Title: Structure-Based Drug Discovery ofN-((R)-3-(7-Methyl-1H-indazol-5-yl)-1-oxo-1-(((S)-1-oxo-3-(piperidin-4-yl)-1-(4-(pyridin-4-yl)piperazin-1-yl)propan-2-yl)amino)propan-2-yl)-2'-oxo-1',2'-dihydrospiro[piperidine-4,4'-pyrido[2,3-d][1,3]oxazine]-1-carboxamide (HTL22562): A Calcitonin Gene-Related Peptide Receptor Antagonist for Acute Treatment of Migraine. Authors: Bucknell, S.J. / Ator, M.A. / Brown, A.J.H. / Brown, J. / Cansfield, A.D. / Cansfield, J.E. / Christopher, J.A. / Congreve, M. / Cseke, G. / Deflorian, F. / Jones, C.R. / Mason, J.S. / ...Authors: Bucknell, S.J. / Ator, M.A. / Brown, A.J.H. / Brown, J. / Cansfield, A.D. / Cansfield, J.E. / Christopher, J.A. / Congreve, M. / Cseke, G. / Deflorian, F. / Jones, C.R. / Mason, J.S. / O'Brien, M.A. / Ott, G.R. / Pickworth, M. / Southall, S.M. | |||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6zis.cif.gz | 309.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6zis.ent.gz | 203.1 KB | Display | PDB format |
PDBx/mmJSON format | 6zis.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6zis_validation.pdf.gz | 456 KB | Display | wwPDB validaton report |
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Full document | 6zis_full_validation.pdf.gz | 462.8 KB | Display | |
Data in XML | 6zis_validation.xml.gz | 24.5 KB | Display | |
Data in CIF | 6zis_validation.cif.gz | 36.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/zi/6zis ftp://data.pdbj.org/pub/pdb/validation_reports/zi/6zis | HTTPS FTP |
-Related structure data
Related structure data | 6zhoC 4rwgS 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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Unit cell |
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-Components
#1: Protein | Mass: 66360.555 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Escherichia coli (strain K12) (bacteria), (gene. exp.) Homo sapiens (human) Strain: K12 / Gene: malE, b4034, JW3994, RAMP1, CALCRL, CGRPR / Production host: Homo sapiens (human) / Strain (production host): HEK293 GNTI References: UniProt: P0AEX9, UniProt: O60894, UniProt: Q16602, UniProt: A0A4P1LXE0*PLUS | ||||||
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#2: Polysaccharide | alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose / alpha-maltose | ||||||
#3: Chemical | #4: Chemical | ChemComp-3N6 / | #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: 2.13 Å3/Da / Density % sol: 42.28 % |
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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: 88 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: Dec 13, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.96861 Å / Relative weight: 1 |
Reflection | Resolution: 1.73→76.98 Å / Num. obs: 57024 / % possible obs: 100 % / Redundancy: 7.6 % / Biso Wilson estimate: 27.75 Å2 / CC1/2: 0.992 / Net I/σ(I): 6.3 |
Reflection shell | Resolution: 1.73→1.77 Å / Redundancy: 7.8 % / Num. unique obs: 4154 / CC1/2: 0.427 / % possible all: 100 |
-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4RWG Resolution: 1.73→57.62 Å / SU ML: 0.2573 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 27.1794 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: 35.4 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 1.73→57.62 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: 12.4819168082 Å / Origin y: -2.19583359294 Å / Origin z: -12.795661097 Å
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Refinement TLS group | Selection details: all |